Exam 6 Study Guide

Chapters 21 to 24 are the chapters of supply and defense. One system guards the borders. The next two bring in the two things every cell must have, air and food. The last one shows what the cell does with them. These four chapters are heavy on ordered lists and on exact numbers, so this guide puts both in tables you can copy out. Learn the order first, then the values, then the reasoning.

Chapter 21The Lymphatic & Immune System

What to know

Blood vessels are not perfectly sealed. As blood pushes through the capillaries, a little fluid squeezes out into the spaces between cells. About 3 liters a day more leaks out than flows back. If it just pooled you would swell, and your blood volume would crash within hours.

The lymphatic system is the return line. It is a one-way network of vessels that collects the leaked fluid, called interstitial fluid. Once that fluid is inside a lymphatic vessel it gets a new name, lymph, and the system hands it back to the blood near the heart. That is job one, fluid balance.

Job two is fat absorption. The small intestine is lined with special lymph capillaries called lacteals. They soak up fats and fat-soluble vitamins, which are too large to enter blood capillaries directly. The milky fatty lymph they carry is chyle. Job three is immune defense. The lymphatic system houses the lymphocytes and macrophages and filters lymph through checkpoints where those cells can catch invaders.

Lymph starts in lymphatic capillaries, tiny tubes closed at one end. Their wall cells overlap like tiles and act as one-way flaps: fluid can push in but cannot push back out. It flows on into larger lymphatic vessels, which look and act much like veins, with thin walls and inner valves. Along the way it passes through bean-shaped lymph nodes. Then the vessels join into large lymphatic trunks and drain into two collecting ducts. The small right lymphatic duct drains the right arm and the right side of the head and chest. The large thoracic duct drains everything else. Both empty into the subclavian veins at the base of the neck.

Here is the catch. The lymphatic system has no pump of its own. It moves lymph the way veins move blood uphill. The skeletal muscle pump squeezes the vessels as muscles work. The respiratory pump helps through pressure changes with each breath. Smooth muscle in the vessel walls also squeezes in a steady rhythm, and the valves keep all of it going one way. That is why gentle movement lowers swelling, and why a limb that cannot move tends to puff up.

The lymphoid organs fall into two groups by what they do. Primary lymphoid organs are where lymphocytes are born and grow up. Red bone marrow starts all blood cells and matures B lymphocytes. The thymus, a two-lobed organ in the chest, is where T lymphocytes finish maturing and learn not to attack the body's own tissues. The thymus is largest in childhood and slowly shrinks after puberty.

Secondary lymphoid organs are where grown-up lymphocytes meet antigens and launch attacks. An antigen is any marker the immune system sees as foreign. Lymph nodes filter lymph. The spleen filters blood: its red pulp removes worn-out red cells and its white pulp checks the blood for germs. The group also holds the tonsils, the Peyer's patches in the intestine, and MALT, the spread-out tissue that guards every wet surface of the body.

Immunity comes in two styles. Innate or nonspecific immunity is what you are born with. It treats every intruder the same, responds within minutes to hours, and keeps no memory. Adaptive or specific immunity is what you build over a lifetime. It aims at one germ with great precision, takes days to get going the first time, and most importantly it remembers. Those two styles are arranged as three lines of defense, each taking over when the one before it is broken.

The first line is the outer wall: skin, mucous membranes and the fluids they give off. Healthy skin is dry and tough. Mucous membranes trap invaders in sticky mucus, and cilia sweep them out. Chemicals back the wall up. Sweat and skin oil make a mildly sour acid mantle. Tears and saliva hold lysozyme, an enzyme that breaks bacterial walls. Stomach acid kills many germs you swallow. The normal flora, your harmless resident bacteria, crowd out dangerous ones.

The second line meets a germ that got inside. It is still innate and still nonspecific, but now it uses cells and chemicals. Phagocytes swallow and digest invaders, and both neutrophils and macrophages are phagocytes. Natural killer cells destroy virus-infected cells and tumor cells on sight. The line also includes the inflammatory response and fever, plus germ-fighting proteins. Interferons warn nearby cells about viruses. Complement is a chain of blood proteins that punches holes in germs and tags them for destruction.

The third line is adaptive immunity: the lymphocytes, which are the T cells and B cells, plus the antibodies B cells make. It is slow to start but extremely exact, and it leaves behind memory cells so the next attack is faster and stronger. Only the third line has memory.

