Final Exam Study Guide

The final covers all 28 chapters. Taking them one at a time would mean 28 piles of notes. So this guide groups them into eight themes instead. Each theme pulls together the chapters that share a way of thinking. The first two themes build the vocabulary and the building blocks. The next two cover the frame that moves you and the wires that run it. Then come the two control systems, the two delivery systems, and the systems that trade with the outside world. The last theme looks past you, to the next person. Work one theme a day and all 28 chapters fit into a bit over a week.

Theme 1 · Chapters 1 and 2The language and chemistry of the body

What to know

Two questions run through this whole book. Anatomy asks what a part is and where it sits. Physiology asks what it does and how. The link between them is one rule: structure always fits function.

The body is built in six nested levels. Atoms join into molecules at the chemical level. Molecules build the cellular level, the smallest living unit. Like cells group into a tissue. Two or more tissues build an organ. Organs team up as an organ system. All the systems together are the organism. The cell is the line between chemistry and life.

There are eleven organ systems. They share the work and team up all the time. One breath uses five or more at once. Some organs serve two systems. The pancreas is both digestive and endocrine.

Homeostasis means keeping the inside of the body steady, near a set point. Losing it is the root of most disease. Most control runs on a negative feedback loop with three parts: a receptor senses, a control center compares the reading to the set point, and an effector acts. The response works against the change. That brings the value back.

Positive feedback is the rare opposite. It makes a change bigger and keeps it going until an event is done. There are only a few, and they are worth knowing by name: childbirth, blood clotting and milk release.

All direction words start from the anatomical position: upright, facing forward, palms forward. Right and left always mean the patient's right and left. The words come in pairs, and you use them to compare two parts. Three planes slice the body. Sagittal gives left and right. Frontal, also called coronal, gives front and back. Transverse gives top and bottom. A midsagittal cut makes two mirror halves.

Organs sit in cavities. The dorsal cavity holds the brain and spinal cord. The diaphragm splits the ventral cavity into the thoracic and abdominopelvic cavities. Serous membranes line them and give off fluid so organs do not rub. The three are the pleura around the lungs, the pericardium around the heart, and the peritoneum in the belly. The belly is mapped into four quadrants or nine regions.

Now the chemistry. All matter is made of elements. The smallest unit of an element is the atom. It has a nucleus of protons and neutrons, with electrons in shells around it. The atomic number is the proton count, and it names the element. Isotopes are the same element with a different neutron count. Six elements make up about 99 percent of the body: O, C, H, N, Ca and P.

Atoms bond to fill their outer, or valence, shell. A full shell is stable. That is the octet rule. There are three bonds to know. An ionic bond passes an electron from one atom to another. The two charged ions then attract. A covalent bond shares electrons. Equal sharing is nonpolar. Unequal sharing is polar. Covalent bonds are the strongest in the body. A hydrogen bond is a weak pull between polar molecules. One is weak, but millions hold water, DNA and proteins together.

Reactions rearrange atoms three ways. Synthesis builds, so A plus B gives AB. Decomposition breaks apart, so AB gives A plus B. Exchange swaps partners. Every reaction must first climb its activation energy hill. Exergonic reactions give off energy. Endergonic reactions take it in. An enzyme is a protein helper that lowers the hill. It is not used up, and it is very specific to its substrate. Because an enzyme depends on its shape, high heat or the wrong pH can stop it.

Water is polar, and that one fact explains all its tricks. Its molecules hydrogen-bond to each other. It is the body's solvent, pulling apart anything water-loving. It has a high heat capacity, so it holds body temperature near 37 °C. It cools you as it evaporates. It sticks to itself, which gives slippery films. And it is a reactant: taken out in dehydration synthesis, added in hydrolysis.

pH measures free hydrogen ions. Below 7 is acidic and above 7 is basic. The scale is logarithmic, so each unit is a ten-fold change. An acid gives off hydrogen ions and a base takes them up. Blood must stay between 7.35 and 7.45. Below that is acidosis and above it is alkalosis. Buffers, mainly the bicarbonate system, hold the line.

Life is built from four families of organic molecules, all on a carbon backbone. Carbohydrates are quick fuel, built from single sugars. Lipids store energy, build membranes and make hormones. Proteins are the workhorses, built from 20 kinds of amino acid, and shape sets the job. Nucleic acids, DNA and RNA, store and use genetic information. Big molecules are polymers of repeating monomers. They are built by dehydration synthesis and broken by hydrolysis. ATP is the energy currency. It gives off energy when its last phosphate comes off.

Worth memorizing

How to reason through the question types

The traps people fall into

Theme 2 · Chapters 3 and 4Cells and tissues

What to know

Every cell is wrapped in a plasma membrane. It does three things: it separates, it controls traffic, and it communicates. The fluid mosaic model describes it as a fluid phospholipid bilayer with proteins, cholesterol and sugars set into it like tiles. The water-loving heads face out and the water-fearing tails face in.

Small fat-soluble molecules cross that oily middle easily. Ions and other water-loving molecules need protein channels or carriers. Water seeps through slowly on its own, and much faster through aquaporin channels. Cholesterol keeps the membrane from getting too stiff or too runny. The sugary glycocalyx lets cells know each other and marks self.

Only one question sorts all the transport: does it cost energy? Passive transport moves things down their gradient for free. Simple diffusion goes right through the fat layer, as oxygen and carbon dioxide do. Facilitated diffusion goes downhill through a protein. Osmosis moves water toward the saltier side. Active transport pushes uphill and costs energy. The sodium-potassium pump is the classic. For each ATP it pushes 3 sodium out and brings 2 potassium in. That one pump powers the electrical signals of nerves and muscles. Bulk transport moves the biggest cargo wrapped in membrane: endocytosis in, exocytosis out.

Inside, organelles are departments floating in the cytosol, and their membranes keep their jobs apart. The nucleus stores DNA as chromatin, which packs into chromosomes before division. The nucleolus builds ribosomes. The protein path runs ribosomes, then rough ER, then Golgi, then vesicles. The smooth ER makes fats, breaks down harmful substances and stores calcium. Mitochondria make ATP. Lysosomes break down junk. The cytoskeleton gives shape and moves cargo.

A gene is the recipe for one protein, and the flow is DNA to RNA to protein. Transcription happens in the nucleus, where RNA polymerase copies a gene into mRNA. RNA uses uracil in place of thymine. The copy leaves through a nuclear pore. Translation happens at a ribosome, which reads the mRNA in three-base codons. tRNA anticodons bring the matching amino acids, which link into a chain that folds into a working protein. Change one base and you can change one amino acid and break the protein, as in sickle cell disease.

The cell cycle is a long interphase plus a short mitosis. Interphase runs G₁ for growth and normal work, S where all the DNA is copied, and G₂ for last growth and checking. Mitosis runs in the order PMAT: prophase packs chromatin into chromosomes and forms the spindle, metaphase lines them up across the middle, anaphase pulls the copies to opposite ends, and telophase forms two new nuclei. Then cytokinesis splits the rest of the cell. The result is two genetically identical daughter cells. Checkpoints, guarded by genes such as p53, stop damaged cells from dividing. When they fail, cancer can follow.

Osmosis moves water toward the side with more solute. Tonicity says what that does to a cell. In an isotonic fluid there is no overall change. In a hypotonic fluid water goes in and the cell swells or bursts, which is lysis. In a hypertonic fluid water goes out and the cell shrivels, which is crenation. Always find the saltier side. This is why IV fluids are chosen with care, and why 0.9 percent normal saline is isotonic.

A tissue is a group of similar cells doing a shared job, and the study of them is histology. The whole body is built from four. Epithelial tissue covers surfaces, lines spaces and forms glands. Connective tissue binds, supports, protects, stores and carries. Muscle tissue contracts to make movement, force and heat. Nervous tissue senses, sorts and quickly sends electrical signals. A quick way to tell the first two apart: epithelial cells are tightly packed, while connective cells are spread out in a matrix.

