Animal Form, Function, Homeostasis, Reproduction and Development

An animal is a society of cells that has to keep one small pond of fluid, the extracellular fluid, stable while the outside world swings from freezing to scorching, from feast to famine and from calm to danger. Every organ system in this chapter, from the gut and the heart to the kidney, the immune system and the brain, exists to defend that internal pond or to pass the whole arrangement on to the next generation. Once you see each system as a solution to a physical problem (surface area, diffusion distance, signal speed, water loss), animal physiology stops being a list of organs and becomes a set of ideas you can reason with.

Section 1Tissues, homeostasis and thermoregulation

Levels of organization and the four tissue types

Animal bodies are built in a hierarchy: cells form tissues, tissues combine into organs, and organs that work toward a shared task form an organ system. A tissue is a group of cells with a common structure and function, together with the material they secrete around themselves. Every animal organ, from the stomach of a squid to the heart of a horse, is assembled from just four tissue types.

• Epithelial tissue covers outside surfaces and lines internal cavities and tubes. Its cells are packed tightly, joined by junctions, and sit on a basement membrane (basal lamina). One surface faces a lumen or the outside (the apical surface) and the other faces the basement membrane (the basal surface), so epithelia are polarized.
• Connective tissue has relatively few cells scattered in an extracellular matrix of protein fibers (collagen, elastic and reticular fibers) and ground substance. Loose connective tissue, fibrous connective tissue (tendons and ligaments), adipose tissue, cartilage, bone and blood are all connective tissues.
• Muscle tissue contracts. Skeletal muscle is striated and voluntary, cardiac muscle is striated, branched and joined by intercalated disks, and smooth muscle lacks striations and lines the gut, blood vessels and bladder.
• Nervous tissue receives, processes and transmits information. Neurons carry electrical signals, and glial cells support, insulate and nourish them.

Size, shape and the exchange problem

Every cell must exchange gases, nutrients and wastes with a watery environment, and diffusion is only fast over very short distances. The time diffusion takes rises with the square of the distance, so doubling the distance makes the trip four times slower. A one celled organism or a two cell thick hydra can rely on direct contact with the surrounding water. Larger animals cannot, because as an object grows its volume (the cells that need supplies) increases with the cube of its length while its surface area (the place where exchange happens) increases only with the square. The surface area to volume ratio therefore falls as size increases.

Animals solve this problem in two ways. Some stay thin or flat, like flatworms, so every cell is near the surface. Most evolve internal exchange surfaces that are enormously folded or branched (lungs, gills, intestinal villi, kidney tubules) and a circulatory system that carries materials between those surfaces and every cell. A recurring theme of this chapter is this pairing: a huge, thin exchange surface plus a transport system that keeps the gradients steep.

Homeostasis: regulating the internal environment

The cells of complex animals live in an internal environment, the interstitial fluid, and the maintenance of a relatively constant internal state is homeostasis. Body temperature, blood glucose, blood pH (near 7.4), blood calcium, osmolarity and blood pressure are all held within narrow ranges. Homeostasis does not mean that nothing changes; it means that variables fluctuate around a set point and are pushed back when they drift.

A homeostatic control system has four parts. A stimulus is a change in the variable. A sensor (receptor) detects it. A control center (integrator), often in the brain or an endocrine gland, compares the reading with the set point. An effector (a muscle or gland) makes the response that moves the variable back.

Negative and positive feedback

In negative feedback, the response opposes the stimulus, so the variable returns toward the set point and the system stabilizes. Nearly all homeostatic control is negative feedback. When blood glucose rises after a meal, the pancreas releases insulin, cells take up glucose and glucose falls; the fall then reduces insulin release.

In positive feedback, the response amplifies the stimulus, driving the variable farther from its starting point until some outside event ends the loop. Positive feedback is used for processes that must be completed quickly rather than held steady. During childbirth, pressure of the baby's head on the cervix triggers release of oxytocin, which strengthens uterine contractions, which push the head harder against the cervix, which releases more oxytocin; delivery ends the cycle.

Thermoregulation: endotherms and ectotherms

Temperature matters because enzymes, membranes and reaction rates are all temperature sensitive.

