Big Idea #4: Interactions

Thermoregulation

KEY POINTS The skin's immense blood supply helps regulate temperature: dilated vessels allow for heat loss, while

constricted vessels retain heat. The skin regulates body temperature with its blood supply. The skin assists in homeostasis. Humidity affects thermoregulation by limiting sweat evaporation and thus heat loss. The integumentary system also functions in thermoregulation, the ability of an organism to keep its body

temperature within certain boundaries, even when the surrounding temperature is very different. This process is one aspect of homeostasis: a dynamic state of stability between an animal's internal and external environment.

SkinThe skin assists in homeostasis (keeping different aspects of the body constant, e.g. temperature). It does this by reacting differently to hot and cold conditions so that the inner body temperature remains more or less constant. Vasodilation and sweating are the primary modes by which humans attempt to lose excess body heat.

In hot conditions, endocrine sweat glands under the skin secrete sweat (a fluid containing mostly water with some dissolved ions) which travels up the sweat duct, through the sweat pore and onto the surface of the skin. This causes heat loss via evaporative cooling; however, a lot of essential water is lost.

In cold conditions sweat stops being produced. The arrector pili muscles contract (piloerection), lifting the hair follicles upright. This makes the hairs stand on end which acts as an insulating layer, trapping heat. This is also how "goose bumps" are caused, since humans don't have very much hair and the contracted muscles can easily be seen.

ARTERIOLES Arteriole vasodilation is the process of relaxation of smooth muscle in arteriole walls, allowing increased blood flow through the artery. This redirects blood into the superficial capillaries in the skin increasing heat loss by convection and conduction.

Arterioles carrying blood to superficial capillaries under the surface of the skin can shrink (constrict), thereby rerouting blood away from the skin and towards the warmer core of the body. This prevents blood from losing heat to the surroundings and also prevents the core temperature dropping further. This process is called vasoconstriction.

It is impossible to prevent all heat loss from the blood, only to reduce it. In extremely cold conditions, excessive vasoconstriction leads to numbness and pale skin. Frostbite only occurs when water within the cells begins to freeze; this destroys the cell and causes damage.

MUSCLES Muscles can also receive messages from the thermoregulatory center of the brain (the hypothalamus) to cause shivering. This increases heat production as respiration is an exothermic reaction in muscle cells. Shivering is more effective than exercise at producing heat because the animal remains still; less heat is lost to the environment via convection.

There are two types of shivering: low intensity and high intensity. During low intensity shivering, animals shiver constantly at a low level for months during cold conditions. During high intensity shivering, animals shiver violently for a relatively short time. Both processes consume energy although high intensity shivering uses glucose as a fuel source and low intensity tends to use fats.

The Musculoskeletal System

KEY POINTS The musculoskeletal system's primary functions include supporting the body, allowing motion, and protecting

vital organs. The musculoskeletal system is made up of the body's bones (the skeleton), muscles, cartilage, tendons,

ligaments, joints, and other connective tissue that supports and binds tissues and organs together. The skeleton serves as the main storage system for calcium* and phosphorus. The skeleton also contains critical components of the hematopoietic (blood production) system and fat

storage. These functions occur in red marrow and yellow marrow, respectively. To allow motion, different bones are connected by articulating joints. Cartilage prevents the bone ends from

rubbing directly on to each other while the muscles contract, or undergo shortening, to move the bones associated with the joint.

The musculoskeletal system (also known as the locomotor system) is an organ system that gives animals (including humans) the ability to move, using the muscular and skeletal systems. It provides form, support, stability, and movement to the body.

The musculoskeletal system is made up of the body's bones (the skeleton), muscles, cartilage, tendons, ligaments, joints, and other connective tissue that supports and binds tissues and organs together. Its primary functions include supporting the body, allowing motion, and protecting vital organs.

*The skeletal portion of the system serves as the main storage system for calcium and phosphorus.

The importance of this storage "device" helps to regulate mineral balance in the bloodstream. When the fluctuation of minerals is high, these minerals are stored in bone; when it is low, minerals are withdrawn from the bone.

KEY POINTS Calcium homeostasis regulates calcium

flow to and from the bones. Inadequate calcium levels can result in

osteoporosis. Calcium release from bone is regulated by

parathyroid hormone. Vitamin D is converted to calcidoil in the

liver, which is then converted to calcitriol, the biologically active form of vitamin D, in the kidneys.

Calcitriol regulates the levels of calcium and phosphorus in the blood and helps maintain a healthy skeletal system.

Bone resorption by osteoclasts releases calcium into the bloodstream which helps regulate calcium homeostasis.

Immune Response

KEY POINTS Helper T cells become activated to divide rapidly and secrete small proteins called cytokines that regulate or

assist in the active immune response. Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells, and are also implicated in

transplant rejection. Memory T cells persist long-term after an infection has resolved. They quickly expand to large numbers of

effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with "memory" against past infections.

