Exam 7 Study Guide

Chapters 25 to 28 close the book. Two of them are about holding the inside of the body steady, down to the last drop of water and the last unit of acid. Two of them look past you, to the next person. These chapters reward exact order more than any others in the book. Learn the path through the nephron, the four acid-base boxes, the phases of the cycle and the three germ layers. Then the reasoning comes easily.

Chapter 25The Urinary System

What to know

It is easy to call the urinary system a waste line. That sells it short. Yes, the kidneys clear nitrogen wastes: urea from breaking down protein and creatinine from muscle. But their bigger job is homeostasis. Minute by minute they decide how much water, sodium, potassium, calcium and acid to keep and how much to let go. They also help set blood pressure, tell the marrow to make red blood cells, and turn on vitamin D.

The plumbing is simple. Two kidneys make urine. Two ureters carry it down. One urinary bladder stores it. One urethra carries it out. Everything up to the ureters is about chemistry, changing the blood. Everything from the ureters down is about moving and storing. The kidneys sit high on the back wall of the belly and are retroperitoneal, meaning behind the lining of the belly rather than inside it. The right kidney sits a little lower, because the large liver is above it.

The kidneys handle a huge amount of blood, about 20 to 25 percent of the cardiac output, more for their size than almost any other organ. From it they filter about 180 liters a day. If all of that left as urine you would die quickly, so the kidney takes back more than 99 percent and only about 1 to 2 liters leave. That plan is the secret of its control: push a huge amount out, then pick exactly what to take back, so dozens of substances can be set one at a time.

Slice a kidney like a bean and the layers are neat. A tough renal capsule wraps the outside. Under it is the grainy renal cortex, where filtering starts. Deeper is the renal medulla, made of 8 to 18 cone-shaped renal pyramids pointing inward. The tip of each cone is a renal papilla, which drips finished urine into the collecting spaces. Strips of cortex called renal columns dip between the pyramids and carry blood vessels. The whole kidney curves around a notch on its inner edge, the hilum, where the renal artery comes in and the renal vein and ureter go out.

Once urine drips off a papilla the kidney never changes it again; it is only collected and drained. That route names the parts a kidney stone passes. Urine leaves the papilla into a cup-shaped minor calyx. Several join to form a major calyx. The major calyces empty into a funnel, the renal pelvis, which narrows at the hilum and becomes the ureter.

The kidney's blood supply has one odd feature that makes everything else work. Most organs have one capillary bed; the kidney has two in series. Blood comes in through the renal artery, branches down to a tiny afferent arteriole and enters the first bed, a high-pressure knot of capillaries called the glomerulus, where filtering happens. It does not drain into a vein next. It leaves through an efferent arteriole and enters a second bed, the peritubular capillaries wrapped around the tubules. Two beds let the kidney filter under high pressure first and take things back under low pressure second.

The kidney does not filter like one big strainer. Its work is split among about one million nephrons in each kidney, each a whole little urine factory. A nephron has two parts: a renal corpuscle that makes the filtrate, and a long winding renal tubule that turns filtrate into urine.

The renal corpuscle is the glomerulus sitting inside a cup called the glomerular capsule, also called Bowman's capsule. Fluid squeezes out of the blood and crosses a three-layer filtration membrane. The first layer is the fenestrated capillary wall, full of pores. The middle layer is a basement membrane with a negative charge that pushes proteins away. The third layer is made of octopus-like cells called podocytes, whose feet lock together and leave narrow filtration slits. Together they let water and small particles pass easily while holding back blood cells and blood proteins. So normal filtrate is basically blood plasma with no protein, and protein or blood in the urine is a warning that this membrane may be damaged.

From the capsule, filtrate flows through the tubule in a set order. First is the proximal convoluted tubule, where proximal means near and convoluted means twisted. Next is the hairpin-shaped loop of Henle, with a part going down and a part going up. Then the distal convoluted tubule, where distal means far. Last is the collecting duct, which gathers filtrate from many nephrons and carries it toward the papilla. Most nephrons sit almost fully in the cortex. A smaller group, the juxtamedullary nephrons, have long loops that dive deep into the medulla, and they are what make concentrated urine possible.