Endotherms, mainly birds and mammals, warm their bodies with heat generated by their own metabolism. Ectotherms, including most invertebrates, fishes, amphibians and nonavian reptiles, gain most of their heat from the environment. These terms describe the heat source; the older terms warm blooded and cold blooded are misleading, because a lizard basking in desert sun can have a higher body temperature than a mammal. Endothermy costs roughly five to ten times more energy than ectothermy at rest but allows sustained activity in the cold; ectotherms can survive long periods on little food.

Four routes of heat exchange

Every organism exchanges heat with its surroundings by four physical processes. Radiation is the emission of electromagnetic (infrared) energy and works without contact, as when a lizard absorbs sunlight. Conduction is direct transfer between objects in contact, such as a body lying on cold rock; water conducts heat about 25 times better than air, which is why cold water chills you so fast. Convection is transfer by moving air or water across a surface; wind chill is convection. Evaporation removes heat as water changes to vapor, because water has a high heat of vaporization. Sweating, panting and licking fur all exploit evaporative cooling.

Adaptations for thermoregulation

Animals adjust heat exchange using several overlapping strategies.

• Insulation. Fur, feathers and fat reduce heat flow. Marine mammals rely on a thick layer of blubber, because wet fur insulates poorly. Raising fur or feathers traps more still air; goosebumps in humans are the remnant of this reflex.
• Circulatory adjustments. Vasodilation of surface vessels carries warm blood to the skin and increases heat loss; vasoconstriction reduces it. Countercurrent heat exchangers place warm arteries beside cool veins flowing in the opposite direction, so heat passes from outgoing arterial blood to returning venous blood before it reaches the extremity. Geese standing on ice, dolphin flippers and the legs of arctic foxes all use this arrangement.
• Evaporative cooling. Sweating (humans, horses), panting (dogs, birds) and spreading saliva are all evaporative.
• Behavior. Basking, seeking shade, burrowing, huddling, orienting the body toward or away from the sun and migrating are often the cheapest responses.
• Adjusting metabolic heat production. Shivering thermogenesis uses muscle contraction to generate heat. Nonshivering thermogenesis raises metabolic rate through hormones (thyroid hormone, epinephrine), and in mammals brown adipose tissue, packed with mitochondria, uses the uncoupling protein thermogenin (UCP1) to let protons leak across the inner mitochondrial membrane so that the energy of the gradient is released as heat rather than used to make ATP.

In mammals the hypothalamus acts as the thermostat. When blood or skin temperature rises it triggers vasodilation and sweating; when temperature falls it triggers vasoconstriction, shivering and nonshivering thermogenesis. A fever is not a failure of the thermostat but a deliberate resetting of the set point upward, triggered by molecules called pyrogens released during infection. That is why a person with a rising fever feels chilled and shivers: the body is below its new set point.

Section 2Nutrition, circulation and gas exchange

What animals need from food

Animals are heterotrophs: they must eat organic molecules made by other organisms. Food supplies three things. It supplies chemical energy to make ATP, organic building blocks (carbon skeletons and organic nitrogen) to build the body's own molecules, and essential nutrients that the animal cannot make for itself. The essential nutrients fall into four groups: essential amino acids (nine for adult humans, including lysine, methionine and tryptophan), essential fatty acids (linoleic and alpha linolenic acids in humans), vitamins (organic molecules needed in small amounts, many of which become coenzymes) and minerals (inorganic elements such as calcium, iron and iodine).

The four stages of food processing

Food processing happens in four stages. Ingestion is taking food in. Digestion breaks large molecules into monomers small enough to absorb, first mechanically (chewing, churning) and then chemically by enzymatic hydrolysis, in which water is added across the bonds that link monomers. Absorption is the uptake of those monomers by the cells lining the gut. Elimination is the removal of undigested material as feces.

Most animals digest food outside cells, in a compartment. Cnidarians and flatworms have a gastrovascular cavity with a single opening that serves as both mouth and anus. Most other animals have an alimentary canal, a complete tube with a mouth and an anus, which allows specialized regions to act in sequence and allows the animal to eat again before the previous meal is finished.

The mammalian digestive system

In humans, digestion begins in the oral cavity, where teeth break up food and saliva supplies salivary amylase to start starch digestion and mucus to lubricate the bolus. The bolus then passes down the esophagus, where waves of smooth muscle contraction called peristalsis move it to the stomach.

The stomach stores food and begins protein digestion. Its gastric glands secrete hydrochloric acid (from parietal cells), bringing the pH to about 2, which denatures proteins and kills many microbes, and pepsinogen (from chief cells), which acid converts to the active protease pepsin. Churning produces a soupy mixture called chyme, released in small amounts through the pyloric sphincter.