Cut your finger and within minutes it turns red, warm, swollen and sore. Those are the four cardinal signs, in Latin rubor, calor, tumor and dolor. They are not the infection. They are the inflammatory response, a key weapon of the second line, and it has three goals: clear debris and germs, wall off the hurt area, and set the stage for repair.

Damaged cells and nearby mast cells send out alarm signals, the best known being histamine, along with prostaglandins. Those chemicals do two things. They cause vasodilation, so more blood rushes in, which makes the redness and the heat. They also make capillary walls leakier, so fluid, clotting proteins and defense cells seep into the tissue, which makes the swelling. Swelling pressure on nerve endings, plus the chemicals themselves, makes the pain.

Then the cleanup crew arrives. Signals from the injury draw phagocytes toward it, which is chemotaxis. Neutrophils come first, squeezing out through the vessel wall in a step called diapedesis. Longer-lived macrophages come next and eat germs and dead cells. Thick creamy pus is just the leftover mess: dead neutrophils, broken tissue and destroyed germs.

Inflammation can go body-wide. When infection is widespread, chemicals called pyrogens reset the hypothalamus to a higher setting, which causes fever. A moderate fever slows the growth of many germs and speeds repair. The marrow also makes more white cells, which is leukocytosis, and that is why a high white-cell count hints at infection.

The third line splits in two branches. Cell-mediated immunity is run by T lymphocytes and deals with threats that hide inside your cells: viruses, some bacteria and cancer cells. T cells work by direct cell-to-cell contact, not with antibodies. They are born in bone marrow but finish growing up in the thymus, where only cells that leave your own tissues alone are allowed to graduate.

Here is the key rule. A T cell is blind to free-floating antigen. It can only see an antigen when another cell holds it up on its surface in a display molecule called an MHC. Every cell with a nucleus carries MHC class I and uses it to show samples of the proteins it is making inside. A healthy cell shows normal proteins; a virus-infected cell shows bits of virus, in effect raising a flag that says it is infected. Antigen-presenting cells, which are dendritic cells, macrophages and B cells, also carry MHC class II and use it to show bits of germs they have swallowed. This need for presentation is a safety switch that keeps the powerful T-cell response from firing at random.

Each T cell has a receptor that fits one antigen. When a T cell meets the presented antigen that matches it, that one cell is chosen to multiply into an army of identical copies. That is clonal selection. The helper T cell, marked CD4, is the coordinator: it reads antigen on MHC II and releases cytokines that switch on cytotoxic T cells, B cells and macrophages. Without those signals neither cytotoxic T cells nor B cells fully switch on. The cytotoxic T cell, marked CD8, is the killer: it reads antigen on MHC I, releases perforin to punch a hole in the target and then sends in granzymes that make the cell destroy itself. Regulatory T cells calm the response and shut it down, which prevents autoimmunity. Memory T cells last for years.

The other branch is humoral immunity, named from humor, an old word for body fluid. It is the job of B lymphocytes. T cells attack threats hidden inside cells; B cells fight germs floating free in blood, lymph and tissue fluid, and they do it by making antibodies. B cells mature in red bone marrow, which is easy to hold: B is for bone marrow. Then they wait in the lymph nodes and spleen for their matching antigen.

When a B cell's receptor locks onto its antigen, usually with a push of cytokines from a helper T cell, it switches on and divides fast into two kinds of cells. Most become plasma cells, short-lived antibody factories that each pump out thousands of identical antibodies every second. The rest become memory B cells that stay for years.

An antibody is a Y-shaped protein, also called an immunoglobulin. It is built from four chains, two heavy and two light. The two tips of the Y form the variable region, a custom-shaped antigen-binding site that fits one antigen like a key fits a lock. The stem is the constant region, which sets the class. Antibodies usually do not kill a germ outright. They tag and disable it four ways. They neutralize toxins and viruses by covering the part that would stick to your cells. They agglutinate, clumping germs so they are easy to clear. They activate complement, which bursts the invader. And they opsonize, coating the target so phagocytes can grab it.