The plan for making urine looks wasteful but is very smart: dump almost everything out, then take back what you want. It runs in three steps. Glomerular filtration pushes a large amount of fluid from blood into the tubule. Tubular reabsorption takes water and useful substances back into the blood. Tubular secretion moves a few extra wastes and ions from blood into the tubule to be thrown out. Whatever is left in the tubule after all three is the urine.

Filtering is driven by pressure alone. Blood enters the glomerulus under high pressure because a wide afferent arteriole feeds in and a narrow efferent one drains out, like a thumb over the end of a hose. All the glomeruli together make filtrate at the glomerular filtration rate, normally about 125 mL per minute, which adds up to about 180 L a day. GFR is a vital sign for the kidney, and a falling GFR is the main measure of kidney failure. The kidney guards it closely by widening or narrowing the afferent and efferent arterioles, so filtering stays steady even as blood pressure moves.

Reabsorption is what saves you. The proximal convoluted tubule alone takes back about 65 percent of the filtered water and sodium, plus almost 100 percent of the glucose and amino acids, which are too valuable to waste. The loop of Henle makes the medulla salty, and later that salt pulls water back by osmosis. By the collecting duct only small changes are left. Meanwhile secretion runs the other way, moving hydrogen ions to control pH, extra potassium, and many drugs and poisons from the blood into the tubule. Secretion is how the kidney clears things that do not filter well.

The kidney does not decide alone how much water to keep. The main water hormone is antidiuretic hormone, also called vasopressin, and antidiuretic means against making lots of urine. When you are low on water the blood gets too concentrated, the hypothalamus senses it, and the back of the pituitary releases ADH. ADH acts on the collecting duct, putting water channels called aquaporins into its wall. Water then flows out into the salty medulla, so you pass a small amount of concentrated urine and save water. With plenty of water ADH drops, the channels are removed, and you pass a large amount of dilute urine. Alcohol blocks ADH, which is why a night of drinking leaves you dried out.

To control blood pressure the kidney manages sodium, because where sodium goes water follows, more water means more blood volume, and more volume means higher pressure. The main system is the renin–angiotensin–aldosterone system. When pressure drops, the kidney's granular cells release renin. Renin changes a liver protein into angiotensin I. Then an enzyme in the lungs, ACE, changes it into angiotensin II. Angiotensin II is powerful two ways. It squeezes blood vessels narrower, which raises pressure at once. It also tells the adrenal gland to release aldosterone, which tells the distal tubule and collecting duct to take back more sodium, with water following, while getting rid of potassium. That boost is slower but it lasts.

Every control needs an opposite. When blood volume gets too high the walls of the heart's atria are stretched and release atrial natriuretic peptide, which does the reverse: it makes you lose sodium and water in the urine, lowering blood volume and pressure. So ADH tunes water, the RAAS raises pressure, and ANP lowers it.

Once urine leaves the kidney it is finished, and the rest is moving and storing. The ureters squeeze it down to the bladder by peristalsis, so urine keeps moving even when you lie down. The urinary bladder is a stretchy muscular bag lined with transitional epithelium, which flattens as it fills, and when empty the lining falls into folds called rugae. The muscle in its wall is the detrusor muscle, and a smooth triangle on its floor, the trigone, funnels urine to the exit. Two gates guard the way out. The internal urethral sphincter is smooth muscle and works on its own. The external urethral sphincter is skeletal muscle you control on purpose. The urethra is short in females, about 4 cm, and longer in males, about 20 cm.

Emptying starts as a simple spinal reflex. The bladder fills to about 200 to 400 mL, and stretch receptors in the detrusor wall fire, sending signals to the sacral part of the spinal cord. The cord answers with a parasympathetic command that does two things at once: it contracts the detrusor and relaxes the internal sphincter. That is the micturition reflex. A baby's nervous system has not learned control, so the reflex simply runs to the end. The second gate is what makes you different. Higher brain centers, a control area in the pons guided by the cortex, can hold the external sphincter shut so the urge passes, or relax it when you decide it is time. Losing that override causes many kinds of incontinence.

Worth memorizing

How to reason through the question types

The traps people fall into

Chapter 26Fluid, Electrolyte & Acid-Base Balance

What to know

In a healthy adult about 60 percent of body mass is water, roughly 42 liters in a 70-kilogram person. The share is higher in babies, near 75 percent, and lower in older adults. Fat tissue holds very little water, so a leaner body is a wetter body. Total body water is not one puddle. It is split into compartments kept apart by living membranes.

