Medical Biology Course Content PDF

Medical University of Lodz Chair of Biology and Medical Microbiology Department of Biomedicine and Genetics MEDICAL BIOLOGY COURSE COUNTENT FOR MEDICAL STUDENTS 6thyear Medical Division 2023-2024 Medical Ecology PART I Edited by: Ewa Brzeziańskia-Lasota, Katarzyna Khalid Authors: Ewa Brzeziańska-Las...

Medical University of Lodz Chair of Biology and Medical Microbiology Department of Biomedicine and Genetics MEDICAL BIOLOGY COURSE COUNTENT FOR MEDICAL STUDENTS 6thyear Medical Division 2023-2024 Medical Ecology PART I Edited by: Ewa Brzeziańskia-Lasota, Katarzyna Khalid Authors: Ewa Brzeziańska-Lasota, Prof. ScD Katarzyna Góralska, PhD Katarzyna Khalid, PhD Justyna Kiszałkiewicz, PhD Barbara Modrzewska, PhD Anna Wójcik, PhD Karolina H. Czarnecka-Chrebelska, PhD 3 Part I Medical Ecology with elements of Parasitology and Mycology Exercise 1. Homeostasis in the human organism – regulation systems. Abiotic factors. Glossary Abiotic factors – environmental chemical and physical factors such as temperature, soil composition, climate, along with the amount of sunlight, topographic factors (terrain), water, salinity (mineral salt composition), radiation, etc. Anthroposphere - the sphere of the earth system or its subsystems, where human activities constitute a significant source of change through the use and subsequent transformation of natural resources, as well as through the deposition of waste and emission of pollutants. Biosphere – the zone of life on Earth; an area of the globe inhabited by organisms in which ecological processes take place; the global ecosystem, the worldwide sum of all ecosystems; comprises three spheres: the lithosphere (the solid surface layer of the Earth), the atmosphere (the layer of air that extends over the lithosphere), and the hydrosphere (the waters of the Earth - on the surface, in the ground and the air). Biotic factors – environmental factors - any living component that affects another organism (predators, symbionts, parasites, others macro and micro pathogens), or shapes the ecosystem (produce chemical substances, e.g. toxins, or have mechanical, and other effects). Biocenosis (= community) – a group of populations living together in a specific region, in an abiotic environment (called a biotope). Control Centre or Integration Centre – an element of the regulation system in organism, that receives and processes information from the receptor. Effector – an element of the regulation system responding to the commands of the control centre by either opposing or enhancing the stimulus. Ecosystem – a functional ecological unit composed of biocenosis and the environment (biotope); a dynamic and complex whole is not entirely isolated from surrounding units but interacting with them; it is a functional unit in the equilibrium (homeostasis), characterized by energy flow and matter circulation. Homeostasis – stability, balance or equilibrium Negative Feedback – the system’s response aimed at reversing the direction of change Positive Feedback – the system's response aimed at amplifying the change in the variable Receptor – an element of the regulation system that receives information about changes in the environment (internal or external). Population – a group of individuals of the same species, living in a geographic area, in the same region and time; are capable of interbreeding. Ontocenosis – a group of organisms living together on another organism or within human organs. Succession – development and change of an ecosystem over time: a directional and predictable community development process involves changes in the species composition and community processes over time. Ecology (Gr. oikos = home, logos=science) – the branch of biology concerned with the relationship between an organism or a group of organisms and other living things forming food chains (biotic components: producers = autotrophs; consumers = heterotrophs: herbivores, carnivores, omnivores; decomposers – heterotrophs: saprobionts, detritiovores, decomposers, scavengers) and their environment (abiotic factors or conditions). The concept and name “ecology” was introduced by Ernst Haeckel (1866). Nowadays, when defining ecology we should emphasize the influence of organisms on their environment. By definition, the environment means a part of surrounding conditions influencing the natality and survival of organisms. It is essential from the perspective of a modern man who is an element of the biosphere and is also changing the biosphere. Human ecology is an interdisciplinary science. It deals with dynamic biological and social processes between men (individuals, populations and societies) and their environment – natural (biosphere), social (sociosphere), technical (technosphere) and also cultural (noosphere). Medical ecology is a part of human ecology. It focus on the influence of environmental conditions and industrial factors on human organism, mainly in the context of the anthropopression and negative impact of the destroyed and devastated environment on human’s health. In each ecosystem, environmental factors (biotic and abiotic) determine a species' population's range (area of distribution). The presence of organisms and their life functions depend on a set of conditions that may exceed the limits of tolerance defined by V. E. Shelford`s Law of Tolerance (1910). – the eistence of organisms is determined by two values, the so-called extremes of the acting factor: minimum and maximum; the range between the two values is called the tolerance range. This rule was developed based on the Justus Liebig`s Law of the Minimum (1840): an organism must have minimum required amounts of essential materials to grow and reproduce. Due to the multiplicity of the affecting factors, the organisms often do not live in the central or optimal part of the range for all factors. The organism's tolerance for one factor depends on age (developmental stage) and sex, and can be changed by different intensity of other factors. The ecological tolerance limits are usually wider for survival than for reproduction. Individuals in the population may show differentiation for the preferred values of the factors. The environmental factors impacting humans come from the biosphere, technosphere and sociosphere. Some factors as magnetism, gravitation and cosmic radiation are beyond human control. However, they play a role in the physiological processes or functions of the organism. Biological systems like the human body are open systems based on the free exchange of energy and matter with the environment. They are subjected to a continuous influence of various external environmental factors: 1) physical (e.g. temperature, noise, vibration, electromagnetic field, industrial dust); 2) chemical (e.g. CO2, NO2 contained in the air, inorganic ions present in food); 3) biological (e.g. etiological factors of infectious and invasive diseases, toxic substances of plant and animal origin, mycotoxins). However, even with significant fluctuations in the environmental conditions, the organism/human body retains its individuality as a biological unit owing to the mutual