Regulatory T cells are crucial for the maintenance of immunological tolerance. Natural killer T cells bridge the adaptive immune system with the innate immune system by producing

cytokines.

Introduction to T Cells T helper cells (TH cells) assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages. These cells are also known as CD4+ T cells because they express the CD4 protein on their surface. Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules, which are expressed on the surface of antigen presenting cells (APCs). Once activated, they divide rapidly and secrete small proteins called cytokines which regulate or assist in the active immune response. These cells can differentiate into one of several subtypes, including TH1, TH2, TH3, TH17, or TFH, which secrete different cytokines to facilitate a different type of immune response. Signaling from the APC directs T cells into particular subtypes.

Hematopoietic (blood production) SystemThe skeleton also contains critical components of the hematopoietic (blood production) system. Located in long bones are two distinctions of bone marrow: yellow and red. The yellow marrow has fatty connective tissue and is found in the marrow cavity. In times of starvation, the body uses the fat in yellow marrow for energy. The red marrow of some bones is an important site for hematopoiesis or blood cell production: approximately 2.6 million red blood cells per second, in order to replace existing cells that have been destroyed by the liver. Here, all erythrocytes, platelets, and most leukocytes form in adults, from where they migrate to the blood to do their special tasks.

The bones provide stability to the body analogous to a reinforcement bar in concrete construction. Muscles keep bones in place and also play a role in movement of the bones. To allow motion, different bones are connected by articulating joints and cartilage prevents the bone ends from rubbing directly onto each other.Muscles contract (shorten) to move the bone attached at the joint. Skeletal muscles are attached to bones and arranged in opposing groups around joints. Muscles are innervated; the nerves conduct electrical currents from the central nervous system, causing the muscles to contract.

Cytotoxic T cells Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells since they express the CD8 glycoprotein at their surface. They recognize their targets by binding to antigen associated with MHC class I, which is present on the surface of nearly every cell of the body. Through IL-10 - adenosine and other molecules secreted by regulatory T cells - the CD8+ cells can be inactivated to an anergic state, which prevent autoimmune diseases such as experimental autoimmune encephalomyelitis.

Memory T Cells Memory T cells are a subset of antigen-specific T cells that persist for a long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen, thus providing the immune system with "memory" against past infections. Memory T cells comprise two subtypes: central memory T cells (TCM cells) and effector memory T cells (TEM cells). Memory cells may be either CD4+ or CD8+. Memory T cells typically express the cell surface protein CD45RO.

Regulatory T Cells Regulatory T cells (Treg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cell-mediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4+ Treg cells have been described — naturally occurring Treg cells and adaptive Treg cells. Naturally occurring Treg cells (also known as CD4+CD25+FoxP3+ Treg cells) arise in the thymus and have been linked to interactions between developing T cells with both myeloid (CD11c+) and plasmacytoid (CD123+) dendritic cells that have been activated with TSLP. Naturally occurring Treg cells can be distinguished from other T cells by the presence of an intracellular molecule called FoxP3. Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal autoimmune disease IPEX. Adaptive Treg cells (also known as Tr1 cells or Th3 cells) may originate during a normal immune response.

Natural Killer T Cells Natural killer T cells (NKT cells – not to be confused with natural killer cells) bridge the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigens presented by major histocompatibility complex (MHC) molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d. Once activated, these cells can perform functions ascribed to both Th and Tc cells (i.e., cytokine production and release of cytolytic/cell killing molecules). They are also able to recognize and eliminate some tumor cells and cells infected with herpes viruses.

The Lymphatic System

The lymphatic system plays a prominent role in immune function, fatty acid absorption, and removal of interstitial fluid from tissues.

KEY POINTS The lymphatic system is a linear network of lymphatic vessels and secondary lymphoid organs. It is responsible for the removal of interstitial fluid from tissues. It absorbs and transports fatty acids and fats as chyle from the digestive system. It transports white blood cells to and from the lymph nodes into the bones.

The lymphatic system has multiple interrelated functions: (1) It is responsible for the removal of interstitial fluid from tissues, (2) it transports white blood cells to and from the lymph nodes into the bones, (3) it absorbs and transports fatty acids and fats as chyle from the digestive system, and (4) the lymph transports antigen-presenting cells (APCs), such as dendritic cells, to the lymph nodes where an immune response is stimulated.

REMOVAL OF FLUID AND CIRCULATION OF BLOOD CELLS The lymphatic system is a linear network of lymphatic vessels and secondary lymphoid organs. Macroscopically, the blood vascular system is literally a circular system in which the fluid (blood) leaves the heart; runs through the arteries, arterioles, capillary plexus, venules, and veins; and returns to the heart. In contrast, the lymphatic system is a blunt-ended linear system, in which tissue fluids, cells, and large extracellular molecules, collectively called lymph, are drained into the initial lymphatic capillary vessels that begin at the interstitial spaces of tissues and organs; are transported to thicker collecting lymphatics, which are embedded with multiple lymph nodes; and are eventually returned to the blood circulation through the thoracic or lymphatic ducts that join to the subclavian veins.