The biggest split is made by the cell membrane. About two-thirds of your water is inside your cells, the intracellular fluid. The other one-third is outside, the extracellular fluid. Blood vessel walls split the ECF again. Most of it bathes the tissues directly as interstitial fluid, the water in the gaps between cells. A smaller share is the plasma inside the vessels. A tiny extra part is the transcellular fluid, which includes the fluid around the brain and spinal cord, joint fluid and the fluid in the front of the eye.

What makes the compartments different is not the water but the solutes. The ECF is a salty sea much like seawater, full of sodium and chloride. The ICF is rich in potassium, magnesium, phosphate and negatively charged proteins. Every cell membrane runs a sodium-potassium pump around the clock to keep that difference, pushing sodium out and pulling potassium in. The stored difference works like a charged battery, powering nerve signals, muscle squeezing and much of the traffic across membranes.

Water follows dissolved particles by osmosis, so the particle count in each compartment decides where water goes. That count is osmolarity. Add salt to the ECF and it pulls water out of the cells, which shrink. Make the ECF more watery and water rushes in, and the cells swell. Sodium is the most common particle in the ECF, which is why it is the single biggest lever on fluid movement in the body.

Total body water holds steady because of simple bookkeeping: over any 24 hours, water in must equal water out, about 2.5 liters each way. On the way in, most comes from what you drink, about 1.5 L. A good amount is water hidden in food, about 0.7 L. A small real amount is metabolic water, about 0.3 L, made as a by-product each time a cell burns sugar or fat.

Water leaves four ways, and only one is closely controlled. Urine is the largest and the only tightly controlled route, about 1.5 L. Much of the rest is insensible loss, water you lose without noticing as it dries off your skin and leaves as vapor in every breath, about 0.9 L together. A small amount leaves in the feces, about 0.1 L, and more pours out as sweat when you are hot or working hard. Fever, heat, exercise, throwing up and diarrhea can all make these losses soar, which is why they upset the balance so fast.

You choose when to drink, but much of the loss cannot be stopped, so the body controls both ends. When you lose water the ECF gets more concentrated and its osmolarity rises. Tiny sensors in the hypothalamus called osmoreceptors notice and do two things. They cause thirst, which raises intake. And they signal the back of the pituitary to release ADH, which tells the collecting ducts to put in aquaporins so water flows back into the blood. Drink too much and the reverse happens: osmolarity falls, ADH switches off, and a large volume of watery urine flows. Thirst pulls water in and ADH holds water back, and together they keep total body water within about one percent from day to day.

An electrolyte is any substance that breaks into charged ions when it dissolves, letting a fluid carry current. Their uneven spread drives every nerve impulse, every muscle contraction and every shift of water between compartments. They are measured in milliequivalents per liter, a unit that counts electric charge rather than plain weight. Positive ions are cations and negative ions are anions.

Sodium is the main cation of the ECF and the boss of fluid volume, because where sodium goes water follows. Its normal level is 135 to 145 mEq/L, and it is guarded mainly by aldosterone. Potassium is the main cation of the ICF and sets the resting membrane potential, the small charge across nerve and muscle membranes at rest. Its range is narrow, 3.5 to 5.0 mEq/L, and that matters most to the heart: too much or too little can stop it. Calcium is 99 percent stored in bone and runs muscle contraction, blood clotting and nerve signals, tuned by parathyroid hormone and vitamin D. Magnesium is the quieter partner, helping hundreds of enzymes work and keeping nerves and muscles steady.