cooperation of cells, tissues, organs and systems and appropriate regulatory mechanisms. The metabolic processes of all organisms can only take place in particular physical and chemical environments. Every organism needs a constant composition of the "internal environment", especially concerning the temperature, pH, osmolality, concentrations of mineral ions (e.g. sodium, potassium, magnesium), and numerous chemical compounds (e.g. glucose, carbon dioxide, oxygen). The internal physical and chemical conditions necessary for the optimal function of an organism are in the dynamic state of equilibrium maintained by many regulatory mechanisms. The concept of the internal environment regulation was described by a French physiologist Claude Bernard in 1865, and in 1926 the word homeostasis (homeo- and -stasis = "similar" and "standing still") was coined by Walter Bradford Cannon. Homeostasis is any self-regulating process (regulation of internal conditions inside cells/ organisms) by which biological systems tend to maintain stability while adjusting to optimal conditions for survival. The body attempts to maintain a constant internal environment. The system seeks a dynamic equilibrium, and it tends to reach a steady-state, a balance that resists outside forces of change. When such a system is disturbed, built-in regulatory devices respond to the departures to establish a new equilibrium. Maintaining a stable internal environment requires constant monitoring and adjustments as conditions change. The nervous and endocrine systems mediate all integration processes and coordination of functions. Processing and transfer of information All changes occurring both in the external and internal environment of a human being are received by receptors that process the data and transmit it in an analogue, digital or a mixed manner. Analog transmission Processing and a subsequent transfer of information in a continuous (analogue) way occurs via hormones. From an organ, constituting a signal generator, e.g. the endocrine gland, a chemical compound (hormone - in a given concentration) is transmitted in the blood to other organs affected by it. Example - the influence of the duodenum on the pancreas: 1. stimulus - sour food contents in the duodenum; 2. secretory cell of the mucous membrane (secretion of secretin); 3. secretin circulating in the blood; 4. pancreas (exocrine) stimulated by secretin; 5. pancreatic juice (the amount of pancreatic juice secreted per unit of time is proportional to the circulating concentration of secretin in the blood). Digital transmission The nerve fibres process and transfer the information digitally (stepwise, impulsive). The receptors process the information received from the external environment or the body's internal environment into impulses conducted through nerve fibres. The information is coded in the frequency with which the impulses are guided through the nerve fibre. Example - generating a nerve impulse as a result of a mechanical stimulus: 1. stimulus - pressure on the skin; 2. receptor - lamellar bodies (Pacini bodies) in the skin; 3. afferent nerve impulses; 4. the body of the nerve cell; 5. efferent nerve impulses → effector. Analogue-digital transmission The processing and subsequent transfer of information in an analogue-digital manner occur when the received analogue information is converted into digital in the form of changes in the electrical potential of the neuronal membrane. The same cell subsequently sends the digital information to other nerve cells. Example - the stimulation of vasopressin secretion by increasing the osmotic pressure of the plasma: a. stimulus – an increase in the plasma osmotic pressure (depending on a concentration of the solute particles); b. osmodetector → nerve impulses (hypothalamic osmoreceptors = neurons send impulses via neural afferents to the posterior pituitary); c. stimulation of a neuro-secretory neuron; d. nerve impulses → exocytosis (release) of vasopressin; e. vasopressin circulating in the blood (the amount of vasopressin depends on stimulation of neurons). Maintaining homeostasis is possible due to the presence of effective regulators, restoring the proper functions of cells, tissues, organs and systems. The control process requires information flow: 1) from the control (regulating) system to the controlled (regulated) system - unidirectional information flow (control in the open control system, Fig. 1) 2) from the control system to the controlled system, and then back, from the controlled system to the control system - feedback signal (the closed control system, Fig. 2). control (regulating) system controlled (regulated) system Figure.1. Diagram of the unidirectional information flow (control in the open control system). R – control (regulating) system Ur – controlled (regulated) system Sr – regulated signal Figure.2. Diagram of a closed control system - circulation of signals in the feedback loop. Homeostatic regulation involves three elements: 1) the sensory receptor or detector, 2) the control centre (integration centre or comparator), 3) the effector (effector organ(s)). The receptor receives information that something in the environment is changing. Then, a neuron or hormone (in endocrine mechanisms) transmits information from the sensor to the integration centre (the afferent pathway). The control centre receives and processes information from the receptor. And, by the efferent pathway, information is passing from the integration centre to the effector organs. The effector responds to the commands by either opposing or enhancing the stimulus. This is an on-going process that continually works to restore and maintain homeostasis. The internal and external environment of the body are constantly changing so adjustments must be made continuously to stay at or near the set point (norm values, norm range, the physiological value which fluctuates around the norm range. Disturbance Comparator (reference point) Error signal Effector Controlled variable Sensor Figure. 3. Feedback loop in control system. Adjustment system (homeostatic regulation) Most of the physiological processes in the human body are regulated by feedback, creating the so-called closed regulation loops. The closed control system is a real system that maintains the set value regardless of the environmental factors (Fig. 4). The comparator (Σ) compares the variable value of the parameter (sr) coming out of the controlled system (Ur) with the set level of regulation (so– norm signal = set point = norm value). As a result of this process, information (sb – error signal) is sent to regulators (r) to trigger an appropriate action and a corresponding effect on the monitored element (Ur). R – control (regulating) system Ur – controlled (regulated) system Sr – regulated signal Sb – error signal so– norm signal (set point, norm value) r – regulators Σ - comparator Figure 4. Diagram of a closed control system. When a change of variable occurs, the error signal is generated: the difference between the norm value (norm signal = target value) and the value of regulated signal. There are two main types of possible changes in the internal state of a system – feedback – to which the system reacts: Negative feedback: a reaction in which the system responds in such a way as to reverse the direction of change – minimization of the error signal: so + (-sr) = sb so– norm signal (set point, norm value) sr – regulated signal, sb – error signal, Figure. 