Introduction to Human Physiology PDF

**Physiology** explores the science of life by examining the mechanisms of living organisms. It delves into the functions of cells at the ionic and molecular levels, extends to the coordinated activities of the entire body, and considers the impacts of external environmental factors. Multiple organ...

**Physiology** explores the science of life by examining the mechanisms of living organisms. It delves into the functions of cells at the ionic and molecular levels, extends to the coordinated activities of the entire body, and considers the impacts of external environmental factors. Multiple organ systems (heart, kidneys, endocrine glands) all have the effect of maintaining body function around a set point as biological systems become more complex we use reductionist methods to isolate particular processes to aid and understanding however we must not neglect a holistic view of the entire system that recognizes the emergent properties that emanate from the synergies among components. All components work together to maintain a relatively constant internal environment, a process known as **homeostasis**. Homeostasis refers to the dynamic mechanisms that detect and respond to deviations in physiological variables from their set point values, initiating effector responses to restore these variables to their optimal physiological range. **Basic organization of tissues and organs within the human body: Cell division and growth** → **Cell differentiation** → **Specialized cell types** → **Tissues** → **Organ (kidney)** → **Organ system (urinary system)** **Cells** of the body can be categorized into four main functional groups. **Specialized Cell Types and Tissues**: Epithelial cell (Epithelial tissue), Connective-tissue cell (Connective tissue), Neuron (Nervous tissue), Muscle cell (Muscle tissue) The **cell** is the smallest unit capable of maintaining the functions characteristic of life. All **cells** are remarkably similar in how they exchange materials, obtain energy, synthesize organic molecules, duplicate themselves, and detect and respond to **signals** in their immediate environment. **Cells** of an organism all carry the same genome, yet the expression of different parts of this **genome** leads to **cell** differentiation, transforming an unspecialized **cell** into the specialized **cells** that make up the body. As many as 200 different types of **cells** can be identified in the body. These **cells** can be further divided into functional groups, where **cells** share a common theme but vary in their function from **tissue** to tissue. Different tissues are combined into organs, which frequently contain **cells** of all four common themes. **Epithelial cells** are specialized for selective secretion and absorption of ions and organic molecules and for protection. These **cells** are characterized and named according to their unique shapes. For example, **cuboidal** or cube-shaped cells, **columnar** or elongated cells, **squamous** or flattened cells, and **ciliated** cells. **Epithelial cells** form boundary tissues of either a single **cell** layer (simple epithelium) or multiple **cell** layers (stratified epithelium). **Epithelial cells** can also serve as a protective layer for many **organs** and have specialized functions depending on where in the body they are found. **Epithelial cells** rest on an extracellular protein layer called the **basement** membrane, which anchors the tissue. The **cell membrane** facing the **basement membrane** is referred to as the **basolateral** side, and the **cell membrane** facing the interior or lumen is called the **apical** or **luminal** side. A distinguishing feature of these **cells** is that the two sides perform very different physiological functions. In most tissues, **epithelial cells** are connected to one another at their lateral surfaces by an extracellular barrier called **tight** junctions. **Tight junctions** enable **epithelial tissue** to form boundaries between body compartments and to function as a selective barrier regulating the passage of materials. For example, **glucose** is actively removed from the kidney tubule by **active transport** across the **luminal membrane** and is passively discharged to the plasma **membrane** across the **basolateral** membrane. The **tight junctions** ensure that **glucose** does not diffuse back into the **renal** tubule. **Connective tissue cells** connect, anchor, and support the structures of the body. Loose **connective tissue** consists of a loose meshwork of **cells** and fibers underlying most **epithelial** layers. Dense **connective tissue** includes the tough, rigid **tissue** that makes up tendons and ligaments. Other **connective** tissues include bone, cartilage, adipose tissue, and blood, which is considered a fluid **connective** tissue. An important function of some **connective** tissues is the formation of the extracellular **matrix** (ECM) around cells. This **matrix** consists of a mixture of proteins, polysaccharides, and, in some cases, minerals. It surrounds **cells** and includes the extracellular fluid that bathes body tissues. The **ECM** first provides a scaffold for cellular attachments and, secondly, transmits information in the form of chemical messengers to the **cells** to help regulate their activity, migration, growth, and differentiation. **Neurons** Neurons, a second specialized **cell** type, are used to initiate and conduct **electrical** signals, often over great distances. **Neurons** are a major means of controlling the activities of other cells, whether the other **cells** are neurons, muscles, or glands. The incredible complexity of connections between **neurons** underlies phenomena such as consciousness