Because these ions carry charge, small changes cause big symptoms. Low sodium is hyponatremia; it draws water into brain cells and brings confusion, headache and seizures, while high sodium dries brain cells out. Potassium problems are dangerous mainly for the heart: both hyperkalemia and hypokalemia cause arrhythmias that can kill. Low calcium makes nerves too jumpy, which leads to tetany, meaning muscle spasms and tingling, while high calcium dulls nerves and causes weakness and confusion.

pH measures how acidic or basic a fluid is on a scale of 0 to 14, where 7 is neutral. Lower means more acidic, which means more free hydrogen ions. Arterial blood is held slightly basic, in the tiny band of 7.35 to 7.45. That is not a comfort zone but a survival zone. Below 7.35 is acidemia and above 7.45 is alkalemia, and life is not possible outside about 6.8 to 7.8. The stakes are high because pH bends the shape of proteins, and enzymes are proteins, so a drifting pH slows or stops the chemistry of every cell at once. The trouble is that your body makes acid all the time: burning fuel makes carbon dioxide, which turns into acid in water, and hard work or going without food adds lactic acid and ketoacids on top.

The first defense is a buffer, a pair of chemicals that soaks up extra hydrogen ions when acid is added and gives them off when base is added, softening the swing like a sponge. Buffers act in an instant, but they do not remove acid from the body. They only hold it until the lungs or kidneys can clear it. The body's most important buffer is the bicarbonate system, summed up in one reaction worth learning by heart:

CO₂ + H₂O ↔ H₂CO₃ ↔ H⁺ + HCO₃⁻

Read it both ways. When acid floods in, bicarbonate grabs the extra hydrogen ion, driving the reaction left toward carbonic acid and carbon dioxide, which the lungs can breathe out. When base is added, carbonic acid gives up a hydrogen ion to replace what was lost, driving the reaction right. What makes this buffer so strong is that it is open at both ends: the lungs control the carbon dioxide on the left and the kidneys control the bicarbonate on the right, so the body can shift the whole equation instead of using the buffer up. Phosphate buffers back it up inside cells and in the urine, and protein buffers have the biggest total capacity, with hemoglobin buffering the carbon dioxide carried in blood.

The body guards pH in three lines, each on its own clock. Chemical buffering acts within seconds but can only handle so much, and it hides the acid rather than removing it. Respiratory control works in minutes: when blood gets too acidic, sensors notice the rising hydrogen ions and tell the breathing center to breathe faster and deeper, which blows off carbon dioxide and pulls the buffer equation left, so pH climbs. When blood gets too basic, breathing slows and carbon dioxide is kept. This response is quick and very strong, but it cannot fix a problem the lungs caused. Renal control takes hours to days: the kidney can actually add or remove acid and base, secreting hydrogen ions into the urine and taking back or making bicarbonate. It is the slowest line and the only one that can fix an imbalance for good. Buffers buy time, the lungs buy more time, and the kidneys settle the bill.

When pH control fails the result is always one of four disorders, and two questions name any of them. First, which way did pH go? Down below 7.35 is acidosis; up above 7.45 is alkalosis. Second, what is the cause? A lung problem that changes carbon dioxide is respiratory; a problem that changes bicarbonate or other acids is metabolic. Put the two together and you get a two-by-two grid with one disorder in each box.

When one system fails the other steps in, which is compensation. If the trouble is metabolic, the lungs respond within minutes. In diabetic ketoacidosis, for instance, deep fast Kussmaul breathing shows up as the lungs work to blow off carbon dioxide and fight the acid. If the trouble is respiratory, the kidneys respond over days, keeping or dumping bicarbonate. Compensation can be partial, with pH still off, or nearly full, with pH back in range but the other numbers still abnormal. It never overcorrects past normal, and it never cures the cause.

To read a blood gas result, look at three values in order. First the pH: which way is it off? Then the carbon dioxide, the lung number. Then the bicarbonate, the metabolic number. Ask which of the two fits the pH. Low pH with high carbon dioxide means the lungs are to blame, so respiratory acidosis. Low pH with low bicarbonate means metabolism is to blame, so metabolic acidosis. The memory word is ROME: in respiratory problems pH and carbon dioxide move in opposite ways, and in metabolic problems pH and bicarbonate move in the same, or equal, direction.

Worth memorizing

How to reason through the question types

The traps people fall into

Chapter 27The Reproductive System

What to know

Every other system in the book keeps you alive. This one looks past you. Its job is to make a new person, and to do that the body builds a gamete, a sex cell carrying exactly half your genetic instructions, so that when sperm meets egg the full set comes back together.