5. The minimization of the error signal in the negative feedback loop. Since such a mechanism tends to keep things constant, it allows the maintenance of homeostasis. For instance, when the concentration of carbon dioxide in the human body increases, the lungs are signalled to increase their activity and expel more carbon dioxide. Thermoregulation is another example of negative feedback. When body temperature rises (or falls), receptors in the skin and the hypothalamus sense a change, triggering a command from the brain. This command, in turn, effects the correct response, in this case a decrease in body temperature (or a rise). Positive feedback: a response is to amplify the change in the variable; the error signal is rising – the summing up target value and error signal value is observed: so + s r = s b It exerts a destabilizing effect, so does not result in homeostasis. Positive feedback is less common in naturally occurring systems than negative feedback, but it has its applications. Figure. 6. The increase of the error signal in the positive feedback loop. Sustainable systems require combinations of both kinds of feedback. Regulation based on a positive feedback occurs rarely in the human physiological state and if it works, it only works for a short period of time. For example, in nerves, a threshold electric potential triggers generation of a much larger action potential. Blood clotting, activation of zymogens (proenzymes) in the digestive tract (e.g. pepsinogen into pepsin in the stomach, trypsinogen into trypsin in the duodenum) and events in childbirth are other types of positive feedback. That regulation is often in pathological states. In pathological conditions, negative feedback may be converted into a positive one, which disrupts homeostasis. Thus, the so-called vicious circle occurs. It is a very common pathophysiological mechanism of many diseases (e.g. arterial hypertension, schizophrenia) and addictions (alcoholism, drug abuse). Unstable control system Control mechanisms based on positive feedback usually lead to a system instability. An increasing deviation causes an avalanche reaction resulting in the destruction of the system. A model of this regulation type may be the chemical structure - the “Traube cell”, which is formed as a result of the dissolution of potassium ferrocyanide crystals in a solution of copper sulphate (CuSO 4). Following the reaction of Cu+2 ions and ferrocyanide ions from the crystal (K4 [Fe (CN)6] + 2CuSO4 Cu2 [Fe (CN)6] + 2K2SO4), copper ferrocyanide forms a semipermeable membrane. As a result of the difference in ions concentrations on both sides of the membrane, water enters from the hypotonic external environment into the hypertonic internal environment of the structure, increasing the pressure on the membrane, which, when bursting, releases more ferrocyanide ions, and a new membrane fragment is created. The mechanism causes the “Traube cell” to "grow" until the system disintegrates with the dissolution of the whole crystal. Examples of negative feedback in mammals: Thermoregulation: the average body core temperature hovers around 37 °C (98.6 °F), but several factors can affect this value (hormones, metabolic rate, disease). The hypothalamus in the brain regulates body temperature. The information about body temperature is transmitted through the bloodstream to the brain, resulting in adjustments (feedback), e.g., breathing rate, blood sugar levels, and metabolic rate. The loss of heat occurs as a result of blood circulation in the outer shell of the body, evaporation from the epidermis and sweating. It is reduced by decreased circulation to the skin (contraction of smooth muscles in the blood vessel wall), insulation by subcutaneous fat, clothing and external heat sources. The skeletal muscles can shiver to produce heat if the body temperature is too low. Nonshivering thermogenesis involves the decomposition of fat to produce heat. Fever occurs when body's core temperature rises above the normal steady-state levels, and the body reacts as if it is too cold. Fever implies a disorder resulting in shivering accompanied by vasoconstriction, headache, and general discomfort. Environment z1 sb(+) Fat tissue sb(+) Skeletal muscles sb(+) Liver S0 Σ sb(+ ) sb(+ ) s b Skin blood vessels Respiratory system Sweat glands z2 S1 S2 S3 S4 S5 S6 Sr Internal body temperature Sr – regulated signal Sb – error signal So– norm signal (set point, norm value) S1, S2, … – regulating signals Z1, Z2 - interfering signals Σ – comparator Figure 7. The human body temperature regulation. The tight control of its blood glucose concentration is needed to ensure the normal function of the human body. This is accomplished by a network of various hormones and neuropeptides released mainly from the brain (hypothalamus), pancreas, liver, intestine as well as adipose and muscle tissue. A key place within this network represents the pancreas by secreting the blood sugar-lowering hormone insulin and its opponent hormone glucagon. Insulin promotes the conversion of glucose into glycogen stored in the liver till glucose is needed later. Glucagon stimulates the conversion of glycogen into glucose. Dysglycemia – an abnormality in blood sugar stabilitycan include hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar). It can be caused by various conditions, including: diabetes (type 1 due to autoimmune β-cell destruction and type 2 due to a progressive loss of β-cell insulin secretion), gestational diabetes mellitus (GDM), pre-diabetes, endocrine disorders (e.g. adrenal gland deficiency), tumours that produce excess insulin, eating disorders (e.g. anorexia) or malnutrition. Dysglycemia can also result from infections, impaired immune function, genetic syndromes accompanying diabetes, and not adequately used drugs (including diabetic medications). Table 1. Diagnostic criteria for dysglycemia: Random blood glucose — measured in a blood sample collected at any time of the day, regardless of the timing of the last meal ≥ 200 mg/dL (≥ 11.1 mmol/L) → diabetes* (if symptoms of hyperglycemia are present, e.g. increased thirst, polyuria, fatigue) Fasting blood glucose — measured in a blood sample collected 8–14 hours after the last meal Venous plasma glucose level 70–99 mg/dL (3.9–5.5 mmol/L) → normal glucose tolerance (NGT) 100–125 mg/dL (5.6–6.9 mmol/L) → impaired fasting glucose (IFG) ≥ 126 mg/dL (≥ 7.0 mmol/L) → diabetes* Blood glucose at 120 minutes during an oral glucose tolerance test (OGTT) according to WHO < 140 mg/dL (7.8 mmol/L) → normal glucose tolerance (NGT) 140–199 mg/dL (7.8–11.0 mmol/L) → impaired glucose tolerance (IGT) ≥ 200 mg/dL (≥ 11.1 mmol/L) → diabetes* WHO — World Health Organization; *Diagnosis of diabetes requires one abnormal reading, except for fasting blood glucose which requires two abnormal