and perception. Collections of **neurons** form **nervous** tissue, such as the brain and spinal cord. Many **neurons** packaged together with **connective tissue** carry **signals** from one part of the body to another and are called nerves. **Muscle cells** are specialized to produce mechanical force that can generate movement. They can be attached to bones to produce movement of limbs, to the skin to produce facial expressions, or surround hollow **organs** or vessels to regulate the movement of materials and/or flow by changing the diameter of the chamber or vessel. **Skeletal muscle** is under voluntary control via the somatic **nervous** system, meaning that contraction and movement are consciously initiated. **Cardiac muscle** is under involuntary control via the autonomic **nervous** system and is only found in the heart. **Smooth muscle** surrounds many tubes of the body and is also under involuntary control, via the autonomic **nervous** system. Contraction and relaxation of **smooth muscle** promote or restrict the movement of materials through the body's tubes. **Organs** are composed of two or more of the four basic **tissue** types arranged in a pattern conducive to the function of the organ. Many **organs** contain smaller functional units, where each unit performs the function of the organ. An example would be the kidney, where the functional unit is a nephron, each nephron contributing a portion of the kidney's overall function (i.e., urine production). Organ **systems** are collections of **organs** that all contribute to a common function. In the **renal** system, the kidney, ureter, bladder, and urethra constitute the **renal** system, all necessary for the formation and excretion of urine. The body, therefore, consists of a collection of differentiated **cells** that combine structurally and functionally to carry out the processes necessary for the survival of the entire organism. Key to the survival of all body **cells** is the internal environment of the body. This fluid, which surrounds **cells** and exists in the blood, is the environment that most physiological **homeostatic** mechanisms are designed to modulate. The consistency of this pool is essential for the survival of the cells. A diagram of a cell structure Description automatically generated **[Compositional differences between fluid compartments of the body]** - Body fluid compartments in the human body water constitutes a high proportion of body weight. The total amount of fluid or water within the body is called the **total body water**. Normally, this accounts for **50 to 70% of body weight**. In general, total body water correlates inversely with **body fat**; hence, more body fat would translate to a lower percentage of total body water. Total body water is distributed between two major fluid compartments within the body: the **intracellular fluid** and the **extracellular fluid**. The intracellular fluid is contained within the cells and makes up **2/3 of the total body water**, and the extracellular fluid is outside of the cells and makes up the remaining **1/3**. - The composition of the extracellular fluid is very different from the composition of the intracellular fluid. Maintaining these differences in **fluid composition** across the **cell membrane** is an important way in which cells regulate their own activity. The extracellular fluid can be further subdivided into the **interstitial fluid** and the **plasma**. The interstitial fluid is the fluid that actually bathes the cells and is the larger of the two subcomponents. The plasma is the fluid circulating in the **blood vessels** and is the smaller of the two subcomponents. - The plasma and the interstitial fluid are separated by a **capillary wall**. The movement of fluid across this interface is essentially an **ultrafiltration** of plasma. The nature of this interface, the size of the gaps between **capillary cells**, and the negatively charged **glycoproteins** of the **basement membrane** mean that the capillary wall is virtually impermeable to **plasma proteins**, producing an interstitial fluid that is almost protein-free. - **Compartmentalization** is an important feature in **physiology** and is achieved by **barriers** between compartments. These barriers can be thought of as **free energy barriers** that maintain gradients of **ions**, **gases**, and **organic molecules** necessary to provide the energy to accomplish physiological work. Therefore, the properties of these barriers as they relate to the movement of particular substances are the fundamental characteristics responsible for the differences in composition observed between the compartments. - **Exchange** and **communication** are key concepts for understanding **physiologic homeostasis**. This is the fundamental property driving most physiology mechanisms. - For understanding **physiologic homeostasis**, this is the fundamental property driving most physiologic mechanisms. **\ ** - It would take millennia for scientists to determine what was being balanced and how that balance was achieved. Most cells were recognized as being in contact with the extracellular fluid and that this extracellular fluid was in flux as it exchanged materials with individual cells. It was also determined that common **physiologic factors** such as blood pressure or body temperature and bloodborne factors such as oxygen, glucose, or sodium are maintained within a predictable range despite changes in the external environment. This represented the concept that a constant internal environment was a prerequisite to good health. - **Homeostasis** is defined as a state of reasonably stable balance among **physiologic variables**. Observation suggests, however, that no physiologic variable