The first time you meet a germ you get a primary response. It is slow, taking several days to find the right B cell, multiply it and start making antibody, mostly IgM first and then IgG. You may get sick in the meantime. That meeting leaves memory B cells. If the same germ returns you get a secondary response, much faster and stronger, with a flood of high-quality IgG within a day or two, often clearing the invader before you feel sick. That difference is the whole idea behind vaccination.

Acquired immunity sorts on two questions. First, who made the antibodies? If your own immune system made them, it is active: slow to build but lasting, because it comes with memory cells. If you received ready-made antibodies from someone else, it is passive: protective right away but only for a while, because the borrowed antibodies break down and no memory cells replace them. Second, how did the exposure happen? Through everyday life it is natural. Through medicine it is artificial. Combine the two questions and you get four types.

Worth memorizing

How to reason through the question types

The traps people fall into

Chapter 22The Respiratory System

What to know

The airway splits into two working zones. The conducting zone is the plumbing: nose, pharynx, larynx, trachea, bronchi and bronchioles. These tubes carry air but never trade gases. The respiratory zone is where oxygen is actually traded for carbon dioxide: respiratory bronchioles, alveolar ducts and alveoli. Think of the conducting zone as the highway and the respiratory zone as the destination.

Doctors also split the tract by place. The upper respiratory tract is everything above the larynx: nose, nasal cavity, sinuses and pharynx. The lower respiratory tract is the larynx and everything below: trachea, bronchi and lungs. That is why a cold feels different from bronchitis. A cold is an upper-tract infection; the others are lower-tract problems.

Follow one breath. Air enters the nostrils and swirls through the nasal cavity, then the pharynx, which has three parts. It slips through the larynx, the voice box, guarded by a flap called the epiglottis that flips down when you swallow so food goes to the esophagus. Then it enters the trachea, held open at all times by C-shaped cartilage rings. The trachea splits into the right and left primary bronchi, which branch again and again into smaller bronchi and then bronchioles, ending in clusters of alveoli. The whole branching pattern is the bronchial tree.

By the time air reaches the alveoli it has been warmed to body heat, filled with water vapor and scrubbed almost clean. The nasal cavity does most of this: its rich blood supply gives off heat and its mucous lining traps dust and germs. Under that mucus sits a carpet of cilia that beat in waves toward the throat. That is the mucociliary escalator, which sweeps trapped dirt up and out to be swallowed or coughed away.

Your lungs hold about 300 million alveoli. Each is a hollow sac wrapped in a mesh of capillaries. One alone is tiny, but spread out their walls would cover about 70 square meters, roughly the floor of a small apartment. That huge area is the whole point: the more surface, the more gas can cross at once.

Gases cross the respiratory membrane, the barrier between alveolar air and capillary blood. It is only about 0.5 micrometers thick, thinner than a soap bubble, and it has just three layers: the alveolar wall, a single flat layer of type I cells; the fused basement membranes glued together; and the capillary wall, a single flat layer of lining cells. Thinness matters because gases cross much more slowly through a thicker barrier. In pulmonary edema fluid floods the membrane and in pulmonary fibrosis scar tissue stiffens it. Oxygen then has farther to travel, and the person is short of breath even though air and blood are both right there.

A bubble with wet walls tends to collapse, because the water molecules lining it pull toward each other. That pull is surface tension. Left alone it would snap the smallest alveoli shut every time you breathed out. So type II alveolar cells release surfactant, a soapy mix of fats and proteins that coats the inside of the sacs, breaks up the water's pull and keeps them open and easy to fill.

You do not suck air in. You make your chest bigger and air rushes in to fill the space. The physics is Boyle's law: at a steady temperature, a gas's pressure rises when its volume falls and falls when its volume rises. Air always flows from higher pressure to lower, so your muscles only have to change the size of your chest.

Inspiration is active. The diaphragm, a dome of muscle under the lungs, tightens and flattens downward. At the same time the external intercostals lift the ribs up and out. Both enlarge the thoracic cavity, which lowers the intrapulmonary pressure just below the outside air, so air flows in until the pressures are equal. The lungs have no muscle of their own; they follow the chest wall, held to it by a thin film of fluid and by the intrapleural pressure, which always stays negative. Break that seal and the lung collapses, which is a pneumothorax.

Quiet expiration is passive. The diaphragm and external intercostals simply relax, and the stretched lungs and chest wall recoil like a released rubber band. The chest gets smaller, pressure inside rises above the outside, and air flows out. Only forced breathing out, as in blowing out candles, coughing or hard exercise, brings in the internal intercostals and abdominal muscles.