readings. A potential effect of factors not related to testing itself should be taken into account when measuring blood glucose (timing of the last meal, exercise, time of the day) Environment Z1 sb(+) pituitary gland sb(+) thyroid sb(+) adrenal cortex sb(+) sb(+) C0 Σ sb(-) adrenal medulla α-pancreatic cells β-pancreatic cells Z2 somatotropin triiodothyronine T3, thyroxine T4 glucocorticoids adrenalin glucagon insulin sr glucose concentration Sr – regulated signal Sb – error signal co– norm signal (set point, norm value) Z1, Z2 - interfering signals Σ – comparator Figure 8. The regulation of blood glucose concentration in human body. The regulation of blood pH: the lungs take in oxygen and give off carbon dioxide, regulating pH in the blood. The kidneys adjust the concentrations of bicarbonate ions and can generate new HCO3 when it is low. To keep the human body alive, blood pH should be between 7.35 and 7.45; pH < 7.35 is called acidosis and pH > 7.45 is alkalosis. The optimal blood pH is 7.4. Blood pH below 6.9 and above 7.9 is usually fatal if it remains at these levels more prolonged than a short while only. Normal metabolism produces large amounts of CO 2 (a by-product of the oxidation process in cells/tissues) continuously (about 14 moles/day). If the CO2 was not removed, we would rapidly develop fatal acidosis. In the human body, there are buffers responsible for maintening blood pH. The basic buffers and their percentage participation in buffering capacity are as follows: bicarbonate – 70%, haemoglobin – 21%, albuminate – 6%, phosphate – 3%. Osmoregulation: the regulation of the amounts of water and minerals in the blood / in the body. The kidneys are organs of the urinary system which removes excess water, wide variety of mineral ions and urea, maintaining the correct concentrations of water and ions. Examples of positive feedback in physiological conditions: Blood clotting - in the case of a vessel injury, the coagulation cascade starts the series of biochemical reactions in which an inactive precursor is activated to become an active component. This subsequently catalyses the next clotting factor in the cascade (several factors are gradually activated in a specific order), ultimately resulting in cross-linked fibrin; owing to the appropriate enzymes, the catalytic reactions accelerate and increase at particular stages of coagulation. Childbirth - a childbirth, once begun, must progress rapidly to a conclusion, or the life of the mother and the baby is at risk. It starts when the head of the baby pushes against the cervix. The stretch-sensitive nerve cells that monitor the degree of stretching (the sensors) send messages to the brain, which causes the pituitary gland of the brain to release the hormone oxytocin into the bloodstream. Oxytocin triggers stronger contractions of the smooth muscles in the uterus (the effectors), pushing the baby further down the birth canal. It makes the cervix stretch even more. The cycle of stretching, oxytocin release, and increasingly powerful contractions stops once the baby is born. At this point, the stretching of the cervix stops, blocking the release of oxytocin. Ultrastable regulation system Due to physiological regulations in the long-term periods, the body adapts to the changing conditions of the surrounding environment. From the point of view of human adaptation, the body can be treated as an ultrastable system able to ensure optimal self-regulation and adaptation to new environmental conditions (Figure 10). The control system also includes an adaptive system (memory converter) that allows the comparator to be tuned to a new level (changing the setting value of a specific parameter) due to repeated exposure to various environmental and / or intrinsic factors. This phenomenon may be illustrated by the consequences of long-lasting endurance training which in athletes leads to a decrease in the frequency of heart contractions in resting conditions. Resting bradycardia, in which the number of heart contractions does not exceed 50 beats per minute (resting, physiological heart rhythm in a non-trained person - approx. 70 beats / min.), results of increased resting tension of the parasympathetic nervous system (vagus nerve) and physiological hypertrophy of the heart (athlete's heart). R – control (regulating) system Ur – controlled (regulated) system sr – regulated signal sd – error signal so– norm signal (set point, norm value) s – regulating signal r – regulators Σ – comparator A - adaptive system (memory converter) Figure 9. Diagram of an ultra-stable regulation system. Methods for assessing efficiency of the regulation system The efficiency of systems regulating specific parameters of the human body (maintaining homeostasis) is assessed after inducing a disturbance of a given parameter (disturbance in the equilibrium state) and then evaluating: regulating system response time (rate of regulation system’s action) from the moment the factor disturbing homeostasis appears until the value of parameter subject to regulation is changed); the most significant deviation of the value of the regulated parameter as compared to its balance value; the return time of regulated variable value to the target value (norm range) after knocking out from the equilibrium state. The systems' efficiency may be evaluated through load tests (e.g. blood glucose concentration regulation - oral glucose tolerance test (OGTT), effort - exercise test for the cardiovascular system evaluation). The assessment of cardiovascular fitness and its adaptability to various physical activity conditions has practical medical significance. For this purpose, specific load conditions are created (physical effort with the use of exercise treadmill/bike, with recording the electrical activity of heart -exercise tolerance testing ETT) and an evaluation is made focused on cardiovascular function indicators reaction, e.g., heart rate, blood pressure, stroke volume (SV) and cardiac output (CO), the electrical activity of the myocardium (electrocardiogram ECG). Exercise tolerance testing (ETT) is one of the methods used to determine the presence of significant coronary heart disease. But it does not show 100% sensitivity and specificity. For this reason, ETT is assisted or replaced by cardiac imaging techniques, such as myocardial perfusion scanning (also referred to as myocardial perfusion imaging MPI or MPS). Physical effort increases the heart rate, systolic pressure, blood ejected by the myocardium, increased blood flow through the heart, muscles and skin. A dynamic blood flow increases the production of CO 2 and H+ ions in the tissues, which requires greater oxygenation. Faster and deeper breaths provide more oxygen. However, strenuous physical exertion cannot compensate for the oxygen demand of the tissues, leading to hypoxia (tissue hypoxia). In the case of excessive muscular activity, the cells are switched to anaerobic respiration, which promotes the lactic acid production (muscle acidosis). The acid formed in the muscles when training is quickly removed from them. Only one or two hours after the exercise, lactic acid in the form of