remains constant for very long. Rather, one observes dramatic swings in variables around some average value defined as the set point. - So you see here the set point and the variations in blood glucose levels after meals. This occurs because homeostasis is not static but rather is a dynamic process. An example would be fluctuations in blood glucose levels during the typical day. Fluctuations observed for blood glucose often exhibit a rather large variation in the short term in comparison to long-term changes. This concept then describes homeostasis as a state of dynamic constancy. Thus, blood glucose may change in the short term, i.e., after a meal, but it is stable and predictable when averaged over the long term. When homeostasis is maintained, we refer to this as Physiology, and when homeostasis is not maintained, we have pathophysiology. - General characteristics of homeostatic control systems: The activities of cells, tissues, and organs must be regulated and integrated with each other so that any change in the composition of the extracellular fluid initiates a reaction to the change. The compensatory mechanisms mediating such responses are called homeostatic control mechanisms. - When considering a homeostatic control system for body temperature, we must first understand that the system is in a steady state. This is defined as a system in which a particular variable, in this case, temperature, is not changing, but a system where a constant input of heat or loss of heat is required to maintain the constant temperature. - **Steady state** is similar to equilibrium in that the variable is constant but different because energy is required to maintain steady state, whereas equilibrium is static. No energy is required to maintain a constant condition. The steady state temperature is the set point of the thermal regulatory system. This example illustrates a critical generalization about homeostasis. The stability of the internal environmental variable is achieved by the balancing of inputs and outputs. - **Feedback systems**: The thermoregulatory example is an example of a negative feedback system. A negative feedback system detects a change in a particular variable. The system reacts by adjusting the variable back toward the set point. If the internal variable increases relative to the set point, the system will respond with processes that reduce the variable back toward the set point. Negative feedback systems are very common and represent stabilizing actions. - One of the most common examples of negative feedback is allosteric regulation of metabolic pathways via end-product inhibition. The end product of a metabolic pathway will allosterically regulate an enzyme mediating one of the first reactions in that pathway. Therefore, excess end product will slow the pathway responsible for its production. So the active product then will negatively impact the ability of this enzyme to catalyze one of the initial reactions within the biochemical pathway. - **Positive feedback systems** tend to accelerate a process, moving the variable further from the set point. **Positive feedback systems** tend to be destabilizing. **Positive feedback systems** produce a rapid and powerful effect. An example would be parturition, where the stretching of the cervix by the fetus\'s head will become large enough to elicit a strong reflexive increase in the contractility of the uterine body. This pushes the baby forward, which stretches the cervix more, and the cycle continues until the baby is expelled. - Resetting of set points: Physiologic set points can be altered by changing external conditions or they can be reset by a change in internal physiology, such as might occur with the generation of a fever. Fever is an increase in the body\'s temperature set point in response to an infection. Many pathogens are at a metabolic disadvantage as temperature rises. The resetting of the body\'s thermostat is an adaptive mechanism to counter pathogen proliferation. - **Set points** for some variables change in a rhythmic pattern within the body. For example, temperature is higher in the day compared to the nighttime hours. Regulatory mechanisms can sometimes be in competition with one another, and some variables may have multiple regulatory mechanisms. **Active product** controls the sequence of chemical reactions by inhibiting the sequence\'s rate-limiting enzyme, Enzyme A. - In some variables, there may be multiple regulatory mechanisms. Feedforward regulation, another type of regulatory process often used in conjunction with feedback systems, anticipates changes in regulated variables, such as internal body temperature and energy availability. This process improves the efficiency of the body\'s homeostatic responses and minimizes fluctuations in the levels of the variables being regulated. - Examples are:\ 1. The detection of colder external temperatures by skin sensors provides input to higher brain centers to increase metabolic production of heat before any change in body temperature has occurred.