Every epithelium is polar, with an apical top and a basal bottom. It sits on a basement membrane, has no blood vessels of its own, and regenerates fast. You name it with two words: layers plus cell shape. Simple means one layer and stratified means many. Squamous is flat, cuboidal is cube, columnar is tall. Simple types are for absorbing, releasing and diffusion. Stratified types are for protection. Pseudostratified and transitional are the special cases.

All connective tissue follows one recipe: spread-out cells in an extracellular matrix of fibers plus ground substance. There are three fiber types. Collagen gives strength, elastic fibers give stretch, and reticular fibers give mesh support. Cells ending in -blast build the matrix, and cells ending in -cyte keep it up. Change the matrix and you get the whole family: loose, adipose, dense, cartilage, bone and blood.

Muscle contracts as actin and myosin threads slide. Neat rows of threads make the tissue look striated. Three questions tell the three types apart: striped, voluntary, and what shape are the cells. Skeletal is striated and voluntary, with long fibers that have many nuclei. Cardiac is striated and involuntary, with short branched cells joined by intercalated discs. Smooth is not striated and is involuntary, with tapered spindle cells.

The neuron is shaped like a message. Dendrites receive, the cell body adds up the input, and one long axon sends the pulse on. A fatty myelin sheath speeds the signal. Axon terminals pass it to the next cell at a synapse. Neuroglia support and protect neurons. Nervous tissue is defined by excitability and conductivity, and grown-up neurons rarely divide, which is why brain and cord damage often heals poorly.

Hurt tissue heals two ways. Regeneration brings back the same cells and normal function. Fibrosis fills the gap with scar, which brings back strength but not full function. Which one you get depends mostly on blood supply and how easily the cells divide. The steps always run in order: hemostasis, then inflammation, then proliferation, then remodeling. Inflammation is the repair at work, not the injury.

Worth memorizing

How to reason through the question types

The traps people fall into

Theme 3 · Chapters 5 to 11Support and movement

What to know

The integumentary system is the skin plus hair, nails and glands, and the skin is the body's largest organ. It has two true layers. The epidermis is keratinized stratified squamous epithelium and has no blood vessels. It sits on the dermis, dense irregular connective tissue that holds the vessels, nerves, follicles and glands. Below both is the hypodermis of fat and loose tissue, which is not skin. Thick skin on palms and soles has five epidermal layers. Thin skin has four and grows hair.

Keratinocytes are born in the deepest layer, pushed upward and shed in about a month. That is keratinization. The five strata from deep to surface are basale, spinosum, granulosum, lucidum and corneum. The lucidum is found only in thick skin. The corneum is the dead, keratin-filled barrier you touch.

Skin color mixes three pigments: melanin, which is the main one, plus carotene and hemoglobin from blood. Melanocytes in the stratum basale make melanin and hand it to keratinocytes, where it caps the nucleus and soaks up ultraviolet light to protect DNA. Everyone has about the same number of melanocytes. Color differs by the amount and type of melanin. Color also gives clues about the blood: cyanosis is low oxygen, pallor is low flow or anemia, erythema is more flow, and jaundice is a bilirubin buildup.

Hair and nails are dead keratin that grow from living matrices. Sebaceous glands make oily sebum. Eccrine sweat glands are all over the body and cool you as sweat evaporates. Apocrine glands in the armpit and groin feed the bacteria that cause body odor.

The skin does five jobs: protection, thermoregulation, sensation, vitamin D synthesis, and excretion and storage. Protection is physical through keratin, chemical through the slightly acidic acid mantle, and biological through immune dendritic cells. To cool, sweat evaporates and dermal vessels widen. To warm, those vessels narrow. Ultraviolet light turns a relative of cholesterol into vitamin D₃, which you need to absorb calcium.

Burns are graded by depth. First-degree hurts the epidermis only: red, dry, painful, no blisters. Second-degree reaches the dermis and blisters. Third-degree goes all the way through, looks leathery, is often painless because the nerves are destroyed, and needs grafting. Serious burns kill through fluid loss and infection, and the rule of nines estimates the area burned. The three skin cancers are basal cell, which is common and mild, squamous cell, which can spread, and melanoma, which is rare but deadly.

Bone is living tissue. The skeleton does five jobs: support, protection, movement, mineral and fat storage, and hematopoiesis. About 99 percent of the body's calcium is stored in bone. The axial skeleton has about 80 bones and the appendicular about 126, for 206 in all. Bones come in five shapes: long levers, short steady supports, flat protectors, irregular specialists, and sesamoid bones inside tendons, the largest being the patella.

A long bone has a diaphysis shaft of compact bone around a marrow-filled medullary cavity. Its epiphyses are spongy bone with red marrow, capped by articular cartilage. The metaphysis holds the epiphyseal plate, which becomes the epiphyseal line when growth stops. The periosteum wraps the outside and the endosteum lines the inside. Compact bone is built of osteons: rings of lamellae around a central canal, with osteocytes in lacunae linked by canaliculi.

Bone matrix is collagen for bending plus hydroxyapatite mineral for hardness, and it needs both. Four cells run it. The osteogenic cell is the source. The osteoblast builds, so b for build. The osteocyte maintains and senses stress. The osteoclast breaks bone down, so c for carve. Remodeling balances the two and replaces about 10 percent of bone a year. It answers load, which is Wolff's law. If breakdown wins for long, the result is osteoporosis.

Blood calcium is held near 9 to 10 mg/dL, because nerves, muscles and clotting all depend on it. Parathyroid hormone raises it by spurring osteoclasts, making the kidney take calcium back, and switching on vitamin D so the gut absorbs more. Calcitonin from thyroid C cells lowers it by holding osteoclasts back. The body will take calcium out of bone to protect the blood level.

Fractures have named patterns: closed or open, plus transverse, oblique, spiral, comminuted, impacted and greenstick. Healing runs in four stages: fracture hematoma, soft callus, hard callus at about six weeks, then remodeling over months. Treatment is reduction then immobilization.

The axial skeleton has three parts. The skull has 22 bones: 8 cranial around the brain and 14 facial. The single cranial bones are the frontal, occipital, sphenoid and ethmoid, and the parietal and temporal come in pairs. The mandible is the only skull bone that moves freely. The others meet at sutures, which in babies are still open as fontanelles.

The vertebral column has 26 bones in five regions, and the counts are worth chanting: 7 cervical, 12 thoracic, 5 lumbar, plus the fused sacrum and coccyx. C1 is the atlas and C2 is the axis. Vertebrae get larger going down because they carry more weight, so the lumbar ones are largest. Intervertebral discs cushion and allow movement. Every vertebra has a weight-bearing body in front and a protective arch behind, surrounding the vertebral foramen that the cord runs through, plus processes for muscles and joints.

The thoracic cage is the three-part sternum, which is manubrium, body and xiphoid process, plus 12 pairs of ribs. Ribs 1 to 7 are true ribs joining the sternum directly. Ribs 8 to 10 are false ribs joining through the rib above. Ribs 11 and 12 are floating ribs with no front attachment. The spine has four curves. The thoracic and sacral are primary and present at birth. The cervical and lumbar are secondary and form as a baby lifts its head and learns to walk. Problem curves are kyphosis, lordosis and the sideways scoliosis.

The appendicular skeleton trades off the other way. The pectoral girdle is just the clavicle and scapula. The arm's only bony link to the axial skeleton is the sternoclavicular joint, and the scapula floats on muscle. The glenoid cavity is shallow, giving up steadiness for range. The clavicle is the most commonly fractured bone. The upper limb has three long bones: the humerus, plus the radius on the thumb side and the ulna on the pinky side. The ulna leads at the elbow through its olecranon, and the radius leads at the wrist and does the turning. The hand has 27 bones: 8 carpals, 5 metacarpals and 14 phalanges.