The male system makes sperm and delivers them in a fluid that feeds them. Sperm are made in the two testes, which hang outside the body wall in a skin sac called the scrotum. That is no accident: sperm making needs a temperature a few degrees cooler than the body core, and a small muscle raises and lowers the testes to hold the right heat, so the scrotum works like a thermostat. Inside each testis are tightly coiled seminiferous tubules, and sperm are made along their walls.

New sperm cannot swim or fertilize. They first move into the epididymis, a comma-shaped coil about 6 meters long lying over the back of each testis, where they spend about two weeks growing up, learning to swim and being stored. Next they enter the ductus deferens, also called the vas deferens, a muscular tube that climbs out of the scrotum and loops over the bladder. It joins the duct of a seminal vesicle to form the short ejaculatory duct, which passes through the prostate and empties into the urethra. In males the urethra is shared plumbing, carrying both urine and semen, though never at the same time.

Sperm are only a small part of semen. Most of it comes from three kinds of helper gland. The two seminal vesicles add the most, a thick fluid full of the sugar fructose that fuels the sperm's tails. The single prostate gland wraps the urethra just below the bladder and adds a milky, slightly alkaline fluid that helps sperm survive the acid in the female body. The small bulbourethral glands give off a clear fluid first, making the urethra slippery and cancelling any acid left from urine.

Spermatogenesis is an assembly line that turns a diploid stem cell into grown-up sperm, running all the time along the tubule walls from puberty on. It starts with a spermatogonium, a stem cell with the full 46 chromosomes, which is diploid or 2n. When it divides, one daughter stays behind as a stem cell, which is why a male never runs out. The other becomes a primary spermatocyte and enters meiosis.

The math is neat. The primary spermatocyte finishes meiosis I and becomes two secondary spermatocytes, each now haploid at n = 23. Each finishes meiosis II, giving four spermatids in all. In sperm making the divisions are equal: every cell gets a fair share of cytoplasm, so one starting cell makes four useful cells. Spermatids are round and cannot move, so a last step called spermiogenesis remodels them. The cell sheds extra cytoplasm, packs its DNA into a small head, puts a cap full of enzymes called the acrosome on that head, and grows a whip-like tail, the flagellum. A middle piece packed with mitochondria gives energy for the trip.

The growing sperm do not look after themselves. Tall sustentacular or Sertoli cells sit among them as nurse cells. They feed the growing sperm and form the blood–testis barrier, a wall that keeps the immune system from attacking sperm as if they were germs. Between the tubules sit the interstitial or Leydig cells, which make testosterone. That hormone drives sperm making and causes male traits such as a deep voice and facial hair. The whole process takes about 64 to 74 days, and a healthy male makes hundreds of millions of sperm every day.

The female system makes the egg and also gives a place where a fertilized egg can attach and grow. The two ovaries, each about the size of an almond, sit low in the pelvis and hold the whole lifetime supply of eggs. About once a month an ovary lets go of a ripe egg, which is ovulation. A uterine tube, also called a fallopian tube, reaches toward each ovary, and its end has a fringe of finger-like fimbriae that sweep the released egg into the tube. Fertilization, if it happens, is usually here, in the outer third of the tube.

The tube carries the egg toward the uterus, a muscular pear-shaped organ with three wall layers worth knowing. The inner endometrium thickens each month to receive an embryo and is shed as the monthly period if none arrives. The thick middle myometrium is smooth muscle that squeezes hard during labor. The thin outer perimetrium is a smooth moist covering. The lower neck of the uterus is the cervix, which opens into the vagina, the muscular birth canal that also receives sperm.

The ovary is also an endocrine organ. Each month a cluster of cells forms around the ripening egg, the follicle, and it pumps out estrogen. After ovulation the leftover follicle turns into the corpus luteum, which makes progesterone. Those two hormones drive the changes in the uterine lining. So the ovary has two jobs: release the egg, and control the tissue that will receive it.

Oogenesis uses the same meiosis as sperm making, but on a very different schedule with a very different goal. The male makes four small sperm from one cell without end. The female makes one large egg from one cell, on a strict once-a-month timetable. The reason is supplies: an egg must carry enough cytoplasm, food and cell parts to start a new life, so the female body pours almost everything into a single egg.