FATTY ACID TRANSPORTLymphatic vessels such as lacteals in the intestines absorb and transport large molecules, fats, and lipids in the digestive system mainly in the form of lipoprotein such as chylomicrons—large lipoprotein particles that are created by the enterocytes of the intestine and consist of triglycerides, phospholipids, cholesterol, and proteins. Notably, lymph fluid and chylomicrons can stimulate adipocyte differentiation.

IMMUNE CELL TRAFFICKING In addition to the tissue fluid homeostasis, the lymphatic system serves as a conduit for trafficking of lymphocytes and antigen-presenting cells to regional lymph nodes, where the immune system encounters pathogens, microbes, and other immune elicitors. Lymph-node lymphatic vessels, which uptake various antigens from peripheral tissues, are positively regulated by chemokines/cytokines secreted by B cells, macrophages, and dendritic cells during inflammation.

The Lymphatic System

The lymphatic system plays a prominent role in immune function, fatty acid absorption, and removal of interstitial fluid from tissues.

KEY POINTS The lymphatic system is a linear network of lymphatic vessels and secondary lymphoid organs. It is responsible for the removal of interstitial fluid from tissues. It absorbs and transports fatty acids and fats as chyle from the digestive system. It transports white blood cells to and from the lymph nodes into the bones.

The lymphatic system has multiple interrelated functions: (1) It is responsible for the removal of interstitial fluid from tissues, (2) it transports white blood cells to and from the lymph nodes into the bones, (3) it absorbs and transports fatty acids and fats as chyle from the digestive system, and (4) the lymph transports antigen-presenting cells (APCs), such as dendritic cells, to the lymph nodes where an immune response is stimulated.

REMOVAL OF FLUID AND CIRCULATION OF BLOOD CELLS The lymphatic system is a linear network of lymphatic vessels and secondary lymphoid organs. Macroscopically, the blood vascular system is literally a circular system in which the fluid (blood) leaves the heart; runs through the arteries, arterioles, capillary plexus, venules, and veins; and returns to the heart. In contrast, the lymphatic system is a blunt-ended linear system, in which tissue fluids, cells, and large extracellular molecules, collectively called lymph, are drained into the initial lymphatic capillary vessels that begin at the interstitial spaces of tissues and organs; are transported to thicker collecting lymphatics, which are embedded with multiple lymph nodes; and are eventually returned to the blood circulation through the thoracic or lymphatic ducts that join to the subclavian veins.

FATTY ACID TRANSPORTLymphatic vessels such as lacteals in the intestines absorb and transport large molecules, fats, and lipids in the digestive system mainly in the form of lipoprotein such as chylomicrons—large lipoprotein particles that are created by the enterocytes of the intestine and consist of triglycerides, phospholipids, cholesterol, and proteins. Notably, lymph fluid and chylomicrons can stimulate adipocyte differentiation.

IMMUNE CELL TRAFFICKING In addition to the tissue fluid homeostasis, the lymphatic system serves as a conduit for trafficking of lymphocytes and antigen-presenting cells to regional lymph nodes, where the immune system encounters pathogens, microbes, and other immune elicitors. Lymph-node lymphatic vessels, which uptake various antigens from peripheral tissues, are positively regulated by chemokines/cytokines secreted by B cells, macrophages, and dendritic cells during inflammation.

Osmoregulation- Fluid INTAKE

KEY POINTS A constant supply is needed to replenish the

fluids lost through normal physiological activities, such as respiration, sweating, and urination.

The macula densa region of the kidney's juxtaglomerular apparatus is another modulator of blood osmolality. The macula densa responds to changes in osmotic pressure through changes in the rate of chloride anion flow through the nephron.

An insufficiency of water results in an increased osmolarity in the extracellular fluid.

Increased osmolarity is sensed by osmoreceptors.

Water generated from the biochemical metabolism of nutrients provides a significant proportion of the daily water requirements for some arthropods and desert animals; but it provides only a small fraction of a human's necessary intake.

Body water homeostasis is regulated mainly through ingested fluids, which, in turn, depends on thirst. An insufficiency of water results in an increased osmolarity in the extracellular fluid. This is sensed by osmoreceptors which trigger the sensation of thirst. Thirst can to some degree be voluntarily resisted, as during fluid restriction.