The small intestine is where most digestion and nearly all absorption occur. Its first part, the duodenum, receives bile from the liver (stored in the gallbladder) and digestive juice from the pancreas. Bile salts are not enzymes; they emulsify fats into tiny droplets that give lipase more surface to work on. Pancreatic juice contains bicarbonate, which neutralizes acid chyme, and enzymes including pancreatic amylase, trypsin and chymotrypsin, lipase and nucleases. Enzymes attached to the intestinal epithelium, such as maltase, lactase, sucrase and peptidases, finish the job. The lining is folded into villi, and each epithelial cell bears microvilli (the brush border), multiplying the absorptive surface. Sugars and amino acids enter blood capillaries in each villus and travel through the hepatic portal vein to the liver, which regulates their release to the body. Fats are reassembled into triglycerides, packaged into chylomicrons and enter a lymph vessel in the villus called a lacteal.

The large intestine (colon) reabsorbs water and houses a dense community of bacteria, the gut microbiome, which ferments fiber into short chain fatty acids and makes vitamin K and some B vitamins. The rectum stores feces until elimination.

Why circulate? Open and closed systems

Once nutrients are absorbed and oxygen is taken in, they must reach every cell. A circulatory system has three parts: a circulatory fluid, a set of vessels or spaces, and a muscular pump, the heart. It converts the slow, short range process of diffusion into fast, long range bulk flow.

In an open circulatory system, found in arthropods and most mollusks, the heart pumps fluid called hemolymph through vessels that open into sinuses surrounding the organs, so the circulatory fluid and interstitial fluid are the same. In a closed circulatory system, found in annelids, cephalopods (squid and octopus) and all vertebrates, blood stays inside vessels and is separate from interstitial fluid. Closed systems maintain higher pressure, deliver oxygen faster and allow blood flow to be directed to particular organs. Open systems use less energy and, in insects, work well because oxygen reaches tissues directly through air tubes called tracheae rather than through the blood.

Blood vessels and blood

Arteries carry blood away from the heart; they have thick, elastic and muscular walls that withstand high pressure. Arteries branch into arterioles and then into capillaries, whose walls are a single layer of endothelial cells. Capillary beds are where exchange with tissues happens. Capillaries merge into venules and veins, which carry blood back to the heart. Veins have thinner walls, low pressure and valves that prevent backflow; skeletal muscle contraction squeezes veins and helps return blood. The direction of flow, not the oxygen content, defines artery versus vein: the pulmonary artery carries oxygen poor blood, and the pulmonary veins carry oxygen rich blood.

Human blood is about 55 percent plasma (water, ions, plasma proteins such as albumin, fibrinogen and antibodies, nutrients and wastes) and 45 percent cellular elements. Red blood cells (erythrocytes) carry oxygen bound to hemoglobin; mammalian red cells lack nuclei and mitochondria, leaving more room for hemoglobin. White blood cells (leukocytes) defend the body. Platelets are cell fragments that start clotting.

The vertebrate heart and double circulation

Fishes have a two chambered heart (one atrium, one ventricle) and single circulation: blood passes from heart to gills to body and back to the heart. Amphibians, reptiles, birds and mammals have double circulation, with a pulmonary circuit (heart to lungs and back) and a systemic circuit (heart to body and back). The heart repressurizes blood after it returns from the lungs, so the body receives blood under strong pressure. Birds and mammals have fully separated four chambered hearts, which evolved independently in the two groups; amphibians and most reptiles have some mixing in the ventricle. The four chambered heart evolved independently in birds and mammals.

In mammals, oxygen poor blood from the body enters the right atrium through the venae cavae, passes to the right ventricle, and is pumped through the pulmonary arteries to the lungs. Oxygen rich blood returns through the pulmonary veins to the left atrium, passes to the left ventricle, and is pumped out through the aorta. The left ventricle has the thickest wall because it drives blood through the whole systemic circuit. Atrioventricular valves prevent backflow from ventricles to atria, and semilunar valves prevent backflow from the arteries into the ventricles.

The cardiac cycle and its control

One complete sequence of pumping and filling is the cardiac cycle. Contraction is systole and relaxation is diastole. A normal human blood pressure reading of about 120/80 mm Hg gives systolic over diastolic arterial pressure. Cardiac output, the volume pumped per minute by each ventricle, equals heart rate times stroke volume; at rest about 72 beats per minute times 70 mL is roughly 5 liters per minute, about the entire blood volume.