In a mix of gases each gas adds its own share to the total pressure, and that share is its partial pressure. Oxygen makes up about 21 percent of air, so at sea level its partial pressure in open air is about 160 mmHg. Inside the alveoli it mixes with other gases and falls to about 104 mmHg. The rule that follows is the one rule of all gas exchange: a gas moves from where its partial pressure is high to where it is low, and stops when the two sides even out.

External respiration is the swap in the lungs. Blood coming back from the body has a P O₂ of about 40 mmHg and a P CO₂ of about 45 mmHg. Alveolar air is the reverse, about 104 and about 40 mmHg. So oxygen moves down its gradient into the blood and carbon dioxide moves out into the alveoli to be breathed out. Blood leaves fully loaded with oxygen but has given up only a small part of its carbon dioxide, just enough to bring P CO₂ from about 45 down to about 40. Most of its carbon dioxide stays in a large bicarbonate pool, and each trip through the lungs trims that pool without emptying it.

Internal respiration is the same physics run backward out in the tissues. Cells burn oxygen and give off carbon dioxide, so tissue P O₂ is low, about 40 mmHg, and tissue P CO₂ is high, about 45 mmHg. The arriving blood is the opposite, so oxygen moves out into the cells and carbon dioxide moves into the blood for the trip back.

Oxygen barely dissolves in water, so plasma alone could never carry enough. Only about 1.5 percent is dissolved; the other 98.5 percent is bound to hemoglobin, the iron-containing protein packed inside red cells. Each hemoglobin holds up to four oxygen molecules on its iron sites, and loaded hemoglobin is oxyhemoglobin. Hemoglobin lets blood carry about seventy times more oxygen than it could without it.

Graph how full hemoglobin is against the surrounding P O₂ and you get an S-shaped line, the oxygen–hemoglobin dissociation curve. Hemoglobin grabs oxygen tightly where oxygen is plentiful, in the lungs, and lets it go where oxygen is scarce, in the tissues. Better still, it answers what the tissue needs. A hard-working tissue is warmer, more acidic and fuller of carbon dioxide, and there hemoglobin loosens its grip. The shift caused by low pH and high carbon dioxide is the Bohr effect. Warmth shifts the curve the same way, but through a separate path.

Carbon dioxide takes three rides back. About 7 percent dissolves in plasma. About 23 percent binds hemoglobin as carbaminohemoglobin, on a different spot than oxygen uses. Most of it, about 70 percent, is turned into bicarbonate inside red cells. The enzyme carbonic anhydrase joins carbon dioxide with water to make carbonic acid, which splits into a hydrogen ion and a bicarbonate ion, and the bicarbonate slips out into the plasma. At the lungs the whole reaction runs in reverse, freeing carbon dioxide to be breathed out. This is what ties breathing to blood pH.

A spirometer records how much air you move. Its tracing splits into four volumes. Tidal volume is one normal quiet breath, about 500 mL. Inspiratory reserve volume is the extra you can pull in with your deepest breath, about 3000 mL. Expiratory reserve volume is the extra you can force out after a normal breath out, about 1100 mL. Residual volume is the air that always stays behind, about 1200 mL, and it keeps the alveoli from collapsing between breaths. A simple spirometer cannot measure it.

A capacity is two or more volumes added together. Vital capacity is tidal plus inspiratory reserve plus expiratory reserve, about 4600 mL, and it is the number doctors care about most. Total lung capacity adds residual volume back in, about 5800 mL. Inspiratory capacity is tidal plus inspiratory reserve. Functional residual capacity is expiratory reserve plus residual volume, which is what is left after a normal breath out.

Not all inhaled air reaches the alveoli. About 150 mL stays in the conducting airways where no gas exchange happens, and that is the anatomical dead space. So of a 500 mL breath, only about 350 mL does real work. Spirometry becomes powerful when it is timed. The FEV₁/FVC ratio tells how much of the vital capacity you can blow out in the first second, and it separates the two big families of lung disease. In obstructive disease, such as asthma and COPD, the airways are narrow, air comes out slowly, and the ratio drops. In restrictive disease, such as fibrosis, the lungs are stiff and small, so the volumes shrink but the air that is there comes out quickly, and the ratio stays normal or high.