\ 2. The cephalic phase of digestion, where the smell of food can stimulate the production of saliva, cause the churning of the stomach, as well as acid production, all in anticipation of the arrival of food. - Learning can also contribute to this feedforward phenomenon. We learn the consequences of particular behaviors, and the body, over time, will anticipate the perturbations to homeostasis by initiating actions before the activity begins. A familiar example is the increase in heart rate experienced by athletes before a game or an event is about to begin. - Homeostatic control systems include reflexes, which are stimulus-response sequences that respond to changes in a homeostatic variable, often without conscious input from the individual. These types of reflexes are termed **involuntary**, premeditated or built-in responses. Examples include withdrawing a hand from a hot object or blinking as an object approaches the eyes. While many reflexes appear stereotypical and automatic, they are often the result of learning and practice. Reflexes that involve complex actions are referred to as **learned or acquired reflexes**. A common example is driving a car, where most drivers can perform the intricate actions required to operate a vehicle---sometimes while engaging in other activities, such as talking on the phone. These driving actions, particularly with a manual transmission, become reflexive through practice. - The pathway mediating a reflex action is called a **reflex arc**. Afferent and efferent pathways in temperature homeostasis.  **Stimulus**: A change in the environment initiates the reflex.  **Receptor**: Detects and transduces the stimulus into a signal.  **Afferent Pathway**: Carries the signal from the receptor to the integrating center.  **Integrating Center**: Compares the input signal to a set point. It processes and generates an output signal to initiate the response.  **Efferent Pathway**: Transmits the output signal from the integrating center to the effector. This pathway can involve neural or hormonal signals.  **Effector**: Executes the appropriate response, such as a muscle contracting or a gland releasing a hormone.  **Response**: The action performed by the effector, which typically restores homeostasis or mitigates the stimulus A diagram of a path Description automatically generated - Importantly, *reflexes do not exclusively involve nervous pathways.* Hormones can serve as efferent/afferent pathways instead of nerves and may work in conjunction with neural pathways. For example, if an endocrine gland functions as the integrating center, a hormone may be released as the efferent signal. Regardless, afferent and efferent pathways must always differ from each other. While both pathways can involve neurons or hormones, they operate as one-way communication systems.Additionally, **local homeostatic responses** can occur, involving similar principles but on a localized scale rather than system-wide. \* **Local Homeostatic Responses**\ These responses are initiated by a change in the internal or external environment, including an alteration in cell activity, with the net effect of countering the stimulus. Like a reflex, a local response is the result of a sequence of events triggered by a stimulus. Unlike a reflex, however, a local response generates the entire sequence of events within the vicinity of the stimulus. For example, active hyperemia is a reaction of the vascular smooth muscle to changes in factors associated with increased cellular metabolism found in the extracellular fluid. Increases in factors such as carbon dioxide, hydrogen ion concentration, adenosine, potassium, eicosanoids, osmolarity, bradykinins, and nitric oxide all induce vasodilation of the smooth muscle. This, in turn, increases the delivery of gases and nutrients to the more rapidly metabolizing cells. This mechanism provides individual areas of the body with the means of local self-regulation. \* **The Role of Intracellular Chemical Messengers in Homeostasis**\ Essential to reflexes and local homeostatic responses is the ability of cells to communicate with one another. This allows cells in one part of the body to be aware of the activities of cells in another part of the body. In the majority of cases, intracellular communication is performed by chemical messengers. Groups of chemical messengers include hormones, neurotransmitters, paracrine, and autocrine substances. - **Hormones** function as chemical messengers by allowing hormone-secreting tissue or the endocrine gland to communicate via bloodborne hormones with specific cells containing receptor proteins, i.e., the target cells, which bind the hormone and generate a cellular response. Long-distance communication via hormones plays a key role in essentially all physiological processes, including growth, reproduction, metabolism, mineral balance, and blood pressure. - **Neurotransmitters** are chemical messengers that are released from the endings of neurons into or onto other neurons, muscle cells, or gland cells. A neurotransmitter diffuses through the extracellular fluid separating the neuron from its target cell. It is very hard to clearly distinguish between chemical and neural messengers when synapses rely upon neurotransmitters to continue the electrical signal from one neuron to the next. Neurons provide neurotransmitters for local information transfer, neural hormones that act upon remote effector cells (which include the adrenal medulla and hypothalamus), and hormones that are usually transported in the cardiovascular system. - **Paracrine Substances** are chemical messengers involved in local responses. They are synthesized and excreted into the extracellular fluid, which then diffuses to neighboring cells. They are inactivated rapidly by local enzymes found within the extracellular matrix, which prevents their entry into the bloodstream. - **Autocrine Substances** are released by a cell, but the chemical acts essentially upon the same cell. The cell contains a receptor protein for this autocrine substance. - A given signal can fit into all 3 categories: **Hormone-secreting(hormone)/Nerve cell(Neurotransmitter)/Local cell(Paracrine and Autocrine)**  - **Adaptation and Acclimatization: Processes Related to Homeostasis**\ Adaptation denotes a characteristic that favors survival in specific environments. Homeostatic control systems are inherited biological adaptations. A body\'s response to a particular environmental stress is not fixed; prolonged