Cardiac muscle is myogenic: it beats without nerve input. The sinoatrial (SA) node in the right atrium, the pacemaker, sets the rhythm. Its impulse spreads across both atria, which contract together, and reaches the atrioventricular (AV) node, where a delay of about 0.1 second lets the atria finish emptying. The signal then travels down the bundle branches and Purkinje fibers to the apex, so the ventricles contract from the bottom up, squeezing blood toward the arteries. These electrical events produce the electrocardiogram (ECG). Sympathetic nerves and epinephrine speed the pacemaker, and parasympathetic (vagus) nerves slow it.

Gas exchange: the respiratory medium and surface

Gas exchange is the uptake of O2 and release of CO2. Gases move by diffusion down their partial pressure gradients. At sea level, air is about 21 percent oxygen, so the partial pressure of oxygen (P_O2) is about 0.21 × 760 mm Hg, or roughly 160 mm Hg. Water holds far less oxygen than air and is denser, so water breathers must move large volumes across their exchange surface with great efficiency.

All respiratory surfaces are moist, thin and large. Gills are outfoldings of the body surface used by fishes, many mollusks and crustaceans. Fish gills use countercurrent exchange: water flows across the gill lamellae opposite to blood flow, so all along the capillary the blood meets water that is slightly richer in oxygen. This keeps a diffusion gradient along the whole length and allows a fish to extract over 80 percent of the oxygen in the water. Terrestrial vertebrates use lungs, infoldings that keep the moist surface protected from drying.

Mammalian breathing and oxygen transport

In mammals, air enters through the nostrils, is filtered, warmed and humidified, and passes through the pharynx, larynx and trachea, which branches into two bronchi, then into ever finer bronchioles that end in clusters of tiny air sacs, the alveoli. Gas exchange happens across the alveolar walls, which are a single layer of squamous cells pressed against capillaries. A film of surfactant lowers surface tension and keeps alveoli from collapsing; premature infants who lack surfactant develop respiratory distress.

Mammals ventilate by negative pressure breathing. Contraction of the diaphragm (which flattens downward) and the external intercostal muscles enlarges the thoracic cavity, lowering pressure in the lungs below atmospheric pressure, so air flows in. Exhalation at rest is passive as the muscles relax and the elastic lungs recoil.

Breathing is controlled mainly by the medulla oblongata in the brainstem. Surprisingly, the main signal is not low oxygen but rising CO2. CO2 combines with water to form carbonic acid, which lowers the pH of blood and cerebrospinal fluid; sensors detect the drop and the medulla increases the rate and depth of breathing.

Most oxygen travels bound to hemoglobin, a protein of four subunits, each with an iron containing heme group that binds one O2. Binding is cooperative: when one subunit binds oxygen, the others bind more easily, producing an S shaped (sigmoid) dissociation curve. As a result a small drop in P_O2 in active tissue releases a large amount of oxygen. Lower pH, as in active muscle that is producing CO2 and lactate, lowers hemoglobin's oxygen affinity and shifts the curve to the right; this Bohr shift unloads more oxygen exactly where it is needed.

Section 3Immune, excretory and endocrine systems

Innate immunity: the first lines of defense

The body is constantly exposed to pathogens, agents that cause disease, including viruses, bacteria, fungi and parasites. Animal immune systems use two broad strategies. Innate immunity is present in all animals; it is fast, acting within minutes to hours, and recognizes features shared by broad groups of pathogens. Adaptive immunity, found only in vertebrates, is slower on first exposure (days), recognizes specific molecular shapes with enormous precision, and remembers past infections.

Innate defenses begin with barriers: skin, mucous membranes, mucus that traps microbes, cilia that sweep it away, the acid of the stomach, and antimicrobial secretions such as the enzyme lysozyme in tears and saliva, which breaks down bacterial cell walls. Immune cells carry pattern recognition receptors such as the Toll like receptors, which bind molecules common to many microbes and absent from host cells, such as bacterial flagellin, lipopolysaccharide or double stranded viral RNA. Phagocytes, chiefly neutrophils (the most abundant white cells, first to arrive) and macrophages (large, long lived phagocytes that patrol tissues), engulf and destroy microbes. Natural killer cells detect body cells that are infected or cancerous, often because those cells display abnormally few self markers, and trigger their death.