The pelvic girdle chooses strength. Each hip bone is the ilium, ischium and pubis fused at the acetabulum, and it joins the axial skeleton firmly at the sacroiliac joints. The female pelvis is wider and shallower, with a subpubic angle above 90 degrees, shaped for childbirth. The lower limb holds the strongest bones: the femur, the longest and strongest in the body; the patella, the largest sesamoid; the weight-bearing tibia; and the steadying fibula. The foot has 26 bones: 7 tarsals, 5 metatarsals and 14 phalanges. The talus takes weight from the leg and the calcaneus is the heel.

Every joint is described twice. By structure it is fibrous, cartilaginous or synovial. By function it is a synarthrosis that does not move, an amphiarthrosis that moves a little, or a diarthrosis that moves freely. The two match because the material sets the motion. The theme of the whole chapter is the mobility and stability trade-off: more movement always costs stability.

Synovial joints are the ones that move freely, and all six types share one design. Plane joints are nonaxial and glide. Hinge and pivot are uniaxial. Condyloid and saddle are biaxial. Ball-and-socket is multiaxial and moves the most. The saddle joint at the base of the thumb makes the human grip possible. Inside, the key feature is a fluid-filled joint cavity. Articular cartilage caps the bones, an articular capsule wraps the joint, and synovial fluid does three jobs: it oils, it feeds the cartilage, which has no blood vessels, and it cushions. Bursae pad spots where tendons rub.

Movements come in opposite pairs, all defined from the anatomical position. Flexion and extension change a joint angle. Abduction and adduction move a limb away from or toward the midline. Rotation spins a bone on its axis, and circumduction joins several motions into a cone. Special movements include supination and pronation of the forearm, dorsiflexion and plantar flexion of the foot, inversion and eversion, elevation and depression, and opposition of the thumb.

Four joints show the trade-off in four ways. The shoulder moves the most and dislocates the most, held by the rotator cuff. The hip is a deep socket bound by thick ligaments, built for weight. The knee is a complex hinge held by menisci and cruciate ligaments, which twisting tears. The elbow gives up range to be a snug hinge with a pivot.

Muscle tissue contracts. A skeletal muscle is bundles inside bundles: epimysium wraps the whole muscle, perimysium wraps each fascicle, and endomysium wraps each fiber. All of them join the tendon. Inside a fiber are the sarcolemma, its T-tubules, the sarcoplasmic reticulum, and myofibrils of actin and myosin.

The sarcomere, from Z-disc to Z-disc, is the functional unit. Thick filaments are myosin with heads. Thin filaments are actin, guarded by tropomyosin and by troponin, which senses calcium. Watch the bands to prove sliding: the A band stays the same, while the I band and H zone narrow.

In the sliding filament theory the filaments keep their length. The sarcomere shortens as they overlap more. The cross-bridge cycle has four steps: a charged myosin head binds an open site on actin, the power stroke swivels and slides the thin filament, a new ATP lets the head go, and splitting that ATP re-cocks the head. ATP is needed both to release and to re-charge. In excitation-contraction coupling, an action potential runs down the T-tubules, the sarcoplasmic reticulum releases calcium, and troponin moves tropomyosin off the binding sites. To relax, a pump returns the calcium.

The neuromuscular junction is where a motor neuron signals a fiber. Acetylcholine crosses the synaptic cleft and binds nicotinic receptors on the motor end plate. Sodium floods in, makes an end-plate potential, and sets off a muscle action potential. Then acetylcholinesterase ends the signal. Problems follow the messenger: blocking acetylcholine gives weakness, and letting it last too long gives spasm.

A motor unit is one motor neuron plus all the fibers it controls. Small units give fine control and large units give power. Tension builds from a twitch through wave summation to tetanus as stimuli come faster, and real movement uses tetanus. Force is set two ways: recruitment, adding units smallest first, which is the size principle, and rate coding, firing faster. The steady activity at rest is muscle tone.

Three fiber types trade speed for stamina. Slow oxidative type I is slow, resists fatigue, uses oxygen, and is red with many mitochondria and much myoglobin. Fast glycolytic type IIx is fast and powerful but tires quickly, and is pale. Fast oxidative type IIa sits in between. Most muscles are a mix shaped by genes and training.

A muscle can only pull. So muscles work in opposing pairs across joints, and each pulls its insertion, the moving end, toward its origin, the fixed end. Every move uses four roles: the agonist makes it, the antagonist works against and lengthens, the synergist helps or steadies, and the fixator holds the origin still. Bones act as levers, and most body joints are third-class levers, favoring speed and range over force.

Muscle names are descriptions built from six clues: location, shape, size, fiber direction, number of heads, and action. Decode the name and you can work out a muscle you never memorized.

Worth memorizing

How to reason through the question types

The traps people fall into

Theme 4 · Chapters 12 to 16Control by nerves

What to know

The nervous system splits two ways. By location, the central nervous system is the brain and spinal cord, and the peripheral nervous system is the nerves and ganglia. By job, afferent or sensory signals arrive at the CNS, and efferent or motor signals exit toward effectors. Afferent arrives and efferent exits. Every act comes down to three steps: sensory input, integration, motor output.

The motor side splits again. Somatic is voluntary and goes to skeletal muscle. Autonomic is involuntary and goes to heart muscle, smooth muscle and glands. The autonomic side splits into sympathetic, which is fight or flight, and parasympathetic, which is rest and digest.

A neuron has three parts: dendrites receive, the cell body adds up signals, and the axon sends. Six neuroglia support them. In the CNS, astrocytes are the most common and help form the blood-brain barrier, oligodendrocytes make myelin and each one wraps many axons, microglia are the immune cells, and ependymal cells line the hollow spaces and move cerebrospinal fluid. In the PNS, satellite cells support cell bodies in ganglia and Schwann cells make myelin, one cell per segment.

At rest the membrane is polarized to about −70 mV, with the inside negative. That comes from unequal ions: sodium is high outside, potassium is high inside, and large negative proteins are trapped inside. Potassium leaking out through open channels is the main thing setting the voltage. The sodium-potassium pump keeps the gradients up and makes the inside a little more negative still.

An action potential fires only if the membrane reaches threshold at about −55 mV, and then it is all-or-nothing. In depolarization, voltage-gated sodium channels open, sodium floods in, and the voltage climbs to about +30 mV. In repolarization, the sodium channels inactivate, potassium channels open, potassium leaves, and the voltage falls. A brief hyperpolarization dips to about −80 mV before the leak channels and the pump restore rest. The refractory period keeps the signal moving one way and limits firing rate. Stimulus strength is coded by frequency, not by size.

Continuous conduction rebuilds the spike at every patch, and it is slow. Saltatory conduction leaps between the bare gaps, the nodes of Ranvier, which are packed with sodium channels. Speed rises with myelination and with axon diameter. Diseases that strip myelin slow or block signals.

Neurons meet at a synapse across the synaptic cleft. The sender is presynaptic and the receiver postsynaptic. The sequence is: the action potential arrives, calcium enters, vesicles merge with the membrane, neurotransmitter is released, it binds receptors, then it is cleared. An EPSP pushes the receiving cell toward threshold and an IPSP pushes it away. The cell sums them to decide whether to fire. Key transmitters: acetylcholine at muscle, glutamate as the main excitatory, GABA as the main inhibitory, glycine inhibitory in the cord, norepinephrine for alertness, and dopamine for reward and movement.

The cerebral cortex is a folded sheet of gray matter, and its gyri and sulci fit more surface into the skull. Four lobes are named for the skull bones above them. The frontal lobe handles chosen movement, planning, judgment, personality and speech production in Broca's area. The parietal lobe handles touch, pressure, pain and temperature, plus sense of space. The temporal lobe handles hearing, smell, memory and understanding language in Wernicke's area. The occipital lobe handles vision. The central sulcus splits the motor cortex in front from the somatosensory cortex behind. The corpus callosum links the halves.