exposure, for example, can improve the function of an already existing homeostatic system. This altered response to prolonged exposure is termed **acclimatization**. Acclimatization, therefore, is an adjustment in the homeostatic system that better adapts the person to current conditions. Acclimatization is dynamic and reversible, such that processes will continually change as environmental conditions change. An example of acclimatization would be the ascent to altitude and the physiological changes associated with gas exchange resulting from the reduction in the partial pressure of oxygen in the atmosphere. - **Biological Rhythms and Homeostasis**\ A striking characteristic of many body functions is that they are rhythmic. They exhibit cyclic changes. The most common type of cyclic change in the body is **circadian rhythms**, which have a periodicity of approximately 24 hours. Such variation is a means of anticipating and therefore limiting fluctuations in key homeostatic variables. For example, body temperature increases just prior to the wakeful period compared to the period of sleep. An increase in body temperature enhances the efficiency of metabolic activity necessary to support wakeful actions. These rhythms are not environmentally driven; rather, they are set internally, with environmental cues acting to establish the actual hours of the basic rhythm. This process is termed **entrainment**. The neural basis of these rhythms is located in a collection of neurons found in the hypothalamus. The **suprachiasmatic nucleus** serves as the pacemaker or time clock for circadian rhythms. What do biological rhythms have to do with homeostasis? They add an anticipatory component to homeostatic control systems and, in effect, are a **feedforward system** operating without detectors. The negative feedback homeostatic responses are corrective responses; they are initiated after the steady state of the individual has been perturbed. Biological rhythms enable homeostatic mechanisms to be utilized immediately and automatically by activating them at times when a challenge is likely to occur, but before it actually does. *A full analysis of the hormone cortisol requires not only knowledge of the signals that cause its synthesis and secretion but also consideration of biological rhythms.*\ A graph showing time and light Description automatically generated - **Balance of Chemical Substances in the Body\ **\ Many homeostatic systems regulate the addition and removal of chemical substances from the body. We can generalize this scheme as follows: - The pathways to the left of the figure denote sources of net gain to the body. Materials can enter through the gastrointestinal (GI) tract or the lungs. Alternatively, some substances entering the body are synthesized within the body via, for example, gluconeogenesis. - Pathways to the right of the figure denote causes of net loss from the body. Substances may be removed by excretion or may be enzymatically altered and hence removed metabolically. - The central portion of the figure illustrates the distribution of substances within the body. The **pool** is analogous to the concentration of substances found within the extracellular fluid. These are the levels of substances encountered by cells of the body. Substances can be stored (e.g., in adipose tissue), temporarily incorporated into other molecules, or attached to transport proteins or intracellular proteins. The **set point** describes the target concentration for the pool. Homeostatic mechanisms are designed to regulate fluctuations of the pool by adjusting movements to and from storage and by altering inputs and outputs. For homeostasis to be achieved, inputs must equal outputs. Adjustments within limit fluctuations are thus made by homeostatic processes to regulate the pool depending on the direction and magnitude of the change. Three states of balance are possible: 1. **Negative Balance:** Loss exceeds gain for a substance. 2. **Positive Balance:** Gain exceeds loss for a substance. 3. **Stable Balance:** Gain equals loss for a substance. Physiological research has been directed at describing key pathways for regulating each substance. However, there are limits to the magnitude of inputs and outputs. Disruption of any one pathway can lead to imbalance. Essential nutrients must always have an input. Sodium, for example, is regulated to maintain a stable pool size within a range of ingestion rates. If ingestion rates change abruptly, several days may be required to regain homeostasis. Within the acceptable range of nutrient input is an **optimal level**. This level may not be the same for good health or to avoid disease. Different levels of a nutrient may be optimal for different aspects of health. For example, increased protein intake can promote larger body size but may also lead to an increased risk of cancer. The National Academy of Sciences' **Recommended Daily Allowances (RDAs)** provide guidelines for minimal intake of nutrients to avoid disease symptoms. However, these levels of intake may not necessarily be optimal for good health. **Summary of Homeostasis** 1. Homeostasis is essential for health and survival. 2. The functions of organ systems are coordinated with each other. 3. Most physiological functions are controlled by multiple regulatory systems, often working in opposition to one another. 4. Information flow between cells, tissues, and organs is an essential feature of homeostasis and allows for the integration of physiological processes. 5. Controlled exchange of materials occurs between compartments and across cellular membranes. 6. Physiological processes are dictated by the laws of chemistry and physics. 7. Structure is a determinant of, and has co-evolved with, function.