Tissue damage or infection triggers the inflammatory response. Mast cells release histamine, which dilates and leaks local blood vessels; macrophages release signaling proteins called cytokines. More blood, fluid, antimicrobial proteins and phagocytes enter the area, producing the classic signs of redness, heat, swelling and pain.

Adaptive immunity: lymphocytes and antigen recognition

Adaptive immunity depends on two kinds of lymphocytes, both made in the bone marrow. B cells mature in the bone marrow, and T cells mature in the thymus. Each lymphocyte carries thousands of copies of one antigen receptor with a unique binding site. An antigen is any substance that elicits an adaptive response, and the small region of it actually bound by a receptor is an epitope.

Receptor diversity comes from gene rearrangement (V(D)J recombination): each developing lymphocyte randomly joins one of many V, D and J gene segments, generating millions of distinct receptors. Lymphocytes that bind self molecules strongly are removed, producing self tolerance.

B cell receptors and their secreted form, antibodies (immunoglobulins), recognize intact antigens floating free or on pathogen surfaces. An antibody is a Y shaped molecule of two identical heavy chains and two identical light chains; the tips of the Y are the variable regions that bind antigen, and the stem is the constant region that determines what the antibody does next. T cell receptors, by contrast, recognize only fragments of antigen that host cells display on MHC molecules (major histocompatibility complex). Class I MHC, on almost all nucleated cells, displays fragments from inside the cell, such as viral proteins, to cytotoxic T cells. Class II MHC, on antigen presenting cells (dendritic cells, macrophages and B cells), displays fragments of engulfed material to helper T cells.

Clonal selection, the two arms and memory

When an antigen binds the receptor of a matching lymphocyte, that cell is activated and divides repeatedly, producing a clone of identical cells, a process called clonal selection. Some become short lived effector cells that fight the current infection, and some become long lived memory cells. The first encounter produces the primary immune response, which peaks after roughly 10 to 17 days. A later encounter with the same antigen triggers a faster, larger secondary immune response from memory cells, often clearing the pathogen before illness develops. This is the basis of immunological memory and vaccination.

Helper T cells, which carry the CD4 surface protein, are the central coordinators. Activated by an antigen presenting cell, they secrete cytokines that stimulate both arms of adaptive immunity. In the humoral response, activated B cells become plasma cells that secrete antibodies into the blood and lymph. Antibodies do not kill pathogens directly; they neutralize viruses and toxins by blocking binding sites, opsonize microbes (coat them so phagocytes engulf them more readily), clump them together (agglutination) and activate complement. In the cell mediated response, cytotoxic T cells (CD8) recognize infected or cancerous cells by their class I MHC and kill them by releasing perforin, which makes pores, and granzymes, which trigger apoptosis.

Immunity is active when the body makes its own response (infection, vaccination) and passive when ready made antibodies are transferred (across the placenta, in breast milk, or by injection); passive immunity is immediate but fades within weeks because no memory cells form. Failures include allergies, autoimmune diseases such as type 1 diabetes, and immunodeficiencies such as AIDS, in which HIV destroys helper T cells.

Osmoregulation and nitrogenous wastes

Osmoregulation is the control of solute concentrations and water balance. Water moves by osmosis toward the side with higher solute concentration. Most marine invertebrates are osmoconformers, isoosmotic with seawater. Osmoregulators must actively manage the difference. A marine bony fish is hypoosmotic to seawater, so it constantly loses water and gains salt; it drinks seawater, excretes salt through its gills, and makes little, concentrated urine. A freshwater fish is hyperosmotic to its surroundings, so it gains water and loses salt; it drinks almost nothing, makes large volumes of dilute urine, and actively takes up salt through its gills.

Breaking down proteins and nucleic acids releases nitrogen as ammonia (NH3), which is very toxic. Animals excrete nitrogen in one of three forms, and the choice reflects a trade off between water and energy.

Excretory systems and the nephron

Most excretory systems make urine by the same four steps: filtration of body fluid, reabsorption of valuable substances back into the body, secretion of additional wastes into the filtrate, and excretion of the final urine. Vertebrates use kidneys.