Four regions stack from thinking down to survival. The cerebrum thinks, feels, moves and remembers. The diencephalon holds the thalamus, which relays almost all sense signals to the cortex, and the hypothalamus, which keeps the body steady and runs the pituitary. The brainstem is the midbrain, pons and medulla oblongata, and it holds the life-saving reflex centers for heart rate, blood pressure and breathing. The cerebellum smooths movement and keeps balance. It edits motion; it does not start it.

The brain floats. The choroid plexus in the ventricles makes cerebrospinal fluid from filtered plasma. It flows from the two lateral ventricles to the third, down the cerebral aqueduct to the fourth, out into the subarachnoid space, and back into the blood at the arachnoid granulations. CSF gives buoyancy, shock protection and chemical stability. A blocked flow causes hydrocephalus.

Three meninges wrap the brain and cord. From outside in they are the tough dura mater, the web-like arachnoid mater, and the thin pia mater that clings to every fold. The subarachnoid space under the arachnoid holds the flowing CSF. The spaces name the bleeds. An epidural bleed is arterial and lens-shaped. A subdural bleed is venous and crescent-shaped.

The spinal cord runs to about L1 to L2, and below that the nerve roots continue as the cauda equina. 31 pairs of spinal nerves branch off. In a slice, gray matter horns sit in the center with white matter tracts around them, which is the reverse of the brain. The rule to hold is the Bell-Magendie rule: dorsal horns and roots are sensory in, and ventral horns and roots are motor out. The dorsal root ganglion holds the sensory cell bodies.

Twelve pairs of cranial nerves are numbered I to XII from front to back, and all but the first two come from the brainstem. Each is sensory, motor or mixed. Several move the eye, namely III, IV and VI. Three carry special senses: I for smell, II for vision, VIII for hearing and balance. The vagus, number X, is the only one that leaves the head and neck, carrying most parasympathetic signals to the organs.

Sensation begins when a receptor turns a stimulus into a nerve signal, which is transduction. General senses are found all over the body; special senses live in organs of the head. Receptors are named for what they detect: mechanoreceptors for push and bend, thermoreceptors for temperature, nociceptors for damage and pain, chemoreceptors for chemicals, and photoreceptors for light. Most receptors adapt to a steady stimulus. Nociceptors hardly adapt at all.

The eye has three tunics. The fibrous outer tunic is the sclera and the cornea, and the cornea does most of the focusing. The vascular middle tunic is the choroid, ciliary body and iris. The neural inner tunic is the retina. Light travels cornea, aqueous humor, pupil, lens, vitreous, retina. In accommodation, the ciliary muscle tightens and the lens gets rounder for close vision. The fovea is all cones and gives the sharpest sight. The optic disc is the blind spot. Rods work in dim light and cones give color.

The visual pathway runs retina, optic nerve, optic chiasm, optic tract, thalamus, then the visual cortex in the occipital lobe. At the chiasm the nasal fibers cross, so each side of the brain handles the opposite half of what you see. Where the damage is predicts the loss. One optic nerve gives blindness in that eye. The center of the chiasm gives bitemporal hemianopia. Beyond the chiasm on one side gives homonymous hemianopia.

The ear has three parts. The outer ear gathers sound and vibrates the eardrum. The middle ear's three ossicles make the vibration stronger and pass it to the oval window. The inner ear holds the cochlea for hearing and the vestibule and semicircular canals for balance. The organ of Corti sits on the basilar membrane, and its hair cells fire the cochlear nerve. Pitch is mapped by place: the base for high tones and the apex for low. Hair-cell loss is permanent.

Taste and smell are the chemical senses. Taste reads molecules dissolved in liquid; smell reads molecules in the air. Taste buds detect five basic tastes: sweet, sour, salty, bitter and umami. Smell neurons reach the brain through the cribriform plate, and they are among the few nerve cells that regenerate. Smell is the one sense that skips the thalamus. It links straight to the limbic system, which ties it to memory and feeling.

A reflex is a fast response you do not choose, turning around in the cord or brainstem. Every reflex arc has five parts: receptor, sensory neuron, integration center, motor neuron, effector. The stretch reflex, as in the knee-jerk, is monosynaptic. Withdrawal reflexes are polysynaptic and add interneurons. Reciprocal inhibition relaxes the opposite muscle. Testing a reflex checks the whole arc.

The autonomic nervous system runs smooth muscle, heart muscle and glands. Its two divisions pull opposite ways. Sympathetic fibers leave the thoracolumbar cord from T1 to L2. Parasympathetic fibers leave craniosacral points: cranial nerves III, VII, IX and X, plus S2 to S4. Most organs have dual innervation, and the body steers them by shifting the balance of steady autonomic tone, not by switching one on from off.

Every autonomic path uses two neurons that meet at a ganglion. Sympathetic ganglia sit near the cord, so the first fiber is short and the second long, and high divergence gives a body-wide response. Parasympathetic ganglia sit at the organ, so the first fiber is long and the second short, and low divergence gives a local response. The adrenal medulla is a changed sympathetic ganglion that releases epinephrine into the blood as a hormone, which is why the rush fades slowly.

Only two chemicals do all the talking. All preganglionic fibers and all parasympathetic postganglionic fibers release acetylcholine, so they are cholinergic. Most sympathetic postganglionic fibers release norepinephrine, so they are adrenergic. The exception is sympathetic fibers to sweat glands, which use acetylcholine. The receptor decides whether a target speeds up or slows down: nicotinic or muscarinic for acetylcholine, alpha or beta for norepinephrine. That is why autonomic drugs can be so precise.

The baroreceptor reflex is the fastest blood-pressure guard, and it is negative feedback. Baroreceptors in the carotid sinus and aortic arch sense stretch and report through cranial nerves IX and X to the medulla. The medulla then shifts the sympathetic and parasympathetic balance, changing heart rate, heart force and vessel width. A slow reflex causes orthostatic hypotension, that lightheaded moment on standing.

The neurological exam exists to localize a problem at the bedside. Its five parts check the system from top to bottom: mental status for the cortex, cranial nerves for the brainstem, sensory for nerves, cord and pathways, motor for the motor pathway, and coordination and gait for the cerebellum.

Language is usually on the left. Broca's area produces speech, and damage gives slow, hard, choppy speech with understanding intact and the patient frustrated. Wernicke's area understands language, and damage gives smooth but meaningless speech with understanding lost and the patient unaware.

A dermatome is the strip of skin served by one spinal nerve, so numbness in a strip names the level. Landmarks worth holding: C6 thumb, C7 middle finger, C8 little finger, T4 nipple line, T10 umbilicus, L1 groin, S1 sole. Two sensory roads go up. The spinothalamic tract carries pain and temperature and crosses right away in the cord. The dorsal columns carry touch, vibration and position and cross high up in the medulla.

Strength is graded 0 to 5, and grade 3 is the turning point: the limb moves against gravity but not against a push. The motor pathway has two relays, and telling them apart is a classic. An upper motor neuron problem gives higher tone, stiff or spastic weakness, stronger reflexes, a Babinski sign and little late wasting. A lower motor neuron problem gives lower tone, limp or flaccid weakness, weak or missing reflexes, early heavy wasting and visible twitches.

The cerebellum makes movement smooth and accurate. When it fails you get ataxia: dysmetria on finger-to-nose, an intention tremor worse near the target, dysdiadochokinesia on rapid alternating movements, and a wide-based staggering walk. One test is a trap. A positive Romberg, steady with eyes open but falling with eyes closed, is a position-sense and dorsal-column sign, not a cerebellar one.