Worth memorizing

How to reason through the question types

The traps people fall into

Chapter 23The Digestive System

What to know

The digestive system has two groups of organs. The alimentary canal, also called the GI tract, is the one long muscle tube food actually passes through: mouth, pharynx, esophagus, stomach, small intestine, large intestine, anus. Laid out end to end it runs about nine meters, though muscle tension keeps it shorter in a living person. The accessory organs are the helpers food never passes through: teeth, tongue, salivary glands, liver, gallbladder, pancreas. Some help by physical work and others pour juices into the tube through ducts.

Everything the system does fits six essential processes. Ingestion takes food in. Propulsion moves it along, first by swallowing on purpose and then by waves of muscle called peristalsis. Mechanical digestion breaks food into smaller bits by physical force, which gives enzymes more surface. Chemical digestion uses enzymes to split big molecules into small ones. Absorption moves the small molecules across the gut wall into blood or lymph. Defecation gets rid of what cannot be taken in. A seventh word, secretion, runs through all six: water, acid, enzymes, bile and mucus are released along the way.

From the esophagus to the anus the tube is built from the same four layers. The innermost is the mucosa, the moist lining that makes juices and takes in food, facing the hollow centre called the lumen. Around it is the submucosa, connective tissue full of blood vessels, lymph vessels and a nerve web. Next is the muscularis externa, usually two sheets of smooth muscle, an inner sheet in rings and an outer sheet along the length. The outermost is the serosa, also called the visceral peritoneum, on organs that hang free in the belly. Where an organ is fixed to the body wall, as the esophagus is, the outer layer is instead a tough adventitia.

The two muscle sheets make two very different movements. The inner ring muscle narrows the tube when it squeezes. The outer lengthwise muscle shortens it. By timing them, the gut can push a lump along or churn it in place. Peristalsis is a travelling wave of squeezing that pushes food forward: just behind the lump, called a bolus, the ring muscle squeezes, and just ahead of it the muscle relaxes to make room. It is strong enough to work against gravity, so you can swallow lying down. Segmentation is a mixing rhythm with little forward motion, mostly in the small intestine. Rings squeeze here and there, chopping the contents into sections and sloshing the chyme back and forth. That blends food with enzymes and presses it against the wall so nutrients can be taken in. Only when most of the food is absorbed does segmentation give way to peristalsis. Pacemaker cells called the interstitial cells of Cajal set the beat for both. Thick rings of muscle called sphincters act as one-way gates between parts of the tube.

The stomach is a J-shaped bulge with four regions. The cardia is where the esophagus enters. The fundus is the dome beside it. The body is the large middle. The pylorus is a funnel narrowing to the pyloric sphincter at the exit. When empty, the lining lies in deep folds called rugae that flatten as it fills, letting it hold a liter or more. The stomach also has a third muscle layer the rest of the tube lacks, an inner oblique layer running at a slant, which lets it churn in many directions and grind a meal into chyme.

The lining is dotted with gastric pits leading down into gastric glands, and different cells line them. Surface mucous cells make a thick mucus rich in bicarbonate that shields the lining from acid. Mucous neck cells, deeper in the gland's neck, make a different mucus that is thinner and a little acidic, and it is not the protective coat. Parietal cells pump out hydrochloric acid and also make intrinsic factor. Chief cells release pepsinogen, the inactive form of the protein-splitting enzyme pepsin, plus a little gastric lipase. Enteroendocrine cells make hormones; the G cells release gastrin, which tells the other cells to make their juices. Together they make two to three liters of stomach juice a day.

Parietal cells drive the stomach pH down to about 1.5 to 2, strong enough to unfold proteins and to turn pepsinogen into active pepsin. Acid release runs in three overlapping phases. The cephalic phase starts in the brain when you see, smell or think about food. The gastric phase starts when the stomach stretches and meets protein, and it is the largest. The intestinal phase begins as chyme moves on; it first boosts acid release briefly, then calms it down.

So why does the stomach not digest itself? Its mucosal barrier protects it three ways: a thick coat of bicarbonate-rich mucus, tight junctions sealing the lining cells to each other, and replacement of the surface cells every few days.