lactate goes to the liver and is converted into glucose and then into ATP. The effort test (exercise test) evaluates two elements: aerobic fitness - VO2 max, MET; exercise tolerance. Physical fitness (physical efficiency, physical capacity) is a set of properties / attributes that people have or achieve and which determine their ability to do physical activity. Physical fitness is the body's ability to respond or adapt to the requirements and stress associated with physical exertion; it is the ability to undertake heavy or prolonged physical activity involving large muscle groups, without major changes in homeostasis. Physical fitness is genetically determined and depends on somatic (skeletomuscular, cardio-respiratory, hematocirculatory, endocrine-metabolic) factors. Additionally, it is subject to training and also depends on individual characteristics (psycho-neurological factors, motivation). The indicator of the human physical efficiency is aerobic capacity, which is most often referred to as the maximum oxygen absorption VO2 max (oxygen VO2 max, the amount of oxygen consumed in 1 minute, the maximum minute oxygen uptake, peak oxygen uptake,maximal aerobic capacity, metabolic equivalent). Maximal oxygen consumption reflects cardiorespiratory fitness and endurance capacity in exercise performance; it is the ability to perform long-term efforts without any significant increase in fatigue and is usually measured as the oxygen uptake in the lungs. A resting oxygen consumption of 3.5 ml / kg / min is marked as 1 MET (metabolic unit). The number of MET for a given type of physical exercise shows how many times more energy will be used for exercise than at rest (3-6 MET = moderate intensity daily activities, cycling at a speed of 15-18 km / h = 6 MET, running (12 km / h) - 12 MET). The more oxygen the body takes, the more energy it can produce; this fact is of great importance in endurance sports. Physical anaerobic capacity is associated with short intensive work lasting 30-60 seconds (the cardiovascular system does not keep up with the supply of oxygen to the muscles - there is the so-called anaerobic burning = anaerobic glycolysis). Exercise tolerance is the ability to exercise without significant disturbances of homeostasis or changes in the functions of the internal organs. The measure of exercise tolerance is the time of performing work of a specific intensity level / load size before reaching a state of exhaustion (e.g. coronary pain, dyspnoea, cyanosis, balance disorders, dizziness, lowering the ST segment in the ECG, arrhythmias, exercise hypertonia). Exercise tolerance tests are commonly performed on a treadmill under the supervision of a health professional who can stop the test if signs of distress are observed. Exercise tolerance tests (ETT) Evaluation of heart work (changes in the blood pressure and heart rate, electrocardiography ECG) during exercise and an increased oxygen demand can be carried out applying the following tests: static - squeezing the dynamometer with the dominant hand at a given value of maximum voluntary contraction (MVC) and holding it, e.g. for 3 minutes; dynamic - without the possibility of determining the maximum oxygen consumption - a Ruffier test, a Master’s test, a test on a treadmill or an exercise bike; dynamic - using direct and indirect methods to determine the maximum oxygen consumption (on a treadmill or an exercise bike). Biological systems like the human body are subjected to various external abiotic environmental influenses, among others physical factors: e.g temperature, noise, vibration, electromagnetic field, industrial dust); Among abiotic factors, the physical factors - the temperature and presence of water - are essential for organisms affecting the distribution of species. Temperature Temperature exerts an essential influence on living organisms – few can survive at temperatures below 0 °C (32 °F) due to metabolic constraints. It is also infrequent for most organisms to survive at temperatures exceeding 45 °C (113 °F). Enzymes are most efficient within a narrow and specific range of temperatures; at higher temperatures enzyme degradation may occur (protein denaturation). Therefore, organisms must either maintain an internal temperature or inhabit an environment that will keep the body within a temperature range that supports metabolism. Some organisms have adapted to survive significant temperature fluctuations, e.g. some bacteria have adapted to survive in extremely-hot temperatures occurring in places such as geysers (thermophilic archeons Pyrolobus fumarii – survive in 113°C). Such bacteria are examples of extremophiles: organisms that thrive in extreme environments. Two groups of animals may be distinguished: poikilotherms (heterotherms) – animals (cold-blooded animals: fishes, amphibians, reptiles and invertebrate animals) whose internal temperature differs considerably as a consequence of variation in the ambient environmental temperature, and homeotherms (homoiotherms, warm-blooded: all mammals and birds and some species in the other classes of animals) – those which maintain a stable temperature (thermal homeostasis). In heterothermic animals, the metabolism intensity grows or decreases with a rise or drop in temperature. Frequently, the relation corresponds to van`t Hoff’s rule: the change of temperature by 10° causes a twofold to threefold change in the metabolism’s intensity (experiment with Daphnia sp. – changes in the heart rate depending on the temperature). Some animals have adapted to survive significant temperature fluctuations – in unfavourable thermal conditions they enter a state called hibernation, estivation, or torpor. Torpor is a state of a decreased physiological activity in an animal, usually by a reduced body temperature and metabolic rate. Torpor enables animals to survive periods of reduced food availability and may last less than 24 hours, both at night and during the day, depending on a feeding pattern of the animal (as in "daily torpor" - some birds, rodent species such as mice, and bats). Long periods of inactivity, with a reduced body temperature and metabolism (saving the energy), including multiple bouts of torpor are known as hibernation or estivation. Hibernation, lasting days to weeks, is a state of dormancy observed in rodents or bears. Before entering the hibernation stage, animals generally store fat to help them survive the long winter. During hibernation, they may wake up for brief periods to eat, drink, or defecate; however, for the most part, hibernators remain in this low-energy state for as long as possible. Estivation allows animals to survive in a hot, dry climate. Many animals, both invertebrates and vertebrates, use this tactic to stay cool and prevent desiccation when temperatures are high and low water levels. Animals that estivate include molluscs, crabs, mosquitos, many reptiles and amphibians (crocodiles, some salamanders, desert tortoises), also fish and mammals (the dwarf lemur, hedgehogs). Some organisms have antifreeze-like substances in their cells, which help retain the integrity of cells and prevent them from bursting, e.g. glycerol