Each human kidney contains about a million nephrons. Blood enters a ball of capillaries, the glomerulus, under high pressure, and water and small solutes (glucose, salts, amino acids, urea) are filtered into the cup shaped Bowman's capsule; blood cells and large proteins stay behind. The kidneys filter roughly 180 liters of fluid per day, yet only about 1.5 liters leave as urine, so about 99 percent is reabsorbed. In the proximal tubule, nearly all glucose and amino acids and most of the salt and water are reabsorbed, while drugs, toxins and H+ are secreted. The loop of Henle creates a salt gradient in the kidney medulla: the descending limb is permeable to water but not salt, and the ascending limb is permeable to salt but not water, actively pumping NaCl out in its thick part. This countercurrent multiplier makes the deep medulla very salty. The distal tubule fine tunes K+, NaCl and pH. Finally, filtrate passes down the collecting duct through the salty medulla, and water leaves by osmosis if the duct is permeable, concentrating the urine.

Hormones adjust kidney output. Antidiuretic hormone (ADH, vasopressin), released from the posterior pituitary when blood osmolarity rises, inserts water channels called aquaporins into the collecting duct, so more water is reabsorbed and urine becomes concentrated. When blood pressure or volume falls, the kidney releases renin, starting the renin angiotensin aldosterone system (RAAS). Angiotensin II constricts arterioles and stimulates the adrenal glands to release aldosterone, which increases Na+ reabsorption in the distal tubule and collecting duct; water follows and blood volume rises.

The endocrine system: hormones and their receptors

Hormones are signaling molecules secreted into the blood that act on target cells carrying the matching receptor.

Hormones fall into chemical classes whose solubility determines how they work. Water soluble hormones, which include polypeptides (insulin, glucagon) and amines derived from amino acids such as epinephrine, cannot cross the membrane, so they bind cell surface receptors and act through signal transduction pathways and second messengers such as cyclic AMP; their effects are usually fast changes in existing proteins. Lipid soluble hormones, including steroids (cortisol, estradiol, testosterone, aldosterone) and thyroid hormone, diffuse through the membrane and bind intracellular receptors; the hormone receptor complex acts as a transcription factor, changing gene expression, so effects are slower and longer lasting.

The hypothalamus and pituitary

The hypothalamus in the brain links the nervous and endocrine systems. It controls the pituitary gland, which has two parts. The posterior pituitary is an extension of the brain: hypothalamic neurons make oxytocin and ADH, send them down their axons, and release them into the blood there. The anterior pituitary is true glandular tissue controlled by releasing and inhibiting hormones that the hypothalamus secretes into a small portal blood system. In turn, the anterior pituitary releases tropic hormones that act on other endocrine glands, creating hormone cascades. For example, thyrotropin releasing hormone (TRH) from the hypothalamus causes the anterior pituitary to release thyroid stimulating hormone (TSH), which causes the thyroid to release thyroid hormone (T3 and T4). Thyroid hormone then feeds back to inhibit both the hypothalamus and pituitary, a classic negative feedback loop.

Blood glucose regulation shows antagonistic hormones at work. After a meal, rising glucose stimulates beta cells of the pancreatic islets to release insulin, which promotes glucose uptake by most body cells and glycogen synthesis in the liver, lowering blood glucose. Between meals, falling glucose stimulates alpha cells to release glucagon, which causes the liver to break down glycogen and make new glucose. In type 1 diabetes, an autoimmune attack destroys beta cells, so insulin is absent; in type 2 diabetes, much more common, target cells respond poorly to insulin.

Section 4Nervous systems, sensation and movement

Neurons and nervous system organization

Nervous systems range from the diffuse nerve net of a hydra to the centralized brains of vertebrates and octopuses. Vertebrates have a central nervous system (CNS: brain and spinal cord) and a peripheral nervous system (PNS: nerves and ganglia outside it). Its motor side splits into the somatic system, which controls skeletal muscle, and the autonomic system, whose sympathetic ("fight or flight") and parasympathetic ("rest and digest") divisions control smooth muscle, cardiac muscle and glands.

A neuron receives signals on branched dendrites and its cell body, integrates them at the axon hillock, and sends output down a single axon to synaptic terminals. Glia support neurons; in vertebrates, oligodendrocytes (CNS) and Schwann cells (PNS) wrap axons in an insulating myelin sheath. Gaps in the myelin, the nodes of Ranvier, are where action potentials are regenerated.