The small intestine is where almost all chemical digestion finishes and almost all food is taken in, so nearly everything about it is built for surface. It has three parts in order. The duodenum is short and curved, and it receives chyme from the stomach plus bile and pancreatic juice. The jejunum is long and is the main absorbing stretch. The ileum finishes the job and empties into the large intestine at the ileocecal valve.

The tube is only about an inch wide, but three levels of folding turn its length into a surface roughly the size of a tennis court, around 200 square meters. First, the wall has lasting ridges called circular folds that make chyme spiral slowly along, giving more time and contact. Second, every fold is covered with millions of tiny fingers called villi, each about a millimeter tall. Third, each cell on a villus carries thousands of tiny bumps on its top edge, the microvilli, packed so tight they look furry. That fuzzy edge is the brush border. Together the three levels make the surface more than 500 times bigger than a flat tube.

Zoom in on one villus and you find the whole machine in miniature. Its outer layer is a sheet of absorptive epithelial cells carrying the brush border, and enzymes on that border finish breaking down sugars and small protein bits right where they are taken in. Inside is a web of capillaries that carry sugars and amino acids off to the liver. In the centre is one closed-end lymph vessel, the lacteal, which takes in digested fats. Between the villi are deep pits called intestinal crypts that keep making new cells to replace the ones worn off the tips, which is why the lining renews itself every few days. Destroy the villi, as celiac disease does, and absorption fails.

The helper glands pour juice in from the side. The salivary glands are the parotid in front of each ear, the submandibular under the jaw and the sublingual under the tongue, and together they release up to a liter and a half of saliva a day. Saliva wets food into a swallowable bolus, starts starch digestion with salivary amylase, and guards the mouth with lysozyme and antibodies.

The liver is the body's largest gland, with dozens of jobs, but its one digestive job is to make bile. Bile holds bile salts, which act on fat the way dish soap acts on grease: they emulsify it, breaking big blobs into many tiny droplets so fat-digesting enzymes have far more surface. Between meals bile flows into the gallbladder, a small muscular pouch that stores it and makes it stronger. When a fatty meal reaches the duodenum, the hormone cholecystokinin tells the gallbladder to squeeze, and bile flows down the common bile duct.

The pancreas sits behind the stomach and does two jobs. Its exocrine part uses acinar cells to make pancreatic juice, the most complete digestive juice in the body, with an enzyme for every food group: pancreatic amylase for starch, lipase for fat, trypsin and chymotrypsin for protein, and nucleases for nucleic acids. The juice also carries plenty of bicarbonate, which cancels the acid arriving from the stomach so intestinal enzymes can work at a near-neutral pH. Its endocrine part, the pancreatic islets, releases insulin and glucagon into the blood. The pancreatic duct joins the common bile duct at the hepatopancreatic ampulla, and their mixed flow enters the duodenum through a ring of muscle called the sphincter of Oddi.

Most nutrients arrive as big long chains too large to cross a cell membrane. Chemical digestion fixes that by hydrolysis, splitting with water: enzymes cut the bonds and add a molecule of water at every cut, until only small building blocks are left.

Carbohydrate digestion starts in the mouth with salivary amylase and picks up in the small intestine with pancreatic amylase, both breaking starch into maltose and other small pieces. Then brush-border maltase, sucrase and lactase split those two-part sugars into single sugars: glucose, fructose and galactose. Protein digestion begins in the stomach with pepsin, goes on in the intestine with trypsin and chymotrypsin, and is finished by brush-border peptidases that free single amino acids. Nucleic acids are cut by pancreatic nucleases into nucleotides, then brush-border nucleosidases and phosphatases take those apart into nitrogenous bases, pentose sugars and phosphate ions, and those pieces are what is taken in.

Fat is the special case, because it does not mix with watery chyme. Bile salts must emulsify it into tiny droplets first. Only then can pancreatic lipase cut each triglyceride into monoglycerides and free fatty acids. Little bundles of bile salts called micelles carry them to the villus surface and they pass into the gut cell. Inside, they are put back together into triglycerides, coated in protein and shipped out as droplets called chylomicrons. Those are too big for the capillaries, so they go into the lacteal instead. That is why fat from food travels through the lymph first, while sugars and amino acids go straight to the liver in the blood.