Worth memorizing

How to reason through the question types

The traps people fall into

Theme 5 · Chapter 17Control by hormones

What to know

Theme 4 was the fast messenger. This is its patient partner. The endocrine system has no wires. Its glands drop hormones into the blood, and the blood carries them everywhere. You trade speed for reach and staying power. A hormone takes seconds to minutes to act, but the effect can be wide and can last a long time.

Endocrine glands are ductless and release straight into the blood. Exocrine glands use a duct to send their product onto a surface, as sweat, spit and tear glands do. The pancreas does both. Its exocrine part drips enzymes into a duct, and its endocrine islands release insulin and glucagon into the blood.

A hormone reaches every cell but only changes the ones with the matching receptor. Those are its target cells. That is how one messenger in the blood can do a narrow job.

Chemistry decides how a hormone talks to a cell. Most are amino-acid based, which includes peptides and proteins such as insulin and growth hormone, and amines such as the adrenal catecholamines. These are water-soluble and cannot cross the fatty membrane. The other family is the steroid hormones, built from cholesterol, which includes cortisol, aldosterone and the sex hormones. These are lipid-soluble and slip right through.

A lipid-soluble hormone walks in and binds an intracellular receptor, usually in the nucleus. The pair works on the DNA and switches genes on or off. The cell then makes new proteins, often new enzymes. Building takes time, so the start is slow, measured in hours, and the effect is long.

A water-soluble hormone binds a surface receptor and starts a relay inside. The relay runs on a second messenger, best known being cyclic AMP. The hormone stays outside as the first messenger. The second messenger switches on a chain of enzymes already waiting in the cell, so the answer is fast, in seconds to minutes, and it fades fast once the hormone is gone. Learn one exception: thyroid hormone is an amine but dissolves in fat, so it enters the cell and acts on genes like a steroid.

The pituitary is pea-sized and hangs just under the brain. People call it the master gland, but it has a boss. The hypothalamus sits above it and turns brain signals into hormone orders, so the hypothalamus is the true master.

The posterior pituitary makes nothing. It is nerve tissue grown down from the hypothalamus. Two hormones made by hypothalamic nerve cells travel down their long arms and wait here: antidiuretic hormone, which tells the kidney to save water, and oxytocin, which squeezes the uterus in childbirth and makes milk flow. It is a release station, not a factory.

The anterior pituitary is real gland tissue and makes six hormones, but only when the hypothalamus says so. The hypothalamus sends releasing and inhibiting hormones down a private set of vessels, the hypophyseal portal system. Four of the six are tropic, meaning their target is another gland: TSH drives the thyroid, ACTH drives the adrenal cortex, and FSH and LH drive the gonads. Growth hormone acts on almost every tissue and prolactin acts on the breast. The memory word is FLAT PIG, with the four tropic ones first.

The pancreatic islets guard blood sugar with an antagonistic pair. Beta cells make insulin and alpha cells make glucagon. After a meal, insulin lowers blood sugar: it tells cells to take sugar in and the liver to store it as glycogen. Between meals, glucagon raises it: it tells the liver to split glycogen back down, which is glycogenolysis, and to build new sugar from other molecules, which is gluconeogenesis. Insulin is the fed-state hormone and glucagon the fasting-state one. Insulin is also the only hormone that lowers blood glucose.

The thyroid wraps the front of the windpipe and makes T₃ and T₄. The numbers count iodine atoms, which is why you need iodine in food. Thyroid hormone sets the basal metabolic rate, the speed at which nearly every cell burns fuel and makes heat. Three steps hold it steady in the hypothalamus-pituitary-thyroid axis, a classic negative feedback loop: the hypothalamus releases TRH, TRH calls out TSH, TSH makes the thyroid release T₃ and T₄, and those hormones loop back and block both earlier steps. In hypothyroidism everything slows and in primary disease TSH rises. In hyperthyroidism everything speeds up and TSH falls.

The adrenal gland caps each kidney and is two glands joined. The outer cortex makes steroids and you cannot live without it. The inner medulla makes epinephrine and norepinephrine and is a direct part of the sympathetic nervous system. The medulla answers in seconds; the cortex takes minutes to hours. The cortex has three zones, and you can read the job off the layout going inward: the zona glomerulosa makes aldosterone for salt, the wide zona fasciculata makes cortisol for sugar and stress, and the zona reticularis makes androgens for sex.

Worth memorizing

How to reason through the question types

The traps people fall into

Theme 6 · Chapters 18 to 21Transport and defense

What to know

Blood is a connective tissue: cells spread through an extracellular matrix. The cells are the formed elements and the matrix is the liquid plasma. An adult holds about 5 liters, about 8 percent of body weight, at about 38 °C, with pH held between 7.35 and 7.45. Its jobs fit three groups: transport, regulation and protection.

Spin a tube and blood splits into three visible layers. Plasma on top is about 55 percent. A thin buffy coat of white cells and platelets is under 1 percent. Packed red cells on the bottom are about 45 percent, and that share is the hematocrit. Normal runs about 37 to 47 percent in women and 42 to 52 percent in men. Plasma is about 92 percent water, and most of the rest is plasma proteins: albumin, which holds water inside the vessels, globulins, which include antibodies, and fibrinogen, the raw material for clots. Serum is plasma with the clotting proteins taken out.

The formed elements are three. Erythrocytes number about 5 million per microliter, platelets a few hundred thousand, and leukocytes only about 5,000 to 10,000. A red cell is a biconcave disc with no nucleus and no organelles, so it cannot repair itself and lasts about 120 days. White cells all keep their nuclei. Granulocytes are neutrophils, eosinophils and basophils. Agranulocytes are lymphocytes and monocytes. From most to least common: neutrophil, lymphocyte, monocyte, eosinophil, basophil. Platelets are fragments pinched off megakaryocytes and live about 10 days.

Hematopoiesis happens in red bone marrow, and every blood cell comes from one multipotent hematopoietic stem cell. Multipotent means any blood cell but only a blood cell. The myeloid line is the broad one and makes red cells, platelets and most white cells. The lymphoid line makes only lymphocytes. Erythropoietin from the kidney drives red cell making when oxygen is low. The raw materials are iron, vitamin B₁₂ and folate.

Hemoglobin has four globin chains, each holding a heme with an iron atom, so it carries four oxygen molecules. In the lungs it binds oxygen as bright oxyhemoglobin; in the tissues it lets go as darker deoxyhemoglobin. Oxygen rides 98.5 percent on hemoglobin and 1.5 percent dissolved. Carbon dioxide rides 70 percent as bicarbonate, 23 percent on hemoglobin and 7 percent dissolved.

Hemostasis seals a leak in three overlapping steps: vascular spasm, then the platelet plug, then coagulation. The plug grows by positive feedback, as active platelets release ADP and thromboxane A₂ to call in more. Aspirin blocks thromboxane, which weakens that step. Coagulation runs a cascade of clotting factors; the intrinsic and extrinsic paths join a common path, and the end is thrombin turning fibrinogen into fibrin threads. It needs calcium and vitamin K. Later plasmin breaks the clot up.

Blood type comes from antigens on your red cells, and the rule that drives everything is this: your plasma holds antibodies against any antigen you lack. A has A and anti-B. B has B and anti-A. AB has both and no ABO antibodies, so it is the universal recipient. O has neither and both antibodies, so it is the universal donor of red cells. A mismatch causes agglutination and then hemolysis. On top of ABO is the Rh system, where only the D antigen is routinely tested. An Rh-negative person makes anti-D only after meeting Rh-positive blood, which is why a second Rh-positive pregnancy risks hemolytic disease of the newborn, and why Rh immune globulin is given.

The heart sits in the mediastinum, wrapped in the pericardium, whose fluid lets it beat without rubbing. It is two pumps bolted together. The right heart takes blood low in oxygen from the body and sends it to the lungs. The left heart takes fresh blood from the lungs and sends it to the whole body. The septum keeps them apart. Each side runs atrium, ventricle, artery. The wall is endocardium, myocardium, epicardium, and the myocardium is thickest in the left ventricle, which must make about five times the pressure of the right. The coronary arteries feed the muscle, and a blockage is a myocardial infarction.