The resting membrane potential

Every cell has a voltage across its membrane, inside negative. In a resting neuron it is about -70 mV. Two things create it. The sodium potassium pump uses ATP to move 3 Na+ out for every 2 K+ in, building high K+ inside and high Na+ outside. Then, at rest, many potassium leak channels are open but few sodium channels are. K+ diffuses out down its gradient, leaving behind negatively charged proteins and other anions, until the inside becomes negative enough to hold K+ back. The resting potential therefore sits close to the potassium equilibrium potential (about -90 mV), pulled slightly upward by a small Na+ leak.

The action potential

A stimulus that makes the inside less negative is a depolarization; one that makes it more negative is a hyperpolarization. Small, graded changes fade with distance. But if depolarization at the axon hillock reaches threshold (about -55 mV), voltage gated sodium channels open, Na+ rushes in, and the membrane depolarizes further, opening more channels: positive feedback. The membrane potential spikes to about +30 to +40 mV. Then sodium channels inactivate, and slower voltage gated potassium channels open, so K+ flows out and repolarizes the membrane, briefly overshooting to an undershoot (after hyperpolarization). The action potential is all or none: its size does not depend on stimulus strength. Stimulus strength is coded instead by the frequency of action potentials.

Inactivated sodium channels cannot reopen for a moment, the refractory period, so an action potential travels only away from where it started. Conduction is faster in axons of larger diameter and much faster in myelinated axons, where the action potential jumps from node to node, called saltatory conduction.

Synapses and neurotransmitters

Most synapses are chemical. When an action potential reaches the terminal, voltage gated Ca2+ channels open, Ca2+ enters, and synaptic vesicles fuse with the membrane and release neurotransmitter into the synaptic cleft. The transmitter binds receptors on the postsynaptic cell, often ligand gated ion channels. If they let Na+ in, they produce an excitatory postsynaptic potential (EPSP); if they let Cl- in or K+ out, an inhibitory postsynaptic potential (IPSP). A neuron sums thousands of these inputs over space and time (summation) and fires only if the hillock reaches threshold. The signal ends when transmitter is broken down (acetylcholinesterase destroys acetylcholine) or taken back up into the terminal.

Sensory reception

Sensory receptors convert a stimulus into a change in membrane potential, a step called sensory transduction, producing a receptor potential whose size reflects stimulus strength. Information is coded by which receptors fire (which tells the brain the type and location of the stimulus) and by how often they fire (intensity). Receptors are grouped by the energy they detect.

In the mammalian ear, sound waves vibrate the eardrum and three middle ear bones, which push fluid in the snail shaped cochlea. Vibrations bend the stereocilia of hair cells, opening ion channels. In the vertebrate eye, the lens focuses light on the retina. Rods are very sensitive and work in dim light but do not see color; cones provide color and sharp vision in bright light. Both use a pigment of retinal (made from vitamin A) bound to an opsin protein; light changes retinal's shape, triggering a cascade that, unusually, hyperpolarizes the photoreceptor.

Muscle contraction and movement

A skeletal muscle is a bundle of long, multinucleate muscle fibers, each packed with myofibrils. Myofibrils are chains of repeating units called sarcomeres, the basic contractile units, bordered by Z lines. Thin filaments of actin are anchored at the Z lines; thick filaments of myosin sit in the middle. In the sliding filament model, neither filament shortens; instead the thin filaments slide past the thick ones toward the center of the sarcomere, so the sarcomere shortens.

The power comes from myosin heads. A head hydrolyzes ATP and is "cocked" into a high energy position. It binds actin, forming a cross bridge, then releases ADP and phosphate and pivots in the power stroke, pulling the thin filament. A new ATP binding releases the head from actin, and the cycle repeats. Without ATP, heads cannot detach (rigor mortis).

Contraction is switched on by calcium. At rest, the protein tropomyosin covers the myosin binding sites on actin, held in place by the troponin complex. A motor neuron releases acetylcholine at the neuromuscular junction, triggering an action potential in the muscle fiber that spreads down transverse (T) tubules and causes the sarcoplasmic reticulum to release Ca2+. Calcium binds troponin, tropomyosin shifts, binding sites are exposed and cross bridge cycling begins. When stimulation stops, Ca2+ is pumped back into the sarcoplasmic reticulum, and the muscle relaxes. Force is graded by recruiting more motor units (a motor neuron and all the fibers it controls) and by increasing firing frequency until twitches fuse into sustained tetanus.