The Kidney In the physiology of the kidney, free water clearance (CH2O) is the volume of blood plasma that is cleared of solute-free water per unit time. An example of its use is in the determination of an individual's state of hydration. Conceptually, free water clearance should be thought of as relative to the production of isoosmotic urine, which would be equal to the osmolarity of the plasma. If an individual is producing urine more dilute than the plasma, there is a positive value for free water clearance; this means pure water is lost in the urine in addition to a theoretical isoosmotic filtrate. If the urine is more concentrated than the plasma, then free water is being extracted from the serum, giving a negative value for free water clearance. A negative value is typical for free water clearance, as the kidney usually produces concentrated urine, except in the cases of volume overload by the individual.

Osmoreceptors An osmoreceptor is a sensory receptor, primarily found in the hypothalamus of most homeothermic organisms, that detects changes in osmotic pressure. Osmoreceptors can be found in several structures, including the organum vasculosum of the lamina terminalis (OVLT) and the subfornical organ (SFO). They contribute to fluid balance in the body.Osmoreceptors, as the name suggests, sense change in osmotic pressure. When the osmotic pressure of blood changes (i.e. it is more or less dilute), water diffusion into and out of the osmoreceptor cells changes. That is, they expand when the blood plasma is more dilute and contract with higher concentration. This causes an afferent neural signal to be sent to the hypothalamus, which increases or decreases vasopressin (ADH) secretion from the posterior pituitary to return blood concentration to normal.

Several complex pathways trigger aldosterone release from the adrenal cortex, direct vasoconstriction, and thirst behaviors originating in the hypothalamus.

Osmoregulation- Fluid OUTPUT

KEY POINTS The majority of fluid output occurs via the urine.

Some fluid is lost through perspiration (part of the body's temperature control mechanism) and as water vapor in expired air.

The body's homeostatic control mechanisms ensure that a balance between fluid gain and fluid loss is maintained. The hormones ADH (antidiuretic hormone, also known as vasopressin) and aldosterone play a major role in this.

If the body is becoming fluid-deficient, this will be sensed by osmoreceptors, which results in increased secretion of ADH, causing fluid to be retained by the kidneys and urine output to be reduced.

The hormones ADH (Anti-diuretic Hormone, also known as vasopressin) and aldosterone play a major role in this.

If the body is becoming fluid-deficient, this will be sensed by osmoreceptors.

Fluid can leave the body in several ways: Urination excretion (feces) perspiration (sweating)

The majority of fluid output occurs via the urine, at approximately 1500 ml/day (approx 1.59 qt/day) in a normal adult at resting state. Some fluid is lost through perspiration (part of the body's temperature control mechanism) and as water vapor in expired air.

The body's homeostatic control mechanisms, which maintain a constant internal environment, ensure that a balance between fluid gain and fluid loss is maintained. The hormones ADH (anti-diuretic hormone, also known as vasopressin) and aldosterone play a major role in this. If the body is becoming fluid-deficient, there will be an increase in the secretion of these hormones, causing fluid to be retained by the kidneys and urine output to be reduced. Conversely, if fluid levels are excessive, secretion of these hormones is suppressed, resulting in less retention of fluid by the kidneys and a subsequent increase in the volume of urine produced.

If the body is becoming fluid-deficient, this will be sensed by osmoreceptors , thus, there will be an increase in the secretion of antidiuretic hormone, causing fluid to be retained by the kidneys and urine output to be reduced.

The Urinary System

KEY POINTS The urinary system organs include the kidneys, ureter, bladder, and urethra. The kidneys have six important roles: regulation of plasma ionic composition, osmolality, plasma volume, blood

pressure, hydrogen ion concentration, removal of metabolic waste products and secretion of hormones. The primary function of the kidneys is to maintain a stable internal environment (homeostasis) for optimal cell

and tissue metabolism. They do this by separating urea, mineral salts, toxins, and other waste products from the blood.

Kidneys are the most complex and critical part of the urinary system. The primary function of the kidneys is to maintain a stable internal environment (homeostasis) for optimal cell and tissue metabolism. They do this by separating urea, mineral salts, toxins, and other waste products from the blood. Six important roles of the kidneys are:

1. regulation of plasma ionic composition such as sodium, potassium, calcium, magnesium, chloride, bicarbonate, and phosphate ions by the amount that the kidney excretes.

2. regulation of plasma osmolarity by regulating how many ions and how much water a person excretes.

3. regulation of plasma volume and blood pressure by controlling how much water a person excretes. The plasma volume has a direct effect on the total blood volume, which has a direct effect on your blood pressure.

4. regulation of plasma hydrogen ion concentration (pH) in concert with the lungs. The kidneys control the amount of bicarbonate excreted or held onto and maintain blood pH by excreting hydrogen ions and reabsorbing bicarbonate ions as needed.

5. removal of metabolic waste products and foreign substances from the plasma.

6. secretion of hormones such as renin which in turn leads to the secretion of aldosterone which helps kidneys to reabsorb the sodium (Na+) ions. The kidneys also secrete erythropoietin which stimulates red blood cell production.