Worth memorizing

How to reason through the question types

The traps people fall into

Chapter 24Metabolism & Nutrition

What to know

Metabolism is the sum of every chemical reaction in the body, and each one sorts into one of two directions. Anabolism is the building direction: small molecules are joined into bigger ones, usually by dehydration synthesis, where a water molecule is removed to form a bond. Amino acids become proteins, glucose units become glycogen, fatty acids and glycerol become fat. Building costs energy, so anabolic reactions are endergonic: they take energy in and must be paid for.

Catabolism is the breaking-down direction: big molecules are split into smaller ones, usually by hydrolysis, where water is added to break a bond. That frees the energy locked in those bonds, so these reactions are exergonic: they pay out. The two directions work as a team, because the energy catabolism frees is exactly what pays for anabolism.

The body does not spend food energy directly. It turns that energy into one kind of money every cell uses, ATP. ATP holds its energy in the bonds between its three phosphate groups. Snap off the last phosphate and you get ADP, a free phosphate and a burst of energy the cell can use for muscle movement, nerve signals and building work. Catabolism then recharges the battery by sticking the phosphate back on. Linking a reaction that gives off energy to one that needs energy is energy coupling, and it is what keeps the energy from being lost as heat. You cycle about your whole body weight in ATP each day, not because you store that much but because each molecule is recharged thousands of times.

Many reactions in metabolism are oxidation-reduction reactions, where electrons move from one molecule to another. A molecule that loses electrons is oxidized; one that gains them is reduced. This matters because electrons carry energy. The cell moves them with shuttle molecules called electron carriers, mainly NAD⁺ and FAD. When they pick up electrons they become NADH and FADH₂, loading up energy to deliver later.

Cellular respiration is the careful, step-by-step breakdown of glucose to make ATP. It is a slow, safe burn: the cell takes the energy away in small steps and saves it in ATP as it goes, instead of freeing it all at once. It has four stages in two places. The first happens in the cytoplasm and the last three inside the mitochondrion. With enough oxygen, one glucose molecule can make up to about 30 to 32 ATP.

Glycolysis happens in the cytoplasm and needs no oxygen. One glucose, with six carbons, is split into two pyruvate molecules of three carbons each. The cell spends 2 ATP to start and gets 4 back, a net gain of 2 ATP, plus 2 NADH.

Pyruvate oxidation, also called the transition reaction, moves each pyruvate into the matrix, the inner space of the mitochondrion. One carbon is cut off and leaves as CO₂, and the rest is joined to a carrier to form acetyl CoA. This step makes more NADH.

The citric acid cycle, also called the Krebs cycle, also runs in the matrix. Acetyl CoA is fed into a loop that frees the rest of the carbons as CO₂, makes a little ATP directly, and most importantly loads up many NADH and FADH₂ carriers.

Oxidative phosphorylation happens on the inner membrane of the mitochondrion, and this is the big payoff. The loaded carriers drop their electrons into the electron transport chain, which uses that energy to pump H⁺ ions across the membrane and build up a crowd on one side. The ions then rush back through an enzyme that spins like a water wheel, and as it spins it snaps phosphates onto ADP. This stage alone makes most of the ATP, about 26 to 28.

Here is the big point. Oxygen is the final electron acceptor. At the very end of the chain the used-up electrons and some H⁺ ions are handed to O₂, forming water. If no oxygen is there to take them, the chain backs up like a clogged drain, the carriers stay loaded, and stages two through four grind to a stop. The cell then falls back on anaerobic fermentation, keeping glycolysis going by turning pyruvate into lactic acid. That frees up the NAD⁺ glycolysis needs and gives a fast trickle of 2 ATP with no oxygen, which helps a sprinting muscle. It is very wasteful, and the lactic acid builds up.

Your fuel supply is not steady. It arrives in bursts at mealtimes and then runs low for hours, so the body runs in two metabolic states. The absorptive or fed state is the few hours after a meal, when nutrients pour in and blood sugar rises. The job is to store: extra glucose is packed into glycogen, which is glycogenesis; extra fuel is turned into fat, which is lipogenesis; amino acids build protein.

The postabsorptive or fasting state takes over once the meal is fully taken in, which happens overnight, between meals or during a fast. The job flips to releasing stored fuel to keep blood sugar steady. Glycogen is broken back down to glucose, which is glycogenolysis. Fat is broken down, which is lipolysis. The liver even makes brand-new glucose from things that are not carbs, such as amino acids, which is gluconeogenesis.