Here is the twist. When a primary oocyte finishes meiosis I, it divides unequally. One daughter, the secondary oocyte, keeps nearly all the cytoplasm. The other becomes a tiny polar body that gets almost nothing and later breaks down. The same lopsided split happens again in meiosis II, and in humans that second division only finishes if a sperm fertilizes the egg. In the end you get one working egg, called an ovum, plus two or three polar bodies that die off. One cell in, one useful egg out, the mirror image of the male's one in, four out.

Oogenesis has the strangest timeline in the body. A female is born with all the eggs she will ever have, about one to two million primary oocytes. Before birth they start meiosis I, then stop partway through and stay frozen for years. Starting at puberty, one oocyte finishes meiosis I each month and is released while the rest keep waiting. So an egg released at age forty has been paused for four decades, which helps explain why chromosome errors become more common as the mother gets older. The supply shrinks over the years, and by menopause only about a thousand follicles are left, too few and responding too weakly to keep the hormone cycle going, so the monthly cycles stop.

The menstrual cycle lasts about 28 days and is really two cycles running in step, one in the ovary and one in the uterus. Four hormones run it. FSH and LH come from the pituitary gland. Estrogen and progesterone come from the ovary. The ovarian cycle tracks the egg and its follicle; the uterine cycle tracks the building and shedding of the lining. The two are timed so a fresh lining is ready just when an egg might arrive.

The cycle starts on day 1 with menstruation, when last month's lining is shed. Next is the follicular phase: FSH gets several follicles to grow, one takes the lead and pours out estrogen, and estrogen rebuilds the lining. Rising estrogen then sets off a sudden jump in LH around day 14. That LH surge causes ovulation, as the lead follicle bursts and lets go of its egg. Then comes the luteal phase: the empty follicle becomes the corpus luteum and makes progesterone, which keeps the lining thick and rich in case an embryo arrives. With no pregnancy the corpus luteum shrinks away, progesterone and estrogen drop, and with no hormones to hold it up the lining is shed.

Here is a neat trick of this cycle. The same hormone can push in opposite ways depending on timing. For most of the cycle estrogen gives negative feedback, quietly holding the pituitary back like a brake. But as the lead follicle ripens, estrogen climbs high and stays high, and at that point the feedback flips to positive. Now high estrogen pushes the pituitary to release the LH surge. This is one of the few places the body uses positive feedback, and as always it is used to cause one big one-time event. After ovulation, progesterone brings negative feedback back and things calm down.

Last, the engine. Every body cell is diploid, with 46 chromosomes in 23 pairs, one of each pair from each parent. If a sperm with 46 joined an egg with 46, the child would have 92 and the number would double every generation. Meiosis is the answer: it makes haploid gametes with 23 chromosomes each, so a haploid sperm and a haploid egg restore the full 46. Cutting the number in half is not a side effect of making gametes; it is the reason meiosis exists.

Meiosis reaches the haploid number in two divisions in a row, with the DNA copied only once, before the first. In meiosis I, matching chromosomes line up as homologous pairs and the pairs are pulled apart, and this is the step that cuts the number in half. Meiosis II looks much like ordinary mitosis: the two copies of each chromosome finally split. The result is four haploid cells, meaning four sperm or one egg plus polar bodies. Compare mitosis, the normal division that builds and repairs the body: one division, two identical diploid cells.

Meiosis also reshuffles your genes so that no two gametes are alike, and it does this two ways. In crossing over, paired chromosomes swap matching pieces during meiosis I, mixing the versions you got from each parent. In independent assortment, each pair lines up and splits at random, so which grandparent's chromosome ends up in a gamete is a coin flip, and that flip happens 23 times over. Together these make millions of different gametes from one person. Sometimes a pair fails to split apart, which is nondisjunction, and the gamete ends up with the wrong number of chromosomes, causing conditions such as trisomy 21.

Worth memorizing

How to reason through the question types

The traps people fall into

Chapter 28Development & Inheritance

What to know

Fertilization is the joining of a sperm and an oocyte into a new cell with its own set of genes. It usually happens high up in the uterine tube, in a wide part called the ampulla, within about a day of ovulation. The released egg can only be fertilized for about 12 to 24 hours, and sperm live a few days at most.

Hundreds of millions of sperm are released, but the trip is harsh. Most are lost to the acid in the vagina or the mucus of the cervix, and many take wrong turns, so only a few hundred reach the egg. On the way the survivors go through capacitation, a last chemical change in the female tract that readies their outer covers to join with the egg.