The path of one drop is worth chanting: venae cavae, right atrium, tricuspid, right ventricle, pulmonary valve, lungs, pulmonary veins, left atrium, mitral, left ventricle, aortic valve, aorta. The pulmonary and systemic circuits run in series, so both ventricles must move the same amount over time. The artery and vein rule is about direction, not oxygen, and the pulmonary vessels prove it.

Four one-way valves keep blood moving forward. The two atrioventricular valves are the tricuspid on the right and the mitral on the left, tied down by the chordae tendineae and papillary muscles. The two semilunar valves, pulmonary and aortic, have three cups each and need no strings. A stenotic valve will not open; a regurgitant one will not close. Both make a murmur.

The heart is autorhythmic. The sinoatrial node fires 60 to 100 times a minute and sets the pace. The spark runs SA node, AV node, AV bundle, bundle branches, Purkinje fibers. The AV node pauses about a tenth of a second so the atria can finish filling the ventricles, and it is the backup pacemaker at 40 to 60. The ventricles squeeze from the apex up.

One beat alternates systole and diastole, taking about 0.8 seconds at 75 beats a minute, mostly diastole. The phases run atrial systole, isovolumetric contraction, ventricular ejection, isovolumetric relaxation, ventricular filling. S1 is the AV valves closing and S2 the semilunar valves closing. Stroke volume is EDV minus ESV, and cardiac output is heart rate times stroke volume, about 5 L a minute at rest.

The ECG records the electrical events, not the beat. The P wave is atrial depolarization, the QRS complex is ventricular depolarization, and the T wave is ventricular repolarization. Atrial repolarization hides inside the QRS. The PR interval holds the AV pause, so a long one is a heart block.

Every vessel has three tunics around a lumen. The intima is lined by endothelium, smooth and non-stick, and it signals. The media is smooth muscle and does vasoconstriction and vasodilation. The externa is collagen and anchors. Arteries carry blood away under high pressure with thick stretchy walls. Veins carry it back with thin walls and one-way valves, and they hold about two-thirds of your blood as the reservoir. Capillaries are one endothelial cell thick, and they are the only place where things are swapped.

Blood pressure is written systolic over diastolic, typically 120/80 mm Hg. Pulse pressure is the difference, and mean arterial pressure is the diastolic plus a third of the pulse pressure. Blood flows down a pressure gradient, and flow equals pressure difference divided by resistance. Resistance goes as 1 over the radius to the fourth, so halving the radius raises resistance 16 times. That makes the muscular arterioles the main resistance vessels.

Capillary exchange is a tug-of-war. Hydrostatic pressure, about 35 mm Hg at the arteriolar end, pushes fluid out. Colloid osmotic pressure from albumin, about 25 mm Hg, pulls it in. So filtration wins at the start. By the venule end hydrostatic pressure has dropped to about 17, so reabsorption wins. About 85 percent returns to the blood and the lymphatics carry the other 15 percent back. An imbalance gives edema, from high hydrostatic pressure, low albumin, or blocked lymph drainage.

A portal system passes two capillary beds in a row. The hepatic portal system sends nutrient-rich blood from the gut through the liver first. Anastomoses, like the circle of Willis, give backup routes. Venous return must equal cardiac output over time, and with almost no pressure left it relies on the skeletal muscle pump, the respiratory pump, one-way valves and venoconstriction. When they fail you get fainting, varicose veins and deep vein thrombosis.

The lymphatic system has three jobs. Fluid balance returns about 3 liters a day of leaked fluid, which becomes lymph once inside a lymphatic vessel. Fat absorption happens through lacteals in the small intestine, carrying milky chyle. Immune defense houses the lymphocytes and filters lymph through checkpoints. Lymph flows one way with no pump: capillaries, vessels, nodes, trunks, then the small right lymphatic duct or the large thoracic duct, into the subclavian veins. Primary lymphoid organs are the red bone marrow and thymus, where lymphocytes mature. Secondary organs are the lymph nodes, spleen, tonsils and MALT, where they fight.

Immunity comes in two styles arranged as three lines of defense. Innate immunity is fast, general and has no memory. Adaptive immunity is slow at first, exact, and it remembers. The first line is barriers: skin, mucous membranes, the acid mantle, lysozyme, stomach acid and normal flora. The second line is inside and still general: phagocytes, natural killer cells, inflammation, fever, interferons and complement. The third line is adaptive: T cells, B cells, antibodies and memory cells. Only the third line has memory.

Inflammation shows four cardinal signs: rubor, calor, tumor, dolor. Histamine from mast cells causes vasodilation, giving redness and heat, and makes capillaries leakier, giving swelling, and swelling pressure plus the chemicals give pain. Phagocytes arrive by chemotaxis and squeeze out by diapedesis, neutrophils first and macrophages next. Body-wide, pyrogens reset the hypothalamus and cause fever, and the marrow raises white cells, which is leukocytosis.

T cells run cell-mediated immunity and mature in the thymus. They are blind to free antigen and only act when antigen is presented on an MHC molecule. MHC I is on every cell with a nucleus and shows what is inside. MHC II is on antigen-presenting cells. Helper T cells, CD4, read MHC II and release cytokines that switch on the rest. Cytotoxic T cells, CD8, read MHC I and kill with perforin and granzymes.

B cells run humoral immunity and mature in bone marrow. On meeting antigen they divide into plasma cells, each making thousands of antibodies a second, and memory B cells. An antibody is Y-shaped with a variable region that binds one antigen. Antibodies tag and disable four ways: neutralize, agglutinate, activate complement, opsonize. The first meeting gives a slow primary response led by IgM. A later meeting gives a fast, strong secondary response led by IgG, which is the whole idea behind vaccination.

Acquired immunity sorts on two questions. Who made the antibodies? Yours is active, slow but lasting with memory. Someone else's is passive, instant but short with no memory. How did the exposure happen? Through life is natural; through medicine is artificial. Two questions, four boxes.

Worth memorizing

How to reason through the question types

The traps people fall into

Theme 7 · Chapters 22 to 26Exchange and balance

What to know

The airway splits into two zones. The conducting zone is the plumbing: nose, pharynx, larynx, trachea, bronchi and bronchioles. It carries, warms, moistens and filters air but never trades gases. The respiratory zone is respiratory bronchioles, alveolar ducts and alveoli, where the trade happens. The air path is nose, pharynx, larynx, trachea, bronchi, bronchioles, alveoli. The epiglottis guards the larynx when you swallow, and C-shaped cartilage rings hold the trachea open. The mucociliary escalator sweeps trapped dirt up and out.

There are about 300 million alveoli, giving about 70 square meters of surface. Gases cross the respiratory membrane, about 0.5 micrometers thick and made of just three layers: the alveolar wall of type I cells, the fused basement membranes, and the capillary wall. Type II cells make surfactant, which lowers surface tension and keeps the sacs from collapsing. Thickening the membrane, as fluid does in pulmonary edema or scar does in fibrosis, makes oxygen travel farther and leaves a person short of breath.

You do not suck air in. Boyle's law says pressure falls as volume rises, so you enlarge the chest and air follows. Inspiration is active: the diaphragm flattens and the external intercostals lift the ribs, which lowers intrapulmonary pressure below the outside air. Quiet expiration is passive: the muscles relax and the stretched lungs recoil. The intrapleural pressure stays negative, which is what holds the lungs to the chest wall.

In a gas mix each gas adds its own partial pressure, and each moves on its own from high to low. Alveolar air is about 104 mmHg oxygen and 40 mmHg carbon dioxide. Blood arriving from the body is about 40 and 45. So in external respiration oxygen moves in and carbon dioxide moves out. In the tissues the numbers flip, and internal respiration runs the arrows backward. Oxygen rides mostly on hemoglobin, and the S-shaped dissociation curve shifts so a warm, acidic, carbon-dioxide-rich tissue gets more oxygen. The pH and carbon dioxide part of that shift is the Bohr effect. Carbon dioxide travels mostly as bicarbonate, made inside the red cell by carbonic anhydrase, which is what ties breathing to blood pH.