or dimethyl sulfoxide in insects, glycerol or trehalose in other invertebrates (nematodes, rotifers), proteins in Antarctic fishes. Most humans will suffer hyperthermia after 10 minutes in extremely humid, 60º Celsius (140º Fahrenheit) heat. Death by cold is usually observed when human body temperature drops to 21ºC (70ºF). The atria and ventricles of the human heart stop communicating below 27°C (80.6°F), and below 20°C (68°F), the myocardium may stop beating completely. Mild hypothermia (32–35°C body temperature) may be easy to treat. However, the risk of death increases as the core body temperature drops below 32°C. Similarly, temperature lower than 28°C is life-threatening without immediate medical attention. Normal human body temperature, also known as normothermia or euthermia, is the typical temperature found in humans and usually ranges from 36.5 to 37.5 °C (97.7–99.5 °F). Hypothermia < 35.0°C (95.0°F) Normal 36.5–37.5°C (97.7–99.5°F) Fever > 37.5 or 38.3°C (99.5 or 100.9°F) Hyperthermia > 37.5 or 38.3°C (99.5 or 100.9°F) Hyperpyrexia > 40.0 or 41.0°C (104.0 or 105.8°F) People can live indefinitely in environments that range between roughly 40º F and 95º F (4º C and 35º C), if the latter temperature occurs at no more than 50 per cent relative humidity (1958 NASA report). The maximum temperature pushes upward when it is less humid, because lower water content in the air makes it easier to sweat, and thus, keep cool. Low temperatures change the speed of different chemical reactions, disturbing the equilibrium of delicately balanced systems. Human cell cultures can be frozen and thawed, even though some of the cells will die. “Biological zero” is the temperature in which the vital functions of organs, tissues or cells are inhibited (e.g. for lymphocytes – 6°C, neurons – 5-12°C). Temperatures above the tolerance limits are a factors restraining a microorganism’s growth: sterilization and disinfection. Sterilization is a process that kills all living organisms, including spores. It may be achieved by the use of:  burning out (the scalpel, loop) in the gas burner fire;  dry heat at 160°C for 1 hour or 140°C for 3 hours;  autoclavation (autoclaving): saturated steamat temperature 121-123°C (250°F) with pressure 150 kPa (1.5 atm) for 30 minutes;  tyndalization: the fractionate pasteurization 3 times, every 24 hours;  UHT ultra-high temperature processing (ultra-heat treatment or ultra-pasteurization) – a food processing technology that sterilizes liquid food by heating it above 135°C (275°F) – the temperature required to kill spores – for 2 to 5 seconds. UHT treatment is most commonly used in milk production (first developed in the 1960s, temp. 135-150°C ), but the process is also used for fruit juices, cream, soy milk, yoghurt, wine, soups, honey, and some meat and vegetables dishes. Chemical factors that are used include, among others, glutaraldehyde and ethylene oxide gas (for plastics). In contrast, physical factors are UV-radiation, ionizing-radiation, ultrasounds or filtration (first there were filter candles made of diatomaceous earth, now cellulose nitrate or cellulose acetate filters with 0.1 to 0.2 μm diameter pores). Disinfection is a process that kills vegetative microorganisms forms, but does not kill spores:  boiling in the water of 100°C (212 °F) for 15-30 minutes or using steam at a temperature of 100°C for some instruments, clothes, bedclothes, blankets etc.;  pasteurization - a hot-treatment process, well below the boiling point, which destroys all harmful microorganisms and improves the quality of food;e.g. for milk: temperatures of about 63 °C (145 °F) for 30 minutes or, 72 °C (162°F), for 15 seconds;  chemical disinfection - may be achieved by using e.g. chloramine, chlorhexidine, iodophors, ethanol, quaternary ammonium compounds; different disinfectants have different target ranges. Not all disinfectants can kill all microorganisms. Decontamination is the process of removing pathogenic microorganisms from the articles by a process of sterilization or disinfection. It uses physical or chemical means to remove, inactivate, or destroy living organisms on a surface so that the organisms are no longer infectious. Sanitization is the process of chemical or mechanical cleansing applied in public health systems. It reduces microbes found on eating utensils to safe levels acceptable for public health. The food industry most frequently uses it. Asepsis is the absence of infectious material or infection; it employs various techniques (such as usage of gloves, air filters, UV rays etc.) to achieve a microbe-free environment. Surgical asepsis is the absence of all microorganisms within any invasive procedure. Antisepsis uses of chemicals (antiseptics) to make skin or mucus membranes devoid of pathogenic microorganisms. Water is an essential condition for life. Organisms differ in adaptation to changes of water contents in the environment or to lose water by own structures, e.g. death is caused by approximately a 20% loss in humans and by some 95-97% of water loss in Tardigrade (“water bears” or “moss piglets”; the group of animals of 0.1 – 1 mm length, with no defined systematic position, sometimes classified as a group of arthropods; their body is cylinder in shape with four pairs of short mamilliform, not divided limbs with claws). Tardigrades can survive also in extreme temperatures: a few minutes in 151°C (304°F), 30 years in −20°C (−4°F), a few days in the temperature of −200°C (−328°F; 73 K), a few minutes in −272°C (−458°F; 1 K) and can withstand 1.000 times more radiation than other animals. Anabiosis (Gr. anabiosis = reviving, livening up; vita minima, cryptobiosis) may be caused by dehydration without the organism’s protein colloidal system destruction. In this process, certain animals (e.g. many Protozoa, Tardigrada, Rotatoria – from Nemathelminthes) faced with severe dehydration (anhydrobiosis) can enter a state of hibernation and survive without any water for long periods of time. Rehydration can lead to their revitalization to a normally lively specimen within half an hour. Freeze drying is the dehydration method where quick freezing in temperature range from –30°C to –70°C with reduced pressure is used (the process called sublimation - water is evaporated from the ice crystals without melting them). This process allows for a long-term storage of some biological materials: plasma, bacteria, some drugs and some food products. Environmental pollution and closely related food contamination have been significant problems for recent decades. They have a profound impact on human health. Some pollutants in the biosphere are xenobiotics – substances produced by men previously never found in the biosphere (e.g. dioxins, chloroorganic compounds). The organism may remove xenobiotics by deactivation and excretion. Some xenobiotics substances are resistant to degradation and may accumulate in the environment. Some – may undergo degradation by microorganisms in a method known as bioremediation (a technique used to treat contaminated media – water, soil and subsurface material, by altering environmental conditions to stimulate the