The egg is not bare. It is wrapped in a halo of follicle cells called the corona radiata, and under that a thick shell of sugar-coated protein called the zona pellucida. To reach the egg's surface a sperm must get through both. A cap over the sperm's head, the acrosome, is a sac full of digesting enzymes. When the sperm touches the zona pellucida the acrosome bursts and spills them, which is the acrosome reaction, and the enzymes dig a narrow tunnel through the shell. It takes many sperm chipping away to get through, so fertilization is a team effort with only one winner. The first sperm to reach the egg's surface grabs receptors there, the two outer covers join, and the sperm's nucleus with its 23 chromosomes slides in.

What if two sperm got in? That is polyspermy, and the embryo would have the wrong number of chromosomes and die. So the egg has two safety locks that snap shut the moment one sperm joins. The fast block comes first: the electric charge across the egg's surface changes right away, which stops other sperm from grabbing on. The slow block, or cortical reaction, comes seconds later: tiny sacs just under the surface spill their contents into the zona pellucida and harden it into a wall no sperm can cross.

Only now does the egg finish its own meiosis II. The two sets of 23 chromosomes come together, bringing back the full count of 46, and the fertilized egg is a single diploid cell called the zygote. Its sex was set at that exact moment, by whether the winning sperm carried an X or a Y chromosome.

Within about a day the zygote starts dividing again and again by mitosis, and those fast divisions are cleavage. Here is the surprise: the whole ball does not get bigger. Each division splits the same cytoplasm into smaller cells, so the cluster stays about the size of the first egg while the cell count climbs 2, 4, 8, 16. Those early cells are blastomeres. All of this happens while the tiny embryo drifts down the uterine tube, pushed by cilia and waves of muscle. By about day 4 it is a solid ball of about 16 cells that looks like a mulberry, so it is called the morula.

Around day 5 fluid seeps into the center and hollows the ball into a fluid-filled sphere, the blastocyst. This is the first time the embryo's cells take on different jobs, and they split into two groups. The outer shell is the trophoblast, which will become the embryo's part of the placenta and the membranes around the baby; it is support tissue, not the baby. Pressed against one inner wall is the inner cell mass, which will become the embryo itself. The fluid space between them is the blastocoel. In a few days the embryo has answered its first big question: which cells build the child, and which build its life-support system.

Implantation is when the embryo digs into the wall of the uterus. First the blastocyst must hatch, breaking free of the leftover zona pellucida so its sticky trophoblast can touch the lining. Around day 6 or 7 the trophoblast sticks to the endometrium and starts to burrow in, its cells releasing enzymes that eat into the lining, and by about day 10 the embryo is fully buried. Right away the trophoblast starts making human chorionic gonadotropin, the hormone that tells the corpus luteum to keep making progesterone so the lining is not shed. That one hormone keeps the pregnancy from ending in a normal period, and it is exactly what a pregnancy test looks for.

Around the third week the inner cell mass makes one of the most important moves in all of growth, gastrulation. A groove called the primitive streak forms down the middle of the flat embryo. Cells from the top layer stream toward it, dive under, and rearrange into three primary germ layers. Your body has more than 200 kinds of cells, and every one comes from one of those three sheets.

The three layers split up the whole body. The outer ectoderm becomes the parts that face the world and sense it: the epidermis and the whole nervous system. The middle mesoderm becomes the bulk and machinery: muscle, bone, blood, heart, blood vessels and kidneys. The inner endoderm becomes the linings of the body's hollow tubes and the glands that grow off them: the lining of the gut and airways, plus the liver and pancreas. An easy way to hold it is that ectoderm is the outside and the wiring, endoderm is the innermost linings, and mesoderm is everything in the middle.

With the layers in place, organogenesis begins, and it runs through the eighth week. The flat disc folds into a shape like a tube inside a tube, and each layer starts shaping its own parts. One of the first and most important steps is ectoderm folding into the neural tube, which becomes the brain and spinal cord. If it does not close all the way the result is a neural tube defect such as spina bifida. The tube closes very early, often before a person knows they are pregnant, so getting enough folic acid around the time of conception greatly lowers the risk.