Spirometry splits breathing into four volumes: tidal about 500 mL, inspiratory reserve about 3000, expiratory reserve about 1100, and residual about 1200, which never leaves. A capacity adds volumes. Vital capacity is tidal plus both reserves, about 4600 mL. Total lung capacity adds the residual, about 5800 mL. About 150 mL of each breath stays in the conducting airways as anatomical dead space. The FEV₁/FVC ratio splits the two disease families: a low ratio means obstructive, and small volumes with a normal ratio mean restrictive.

The digestive system has two groups of organs. The alimentary canal is the tube food passes through: mouth, pharynx, esophagus, stomach, small intestine, large intestine, anus, about nine meters long. The accessory organs are helpers food never passes through: teeth, tongue, salivary glands, liver, gallbladder, pancreas. Six processes cover everything: ingestion, propulsion, mechanical digestion, chemical digestion, absorption, defecation, with secretion running through all of them.

The wall has four layers from the lumen out: mucosa, submucosa, muscularis externa, serosa or adventitia. Two muscle sheets make two motions. Peristalsis is a traveling wave that pushes food forward, squeezing behind and relaxing ahead. Segmentation squeezes in place to mix chyme and press it against the absorbing wall. Thick rings of muscle form sphincters. And hold the big idea: the lumen is really outside the body, so food only truly enters you once it crosses the wall.

The stomach has four regions: cardia, fundus, body, pylorus. Rugae let it stretch, and a third oblique muscle layer lets it churn food into chyme. Its gland cells each make one thing. Surface mucous cells make the thick bicarbonate-rich protective mucus. Parietal cells make hydrochloric acid and intrinsic factor. Chief cells make pepsinogen. G cells make gastrin. Acid drives pH down to about 1.5 to 2, which turns pepsinogen into pepsin. The mucosal barrier keeps the stomach from digesting itself three ways: bicarbonate mucus, tight junctions, and surface cells replaced every few days.

The small intestine is duodenum, jejunum, ileum, and it is built for surface. Three amplifiers stack: circular folds, then villi, then microvilli, which is the brush border. Together they give about 200 square meters, more than 500 times a plain tube. Inside one villus are capillaries, which carry sugars and amino acids to the liver, and one central lacteal, which takes in fat. Intestinal crypts make the replacement cells.

The helpers pour in from the side. Salivary glands wet food and start starch with salivary amylase. The liver makes bile, whose bile salts emulsify fat, breaking blobs into droplets. The gallbladder stores and concentrates bile and releases it when cholecystokinin signals. The pancreas makes the most complete juice, with amylase, lipase, trypsin, chymotrypsin and nucleases, plus plenty of bicarbonate to cancel stomach acid.

Chemical digestion is hydrolysis. Carbohydrates become single sugars, finished by brush-border maltase, sucrase and lactase. Proteins become amino acids, finished by brush-border peptidases. Nucleic acids become bases, pentose sugars and phosphate ions. Fat is the special case: bile salts emulsify, lipase cuts, micelles ferry the pieces in, and the cell rebuilds them into chylomicrons, which are too big for a capillary and so go into the lacteal. That is why fat travels by lymph first.

Metabolism is every reaction in the body. Anabolism builds by dehydration synthesis and is endergonic. Catabolism breaks down by hydrolysis and is exergonic. ATP is the shared currency, and energy coupling links what pays out to what costs. Electrons ride on NAD⁺ and FAD, becoming NADH and FADH₂.

Cellular respiration runs four stages in two places. Glycolysis in the cytoplasm needs no oxygen and nets 2 ATP plus 2 NADH, splitting glucose into two pyruvate. Pyruvate oxidation in the matrix cuts off a carbon as carbon dioxide and makes acetyl CoA. The citric acid cycle in the matrix frees the rest as carbon dioxide, makes 2 ATP, and loads many carriers. Oxidative phosphorylation on the inner membrane makes about 26 to 28 ATP, for about 30 to 32 in all. Oxygen is the final electron acceptor and forms water. Without it the chain backs up and the cell falls back on fermentation, which keeps glycolysis running by making lactic acid and yields only 2 ATP.

Fuel arrives in bursts, so the body runs two metabolic states. The absorptive state stores, led by insulin, using glycogenesis and lipogenesis. The postabsorptive state releases, led by glucagon, using glycogenolysis, lipolysis and gluconeogenesis. The liver is the hub. The point is the brain, which runs almost only on glucose and cannot store fuel, so glucose sparing sends most tissues to fatty acids, and in long starvation the liver makes ketone bodies.

Food gives six nutrient classes. The three macronutrients give energy: carbohydrates and proteins at 4 kcal per gram, lipids at 9. Vitamins, minerals and water give none and are still essential. Vitamins split by how they dissolve. Fat-soluble A, D, E and K are stored and can reach toxic levels. Water-soluble B-complex and C are not stored and need a steady daily supply. Energy balance compares calories in with calories out. Out has three parts, largest first: basal metabolic rate at 60 to 75 percent, the thermic effect of food at about 10 percent, and physical activity. A pound of fat stores about 3,500 kcal.

The urinary system has four organs: two kidneys, two ureters, one bladder, one urethra. The kidneys get 20 to 25 percent of cardiac output and filter about 180 liters a day, taking back over 99 percent so only 1 to 2 liters leave. They also help set blood pressure, drive red cell making and turn on vitamin D. Inside, the layers go capsule, cortex, medulla with its pyramids. Urine drains papilla, minor calyx, major calyx, renal pelvis, ureter, and is not changed after the papilla. The kidney has two capillary beds in series: the high-pressure glomerulus and the low-pressure peritubular capillaries.

Each kidney holds about one million nephrons. The renal corpuscle filters across a three-layer filtration membrane: the fenestrated capillary wall, the negatively charged basement membrane, and podocyte slits. Normal filtrate is plasma with no protein. The tubule runs proximal convoluted tubule, loop of Henle, distal convoluted tubule, collecting duct. Three steps make urine: filtration from blood to tubule at a GFR of about 125 mL a minute, reabsorption from tubule to blood, and secretion from blood to tubule. The proximal tubule takes back about 65 percent of water and sodium and nearly all glucose and amino acids. The loop makes the medulla salty so water can be pulled back later.

Hormones finish the job. ADH puts aquaporins into the collecting duct, so water is saved and urine is concentrated. The renin-angiotensin-aldosterone system raises pressure: low pressure calls out renin, which makes angiotensin I, which ACE in the lungs turns into angiotensin II, which narrows vessels at once and calls for aldosterone to keep sodium and water. Atrial natriuretic peptide does the reverse when the atria are stretched. Downstream, the micturition reflex fires at about 200 to 400 mL: stretch receptors signal the sacral cord, which contracts the detrusor and opens the internal sphincter, while the brain holds or releases the external sphincter.

Water is about 60 percent of body mass, split two-thirds intracellular and one-third extracellular, and the ECF is about three-quarters interstitial and a quarter plasma. The ECF is rich in sodium and chloride; the ICF is rich in potassium. The sodium-potassium pump keeps that apart, and osmolarity decides where water goes. In and out each run about 2.5 liters a day. Intake is drink, water in food and metabolic water. Output is urine, the only closely controlled route, plus insensible loss from skin and lungs, feces and sweat. Osmoreceptors in the hypothalamus set off thirst and ADH.