growth of microorganisms and degrade the target pollutants). Natural substances and pollutants may exert various acute and/or chronic effects on living organisms, including sensitizing / allergenic, carcinogenic, mutagenic, teratogenic and embryotoxic effects. They may also be harmful to fertility and reproduction. Among environmental (and also occupational) pollutants we distinguish substances abbreviated as CMRsubstances: carcinogenic (C), mutagenic (M) and substances that can be harmful to reproduction (R). Some substances in this group can cause several of the mentioned effects. A carcinogen is a substance, organism or agent that can cause cancer. Most carcinogens work by interacting with a cell’s DNA. As a result, mutations arise and may promote cancer cells in the process of carcionogenesis. Carcinogenesis is a multistage process driven by carcinogen-induced genetic and epigenetic damage in susceptible cells that increase growth and undergo clonal expansion (via activation of protooncogenes and/or inactivation of tumor suppressor genes). Carcinogens may occur naturally in the environment (such as ultraviolet rays in sunlight and certain viruses) or may be caused by human activity harmful to health (such as automobile exhaust fumes, industrial pollution and cigarette smoke).. The identification of physical carcinogens is based on epidemiologic and/or experimental data. The examples of known human carcinogens may be divided into different categories such as: - chemical (asbestos, benzene, benzo[a]pyrene, chromium (VI) compounds, ethanol in alcoholic beverages, formaldehyde, nickel compounds, plutonium, tobacco smoke, vinyl chloride, hard and soft materials includes metals and metallic alloys, synthetic products; - physical (ionizing radiation (X- and Gamma-radiation, cosmic rays, alpha rays, beta rays), ultraviolet (UV) radiation, including UVA, UVB, and UVC rays), - biological (aflatoxins, infection with Epstein-Barr virus (EBV), Clonorchis sinensis (Chinese liver fluke), Helicobacter pylori, Hepatitis B virus (chronic infection), (American Cancer Society, www.cancer.org/cancer/cancer-causes). Environmental agents which cause mutations are known as mutagens. A mutagen is a physical or chemical agent that changes the genetic material, usually DNA, of an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer, mutagens may also be, not always though, carcinogens. A reprotoxic chemical can damage the reproductive process (it is toxic to reproduction).Such substancesmay adversely affect sexual function and fertility in adult males and females, as well as cause developmental toxicity in the offspring. Mutagenic chemicals in food contribute to 35% of cancers. For chemical compounds present in food, quality standards are defined. They are measures of the quantity of a particular compound (organizations responsible for such assessments: Joint FAO/WHO Expert Committee on Food Additives, Joint FAO/WHO Meeting on Pesticide Residues, European Food Safety Authority, US Environmental Protection Agency). The Acceptable Daily Intake (ADI) is an estimate of the amount of an additive in food or beverages expressed in body weight (bw) basis that can be ingested daily over a lifetime without any significant health risk to the consumer (it is expressed as mg/kg body weight per day). The ADI is typically derived from the lowest no-observed-adverse-effect level (NOAEL) determined based on long-term animal (in vivo) studies, i.e. the amount of a substance, that can be fed to animals daily without causing any harmful effects. There is also the lowest-observed-adverse-effect level (LOAEL), i.e. the lowest concentration or amount of a substance (found by experiment or observation) that causes an adverse alteration of morphology, function, capacity, growth, development, or lifespan of a target organism distinguished from normal organisms of the same species (under defined conditions of exposure). The lethal dose - LD (DL -dosis letalis) parameter is used to assess and compare the toxic effects of substances (acute toxicity). The most frequently determined one is the DL50, i.e. a dose of a substance or chemical compound introduced into the body (dose taken) by various routes (through the skin, alimentary way, inhalation) and causing mortality of 50% of the population (Table 2). Radiation The human body can be affected by ionizing and non-ionizing radiation (electromagnetic, e.g. produced by household electrical appliances). Ionizing radiation means all types of radiation that cause ionization of the material medium, by detaching the electron from the atom / particle or its breaking out of the crystal structure. Ionizing radiation can ionize the medium through which it passes directly or indirectly. The biological effect of ionizing radiation depends on: 1. size, dose, type of radiation (ionizing corpuscular: α, β, neutron, proton and ionizing radiation electromagnetic X-rays (X) or (γ); 2. dose rate; 3. amount of irradiated tissue and the type of tissue / organ; 4. biological features (oxygenation of cells is significant ) and the general state of the biological organism. The biological effect of radiation is associated with radiosensitivity (radiationsensitivity). It is the ability of cells and tissues to react to absorbed radiation energy. This property is proportional to the rate of cell division and inversely proportional to the degree of their differentiation (Bergonie and Tribondeau law). Radiosensitivity refers both to an individual and a species. Representatives of lower taxonomic groups are usually more resistant to radiation. The biological effect of ionizing radiation can be considered in the aspect of: - direct effect - revealed in the place of absorption;radiation interacts with the atoms of the DNA molecule, or some other cellular component critical tothe survival of the cell; - indirect effect - radiation effect is not revealed at the absorption site;occurs when radiation interacts with non-critical target cell atoms or molecules, usually water;this results in the production of electrons, H · atoms, ·OH radicals, H3O+ ions and molecules (dihydrogen H2 and hydrogen peroxide H2O2), which then contribute to the destruction of the cell. A wide range of physical and chemical agents can adversely affect the reproductive functions in animals. Teratology (Gr. teratos= monster) studies the structural abnormalities that arise during embryonic development (teratogenesis = from the Greek, meaning monster making). Malformations may occur from errors in genetic programming, environmental agents or factors, or unknown causes. About 7 to 8% of all live births will have congenital disabilities/ abnormalities; 2% of all birth defects are due to prenatal exposure to radiation, environmental chemicals, and drugs; also the biological agents e.g. the Rubella (German measles), Toxoplasma gondii (parasitic protozoan). The abnormalities may be demonstrated as: - aplasia (the loss of an organ or its part), - hypoplasia (incomplete development of a tissue or an organ), - hypertrophy (outgrowth). Congenital defects (malformations) may exist as isolated abnormalities or co-occur