Growth before birth splits into two named periods at the end of week 8. From fertilization through week 8 is the embryonic period, when the germ layers form and every major organ is first laid down. From week 9 until birth is the fetal period, which is mostly growing and finishing organs that already exist. That split matters for health. A teratogen is a drug, infection or other thing that disrupts growth before birth, and it does its worst harm to body shape in weeks 3 to 8, while parts are forming. The same exposure in the fetal period may cause little or no damage to shape.

A full-term pregnancy lasts about 38 weeks counted from fertilization, or about 40 weeks counted from the last menstrual period, which is how doctors usually count. It splits into three roughly equal trimesters. The first holds all the action: implantation, gastrulation and organ building, and the embryo becomes a fetus at week 9; by the end the fetus looks clearly human but is only about the size of a plum. The second is fast growth and movement, with the first kicks felt, and the fetus nears viability, the point where it could live outside the uterus, about 23 to 24 weeks counted from the last menstrual period or about 21 to 22 weeks after fertilization. The third is mostly weight gain and final growth, with the lungs and brain maturing most of all.

The placenta is a short-term organ built together from the embryo's tissue, which comes from the trophoblast, and the mother's endometrium. Finger-like chorionic villi reach from the baby's side into pools of the mother's blood, making a huge surface for trading. Across that thin barrier oxygen and food pass from mother to fetus while carbon dioxide and wastes pass the other way, yet the two bloodstreams normally never mix. The placenta also becomes a strong hormone maker, taking over from the corpus luteum and making the progesterone and estrogen that keep the pregnancy going. The fetus is tied to it by the umbilical cord and floats inside the amnion, a sac of fluid that cushions it.

Carrying a fetus changes almost every system in the mother's body. Her blood volume rises by about 30 to 50 percent to supply the placenta, and her heart pumps more blood each minute. The growing uterus crowds the diaphragm and bladder, which changes her breathing and makes her need to pee more often. Hormones loosen ligaments, including those of the pelvis, and shift her metabolism to put the fetus's fuel first. These normal changes also explain why pregnancy puts stress on problems like heart disease, and why blood pressure and blood sugar are watched so closely.

Near the end of pregnancy a shift in hormones starts labor, and once it begins a classic positive feedback loop drives it. The baby's head pushes on the cervix, which causes the release of oxytocin. Oxytocin makes the uterus squeeze harder, which pushes the head harder against the cervix, and the loop repeats. It only ends when the baby is born. Labor runs in three stages: dilation, the longest, where squeezes thin and open the cervix all the way to about 10 cm; expulsion, where strong squeezes and the mother's pushing move the baby out; and placental, where the uterus squeezes out the placenta and then clamps down to limit bleeding.

You get one set of chromosomes from each parent, so you carry two copies of nearly every gene. The different versions of a gene are alleles. A person with two matching alleles is homozygous; with two different ones, heterozygous. The pair of alleles a person carries is their genotype, and the trait you can see is their phenotype. All of inheritance is about the link between the two.

When the two alleles differ they do not always count the same. A dominant allele hides the effect of a recessive one, so one copy is enough to show its trait. A recessive allele shows its trait only when both copies are recessive. By custom the dominant allele gets a capital letter and the recessive one a small letter. With B for brown eyes and b for blue, both BB and Bb give brown eyes and only bb gives blue. That is why a recessive trait can seem to skip generations: people with one copy, called carriers, pass it on quietly for years, and it shows up only when two carriers each pass the recessive allele to the same child.

A Punnett square is a simple grid that predicts the chance of each genotype in the children. List one parent's possible alleles across the top, the other parent's down the side, and fill each box by combining them. Cross two brown-eyed carriers, Bb × Bb, and the four boxes come out 1 BB : 2 Bb : 1 bb, a 3 to 1 ratio of brown to blue. So each child has a 25 percent chance of blue eyes even though both parents have brown. Read these as chances, not promises: a one-in-four chance starts fresh with every pregnancy, like a coin flip, so four children could all have brown eyes or two could have blue. Not every trait is this neat. Some alleles are codominant, meaning both show, as in type AB blood, and genes on the X chromosome make special sex-linked patterns. But the two-allele Punnett square is the base everything else builds on.

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