Electrolytes are measured in mEq/L. Sodium at 135 to 145 rules ECF volume and is guarded by aldosterone. Potassium at 3.5 to 5.0 sets the resting membrane potential and matters most to the heart. Calcium runs contraction, clotting and nerves, tuned by PTH and vitamin D. Small drifts cause big trouble: low sodium swells brain cells, potassium problems upset heart rhythm, and low calcium gives tetany.

Arterial pH is held at 7.35 to 7.45, because pH bends the shape of proteins and enzymes are proteins. The main buffer is the bicarbonate system, and the reaction is worth knowing by heart. It is strong because it is open at both ends: the lungs control the carbon dioxide and the kidneys control the bicarbonate. Three lines guard pH on three clocks: buffers in seconds, which only hide the acid; the lungs in minutes, which cannot fix a lung-caused problem; and the kidneys in hours to days, the only complete fix. When control fails you get one of four disorders, named by two questions: which way the pH went, and whether the cause changed carbon dioxide or bicarbonate. The memory word is ROME: respiratory means pH and carbon dioxide move opposite, metabolic means pH and bicarbonate move the same way.

Worth memorizing

How to reason through the question types

The traps people fall into

Theme 8 · Chapters 27 and 28Continuity

What to know

Every other system keeps you alive. This one looks past you. Its job is to make a new person, and that takes a gamete carrying exactly half your genetic instructions, so sperm and egg together restore the full set.

The male system makes sperm in the seminiferous tubules of the testes, which hang in the scrotum because sperm making needs a temperature a few degrees cooler than the body core. New sperm cannot swim, so they spend about two weeks maturing and being stored in the epididymis. The road out is epididymis, ductus deferens, ejaculatory duct, urethra, and in males the urethra is shared plumbing. Three glands make most of semen. The seminal vesicles add thick fluid full of fructose to fuel the tails. The prostate adds a milky alkaline fluid so sperm survive acid. The bulbourethral glands add a clear slippery fluid first.

Spermatogenesis never stops after puberty. A spermatogonium is a diploid stem cell, and when it divides one daughter stays a stem cell, so the supply never runs out. The other becomes a primary spermatocyte and enters meiosis. Meiosis I gives two haploid secondary spermatocytes, and meiosis II gives four spermatids. The divisions are equal, so all four are useful. Then spermiogenesis reshapes each one, adding the enzyme-filled acrosome, a mitochondria-packed midpiece and a whip-like flagellum. The whole process takes about 64 to 74 days. Sertoli cells nurse the sperm and form the blood-testis barrier. Leydig cells make testosterone.

The female system makes the egg and also houses a pregnancy. The two ovaries hold the lifetime supply of eggs and release one at ovulation. A uterine tube catches it with finger-like fimbriae, and fertilization usually happens in the outer third of that tube. The uterus has three wall layers: the endometrium that thickens and is shed, the myometrium that squeezes in labor, and the thin outer perimetrium. The cervix opens into the vagina. The ovary is also a gland: the follicle around a ripening egg makes estrogen, and the leftover corpus luteum makes progesterone.

Oogenesis uses the same meiosis on a very different schedule. When a primary oocyte finishes meiosis I it divides unequally: one secondary oocyte keeps nearly all the cytoplasm and one tiny polar body gets almost nothing. The same happens in meiosis II, and in humans that second division only finishes if a sperm fertilizes the egg. So one cell in gives one useful egg plus polar bodies. The reason is supplies: an egg must carry enough cytoplasm, food and cell parts to start a new life. The timeline is the strangest in the body. All eggs start meiosis I before birth and then pause, so an egg released at forty has been frozen for four decades, which helps explain why chromosome errors rise with the mother's age. The supply falls from 1 to 2 million at birth to about a thousand follicles at menopause.

The menstrual cycle lasts about 28 days and is two cycles in step, one in the ovary and one in the uterus. Four hormones run it: FSH and LH from the pituitary, estrogen and progesterone from the ovary. Day 1 starts menstruation. In the follicular phase, FSH grows follicles, one takes the lead, and its estrogen rebuilds the lining. Rising estrogen then sets off the LH surge around day 14, which causes ovulation. In the luteal phase, the corpus luteum's progesterone keeps the lining rich. With no pregnancy it shrinks, both hormones drop, and the lining is shed. One detail is worth holding: estrogen gives negative feedback most of the cycle, but when it climbs high and stays high it flips to positive feedback and fires the surge.

Meiosis exists to halve the chromosome number. Body cells are diploid with 46 chromosomes in 23 pairs. If two 46-chromosome cells joined, the count would double each generation. So meiosis makes haploid gametes with 23, and fertilization restores 46. It takes two divisions with the DNA copied only once. Meiosis I pulls homologous pairs apart, and that is the halving step. Meiosis II splits the sister copies. Compare mitosis: one division, two identical diploid cells. Meiosis also reshuffles genes two ways. Crossing over swaps matching pieces in meiosis I. Independent assortment lines up and splits each of the 23 pairs at random. Nondisjunction, when a pair fails to split, gives a gamete the wrong number.

Fertilization happens in the ampulla of the uterine tube, within about a day of ovulation, and the egg is fertilizable for only about 12 to 24 hours. Of hundreds of millions of sperm only a few hundred arrive, after capacitation readies their outer covers. The egg is wrapped in the corona radiata and, under it, the zona pellucida. The acrosome reaction spills digesting enzymes to tunnel through the zona, and it takes many sperm to open a path even though only one gets in. Two locks then stop polyspermy. The fast block changes the charge across the egg surface. The slow block, or cortical reaction, hardens the zona. Only now does the egg finish meiosis II, the two sets of 23 join to make 46, and the zygote exists. The sperm's X or Y set the sex at that moment.

Cleavage divides the zygote again and again without the ball getting bigger, because the same cytoplasm is split into smaller cells. By about day 4 it is a solid morula of about 16 cells. By about day 5 fluid hollows it into a blastocyst, whose outer trophoblast becomes the placenta and membranes while the inner cell mass becomes the embryo. Implantation runs about days 6 to 10, after the blastocyst hatches from the zona so its trophoblast can stick to the endometrium. The trophoblast at once makes human chorionic gonadotropin, which keeps the corpus luteum making progesterone so the lining is not shed, and which is what a pregnancy test looks for.

In the third week, gastrulation at the primitive streak forms three primary germ layers, and all 200-plus cell types come from them. Ectoderm is the outside and the wiring: epidermis and the whole nervous system. Mesoderm is everything in the middle: muscle, bone, blood, heart, vessels, kidneys and dermis. Endoderm is the innermost linings and the glands budding off them: gut and airway lining, liver and pancreas. Then organogenesis builds organs through week 8. One early step is ectoderm folding into the neural tube, which closes so early that folic acid must already be there.

Growth splits at the end of week 8. The embryonic period, weeks 1 to 8, lays down every major organ, and a teratogen does its worst harm to body shape in weeks 3 to 8. The fetal period, week 9 on, mostly grows and finishes. A full term is about 38 weeks from fertilization or 40 from the last menstrual period, in three trimesters.

The placenta is built from the embryo's trophoblast tissue plus the mother's endometrium. Finger-like chorionic villi reach into pools of her blood, and across that thin barrier gases, food and wastes cross while the two bloodstreams never mix. It also takes over hormone making from the corpus luteum. Her blood volume rises 30 to 50 percent. Labor is driven by oxytocin positive feedback and runs dilation, expulsion, placental.

You carry two alleles of most genes. Two matching alleles is homozygous; two different is heterozygous. The pair is the genotype and the visible trait is the phenotype. A dominant allele shows with one copy and hides a recessive one, which shows only when both copies are recessive. A Punnett square gives the odds. Two carriers, Bb times Bb, give 1 BB : 2 Bb : 1 bb, which is 3 brown to 1 blue. Read it as a chance, not a promise: each pregnancy starts fresh, like a coin flip. Some alleles are codominant, as in type AB blood, and genes on the X chromosome make sex-linked patterns.

Worth memorizing

How to reason through the question types

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