Two pancreatic hormones run the switch, and they work against each other. Insulin is the storage hormone: it rises after a meal, moves glucose into cells and turns on the building pathways. Glucagon is the releasing hormone: it rises during fasting and turns on the pathways that free stored fuel. Think of them as a seesaw, high insulin for store and high glucagon for spend. One organ is the hub for all of it, the liver, which stores glycogen after meals and sends out glucose between them.

Why go to all this trouble? Because the brain runs almost only on glucose and cannot store its own fuel, so blood sugar must never crash. During a long fast the body uses glucose sparing: most tissues switch to burning fatty acids, which saves the scarce glucose for the brain. In long starvation the liver turns fat into ketone bodies, a backup fuel the brain can partly use. It is clever, but ketones are acidic and a large buildup can make the blood dangerously acidic.

Everything worth eating falls into six nutrient classes. Three give usable energy and are eaten in large amounts, so they are the macronutrients: carbohydrates, lipids and proteins. The other three give no energy but are needed in smaller amounts: vitamins, minerals and water. No energy does not mean skippable. Without water or tiny amounts of certain minerals you would die long before you starved.

Food energy is measured in kilocalories, written on labels as Calories with a capital C. Only the three macronutrients have calories, and they are not equal. Carbs and protein each give about 4 kcal per gram. Fat gives more than twice that, about 9 kcal per gram, which is why fatty foods are so high in calories and why the body picks fat for long-term storage. Alcohol is not a nutrient but still carries about 7 kcal per gram.

An essential nutrient is one your body cannot make, or cannot make enough of, so it must come from food. These include about nine essential amino acids, a couple of essential fatty acids, and all the vitamins and minerals. That is why protein quality matters. A complete protein has all the essential amino acids, as meat, eggs, dairy and soy do. Most single plant foods are incomplete, but combining plants that fill each other's gaps, like beans with rice, gives the full set.

Vitamins are carbon-based molecules needed in very small amounts to run metabolism, and most act as coenzymes, helper molecules enzymes need in order to work. You need only milligrams or even micrograms a day, yet being short on even one can cause a specific disease. One simple thing controls how a vitamin behaves: how it dissolves.

The fat-soluble vitamins are A, D, E and K. Because they dissolve in fat they are taken in with the fat in your food and then stored in the liver and fat tissue. Storage cuts both ways: you can go a while without them, but the body cannot easily flush out the extra, so very large doses of A or D can build up to toxic levels. A helps you see, D balances calcium and builds bone, E is an antioxidant that protects cells, and K helps blood clot.

The water-soluble vitamins are the B-complex and vitamin C. Because they dissolve in water the body does not stock up on them; the kidneys filter out the extra and it leaves in urine. The downside is that you need a steady daily supply, and problems show up fairly fast when you do not get enough. Most B vitamins are coenzymes in the energy pathways. The classic shortage diseases are worth knowing: scurvy from too little vitamin C, rickets from too little D, beriberi from too little B₁, pellagra from too little B₃, and pernicious anemia from too little B₁₂.

Body weight follows a money-like rule called energy balance, comparing calories in as food with calories spent. When they match, weight holds steady, which is neutral balance. When intake is greater, the extra is stored mostly as fat and weight rises, which is positive balance. When spending is greater, the body draws on stores and weight falls, which is negative balance. The rule is simple; the control is hard, because biology runs both sides of the ledger.

Energy out is not just exercise. It has three parts. By far the largest is the basal metabolic rate, the energy burned just to stay alive at rest, keeping the heart beating, the kidneys filtering and the body warm. It makes up about 60 to 75 percent of a day's total. A second part, about 10 percent, is the thermic effect of food, the energy spent digesting and taking in a meal. The last part varies most: physical activity, from fidgeting to running a marathon. Because BMR is the biggest part, things that change it matter a lot: muscle mass, age, thyroid hormone and body size.

Energy balance is controlled like any other steady value. The hypothalamus is the control center. It reads hormone signals about stored fuel. Leptin from fat tissue signals that stores are full and turns down hunger. Ghrelin from the empty stomach signals hunger. A useful rule of thumb is that a pound of body fat stores about 3,500 kcal, so eating about 500 kcal less than you burn each day takes off close to a pound a week, at least until the body lowers its BMR to fight the loss.

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