in genetic syndromes: - anencephaly - the absence of a significant portion of the brain, skull (acrania) and scalp; - spina bifida - incomplete closing of the spine and membranes around the spinal cord; - cleft lip and/or palate; - syndactyly - merging two or more fingers; - ectrodactyly - limb malformation consisting in the total or partial lack of one or more central digits of the hand or foot; also known as split hand/split foot malformation (“lobster tongs”, "claw-like" fingers) - arachnodactyly (finger spider) - excessively thin and long fingers of the hand; the trait may exist as coexisting, e.g. in the Marfan syndrome or as an isolated feature; - sirenomelia (mermaid syndrome) – deformity in which the legs are fused together, giving the appearance of a mermaid's tail, a fusion of lower limbs; - phocomelia (no closer parts of the limbs); - amelia - lacking one or both limbs. The most common malformations are heart defects and a hernia of the lumbar spine (this defect develops in the first 4 weeks of the embryonic life). It has been shown that a daily intake of 4 mg of folic acid by females, one month before expected fertilization, and then for the first three months of pregnancy, reduces the risk of development of a neural tube defect (NTD) in a child in families with a history of NTD. For 1000 live births, 2-3 children have nervous system defects, and mortality due to these defects reaches 0.89 per 1000 live births. A teratogenic response depends on the administration of a specific agent at a particular dose to a susceptible species during the period when the embryo is in a susceptibles stage of development. There are several essential characteristics of teratogens: - most teratogens cause no obvious abnormality of the chromosomes; thus, most teratogen-induced abnormalities are limited to somatic cells and are not heritable; - teratogens are selectively toxic to the developing organs of the foetus; potent teratogens are neither highly toxic to the mother nor the foetus, since such actions would prevent foetal development and, hence the manifestation of structural abnormalities. For example, for thalidomide, the ratio of the teratogenic dose to the toxic maternal dose is 1:200. - teratogens exhibit stage selectivity – the susceptibility to teratogens varies during gestation: the period of cell proliferation is the initial stage of development; extends from fertilization to early post-implantation (initial 2 weeks of human gestation). During this period, teratogens have an all-or-none effect: the embryo is either affected so severely that it results in death or so few cells are affected that the embryo may replace the lost cells and develop normally. the second stage, the period of organogenesis (3-8 weeks of human gestation), is the period of greatest sensitivity to teratogens. the third stage of development, the foetal period, is relatively insensitive to teratogens, although functional alterations, growth retardation, and foetal death may occur. - teratogens exhibit selectivity in mechanism and site of action; they often produce only a few specific malformations rather than a wide range of organ abnormalities. A given teratogen may induce more than one type of defect and a given defect may be caused by more than one teratogen. - teratogens exhibit dose-response relationships: as the dose increases, the frequency and severity of teratogenic effects increase as well (no effect 1000; the molecular weight of most drugs is 250-400. Mechanism and sites of action: teratogenesis is thought to be caused by disruption of any of the processes involved in organogenesis: proliferation, differentiation, aggregation, migration, and cell death. Cell proliferation occurs throughout the organogenesis period. Differentiation is when genetically identical cells starts to exhibit differing characteristics (phenotypes) due to processes that either activate or inactivate gene expression. Cell migration, cell aggregation (the interaction of different cell groups) and cell loss are required for the latter stages of organogenesis. These processes occur in a highly regulated and orderly manner. Teratogens can interrupt these processes in specific ways that are timedependent. Chemical Teratogens Ethanol – alters the properties of cell membranes. It is thought to exert its teratogenic effects by altering germ layer formation in the developing embryo through a direct impact on cell proliferation. This action occurs at day 17 of human gestation. A cluster of defects, termed the foetal alcohol syndrome (FAS), may be observed in the offspring of mothers who ingest alcohol during this critical period. FAS is characterized by craniofacial abnormalities (microcephaly, small eyes, low nasal bridge, and flat midface); other manifestations include growth retardation, skeletal malformations and cardiovascular abnormalities. Functional impairments include severe mental retardation (50% of offspring), muscle weakness, incoordination, hyperactivity, reduced attention span, speech impairment and hearing deficit. Ethanol is the most frequent cause of drug-induced mental deficiency in the USA. Up to 33% of offspring born to chronic alcoholic women (> 6 ozs.(about 178 ml/day) will manifest FAS. A safe dose of alcohol has not been determined for a pregnant woman and her baby. During pregnancy and lactation, any dose of alcohol is dangerous to the fetus / baby. Alcohol can damage the fetus at any stage of its development. Thalidomide – a sedative-hypnotic drug introduced into clinical practice in West Germany in 1956. It was marketed in 46 countries (but not the USA) to treat nausea associated with morning sickness during pregnancy. By 1959, nearly 10,000 deformities were documented as arising from thalidomide exposure from 3 to 8 weeks of gestation. Recent studies suggest that the mechanism of teratogenic action of thalidomide is a reduction in the expression of cellular adhesion molecules on the surface of cells. Cellular adhesion molecules play a role in cell migration and aggregation. Alteration in the concentration of these molecules at the cell surface could perturb these processes during organogenesis. The major teratogenic effect of thalidomide is dysmelia which is characterized byan absence of a part of the limb (e.g. phocomelia). Other abnormalities include facial haemangioma (highly vascularized benign tumour), oesophageal or duodenal atresia (closure), and abnormalities of the heart, kidneys, and external ears. The teratogenic risk from thalidomide exposure is difficult to estimate since all studies are retrospective. The investigations accomplished in our Department showed the teratogenic effect of Ascaris proteolysis inhibitors. The most frequent defects in mice were the cleft palate, encephalomeningocele, ribs fusion. Also, the teratogenic effect was observed in hen (Gallus sp.) embryos and it was manifested by crossed beak, cyclopia, schistocelia, and nonretracted yolk sac. References: 2. Campbell, J.B. Reece: Biology. Pearson, Benjamin Cummings, Seventh Edition 2005 3. Meder S., Windelspecht M.: Human Biology. McGraw-Hill Science/Engineering/Math, Twelfth Edition 201