Section 5Animal reproduction and development

Asexual and sexual reproduction

In asexual reproduction one parent produces genetically identical offspring by fission (sea anemones splitting), budding (hydra), fragmentation and regeneration (sea stars, some worms) or parthenogenesis, the development of an unfertilized egg (some bees, lizards, aphids). Sexual reproduction combines a haploid egg and sperm into a diploid zygote. It produces genetically varied offspring, which may help populations keep pace with changing environments and evolving parasites.

Fertilization may be external, with gametes released into water as in most fishes and amphibians, or internal, with sperm placed in the female's reproductive tract, an adaptation to life on land.

Gametogenesis in humans

Spermatogenesis occurs continuously in the seminiferous tubules of the testes after puberty. A diploid spermatogonium divides by mitosis; one daughter becomes a primary spermatocyte, which completes meiosis I and II to produce four haploid spermatids that mature into sperm. About 100 million or more sperm are made per day. Oogenesis differs in three ways. It begins before birth, when primary oocytes enter meiosis I and then arrest in prophase I for years. Meiosis is completed one oocyte at a time: after puberty, each cycle an oocyte finishes meiosis I just before ovulation and arrests at metaphase II, completing meiosis II only if a sperm enters. And the divisions are unequal, so each produces one large egg and small polar bodies that degenerate, concentrating cytoplasm in the egg.

Hormones of the reproductive cycles

Reproduction is governed by the hypothalamic pituitary gonadal axis. The hypothalamus releases GnRH, which makes the anterior pituitary release FSH and LH. In males, FSH supports sperm production by Sertoli cells, and LH stimulates Leydig cells to make testosterone, which feeds back negatively on the hypothalamus and pituitary. In females the ovarian cycle and uterine (menstrual) cycle run together over about 28 days. In the follicular phase, FSH and LH stimulate a follicle to grow and secrete estradiol. Low estradiol inhibits the pituitary, but when estradiol rises high enough it switches to positive feedback, producing the LH surge that triggers ovulation around day 14. In the luteal phase, the empty follicle becomes the corpus luteum, which secretes progesterone and estradiol; these maintain the thickened endometrium and inhibit FSH and LH. Without pregnancy the corpus luteum degenerates, hormone levels drop and the endometrium is shed in menstruation. If an embryo implants, it secretes human chorionic gonadotropin (hCG), which keeps the corpus luteum alive; hCG is what pregnancy tests detect.

Fertilization and cleavage

At fertilization, the sperm's acrosome releases enzymes that digest a path through the egg's coats (in mammals the zona pellucida). Fusion of sperm and egg membranes triggers blocks to polyspermy. Fusion also activates the egg's metabolism and, in mammals, completes meiosis II, after which the two haploid nuclei combine.

Cleavage is a series of rapid mitotic divisions without growth, dividing the zygote into many smaller cells called blastomeres. A solid ball of cells, the morula, becomes a hollow blastula with a fluid filled cavity, the blastocoel. In mammals the blastula stage is called the blastocyst, an outer layer, the trophoblast, that will help form the placenta, around an inner cell mass that becomes the embryo itself and is the source of embryonic stem cells.

Gastrulation and organogenesis

Gastrulation rearranges the blastula into a three layered embryo, the gastrula. In a sea urchin, cells at one pole fold inward to form the archenteron (primitive gut), whose opening is the blastopore; in deuterostomes such as sea urchins and vertebrates, the blastopore becomes the anus. The result is three germ layers.

Organogenesis builds organs from the germ layers. In vertebrates, the mesoderm forms a rod, the notochord, which signals the ectoderm above it to thicken into the neural plate. The plate folds into the neural tube, which becomes the brain and spinal cord; failure to close causes spina bifida, whose risk is lowered by folic acid. Mesoderm beside the notochord forms blocks called somites, which give rise to vertebrae and skeletal muscles. Development is driven by cell movement, induction (one group of cells changing the fate of another by signaling), apoptosis (programmed death, which separates fingers), and differential gene expression under Hox genes that specify position along the head to tail axis.

Reptiles, birds and mammals are amniotes: their embryos are surrounded by four extraembryonic membranes, the amnion (fluid filled cushion), chorion (gas exchange), yolk sac and allantois (waste storage). In placental mammals the chorion and maternal tissue form the placenta, where nutrients, gases and wastes are exchanged without the two bloods mixing.

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