Human Physiology and Anatomy

Endocrine hormones

Endocrine hormones are chemical messengers that ductless glands secrete into the blood, so they can act on target cells far from their site of release. Their chemical class determines how they are made, carried and received. Peptide hormones are chains of amino acids that are synthesised as precursors, stored in secretory granules and bind to receptors on the cell surface, as insulin and oxytocin do. Steroid hormones such as cortisol, aldosterone and testosterone are derived from cholesterol, are lipophilic, and act through intracellular receptors. Many hormones are controlled along a hypothalamic-pituitary axis. The hypothalamus releases a releasing hormone, the anterior pituitary releases a tropic hormone, and the target gland releases its end hormone, which feeds back to suppress the upstream steps. Thyroid stimulating hormone is made by the thyrotroph cells of the anterior pituitary, not by the thyroid itself, and it stimulates the thyroid to release T4 and T3. In the islets of Langerhans, beta cells secrete insulin to lower blood glucose, alpha cells secrete glucagon to raise it, and delta cells secrete somatostatin. The adrenal gland has two parts with different secretions. The medulla releases epinephrine, and the cortex releases glucocorticoids such as cortisol and mineralocorticoids such as aldosterone. Oxytocin is not an adrenal hormone; it is released from the posterior pituitary.

• tropic hormone: a hormone whose target is another endocrine gland, such as TSH acting on the thyroid.
• peptide hormone: a hormone built from amino acids, such as insulin, which is a 51-residue two-chain peptide.
• steroid hormone: a hormone derived from cholesterol, such as testosterone.

Skeletal system anatomy

The adult skull has eight cranial bones that enclose the brain: the frontal, two parietals, two temporals, occipital, sphenoid and ethmoid. The occipital bone forms the posterior and inferior part of the cranium and contains the foramen magnum. The mandible is a facial bone, and the coccyx and sternum belong to the vertebral column and the thoracic skeleton, so none of them is a cranial bone. Bone is continuously remodelled by three main cell types. Osteoblasts form new bone matrix, osteocytes are mature cells embedded in the mineralised matrix that sense load and maintain it, and osteoclasts are large multinucleated cells that resorb bone. Osteoclasts arise from the monocyte-macrophage lineage and dissolve mineral and matrix with acid and proteolytic enzymes such as cathepsin K. Osteocalcin is a protein secreted by osteoblasts, so it is a molecule, not a bone-resorbing cell.

• resorption: the removal of bone tissue by osteoclasts.
• foramen magnum: the opening at the base of the skull through which the spinal cord passes.

Digestive organ functions

Each digestive organ has a specific secretory or storage role, and exam questions often pair an organ with its product. The stomach secretes gastrin from its G cells, the liver synthesises bile, the gallbladder stores and concentrates bile, and the pancreatic islets secrete insulin and glucagon. The stomach is not the source of insulin, glucagon or bile, so each organ must be matched to its own product. The pyloric sphincter is a ring of smooth muscle at the distal end of the stomach. It regulates the passage of chyme into the duodenum, so it lies between the stomach and the duodenum. The cardiac sphincter guards the junction between the oesophagus and the stomach, and the ileocaecal valve separates the ileum from the large intestine.

• chyme: the semifluid mixture of gastric contents that passes from the stomach into the duodenum.
• gallbladder: a storage organ for bile; it does not synthesise bile.

Systemic circulation pathway

Blood circulates in two linked circuits. In the systemic circuit, oxygenated blood leaves the left ventricle through the aorta, flows through the systemic arteries and capillaries, returns through the systemic veins to the vena cavae, and enters the right atrium and then the right ventricle. In the pulmonary circuit, blood leaves the right ventricle through the pulmonary artery, passes through the lungs, returns through the pulmonary veins to the left atrium, and enters the left ventricle. Arteries carry blood away from the heart and veins carry it toward the heart, so the order of vessels and chambers must follow this loop exactly. The pulmonary artery is an exception to the usual rule that arteries carry oxygenated blood, because it carries deoxygenated blood to the lungs. The pulmonary vein is the exception to the rule that veins carry deoxygenated blood, because it returns oxygenated blood to the left atrium.

Skeletal muscle contraction types

Muscle contractions are classified by whether the length of the muscle changes. In an isometric contraction the muscle develops tension without shortening. This occurs when the force generated is not enough to lift the load, so the load does not move. An isotonic contraction involves a change in length against a constant load. An isokinetic contraction keeps the velocity of movement constant, and an isoinertial contraction works against a constant inertial load. In laboratory tests the two basic types are set up in opposite ways. In an isotonic test the tension is held constant while length change is recorded, whereas in an isometric test the length is held fixed while the force generated is recorded.

• isometric: constant length, varying tension.
• isotonic: constant load, varying length.

Blood plasma and serum composition

Plasma is the liquid part of blood that contains the clotting proteins, while serum is the fluid that remains after clotting has taken place. During clot formation fibrinogen is converted to fibrin and is consumed, and platelets are removed together with the clot. Serum therefore lacks fibrinogen and platelets. Albumin, which is the most abundant plasma protein at roughly 35 to 50 g/L, and glucose, which is a small dissolved molecule, remain in serum at normal concentrations. Because fibrinogen and the other clotting factors have been removed, serum does not coagulate on a glass slide. Fresh arterial blood and fresh venous blood both contain fibrinogen and platelets and therefore clot. Depletion of neutrophils alone does not stop clotting, since neutrophils are not needed to form the clot.

• serum: plasma from which the clotting factors have been removed by coagulation.
• fibrinogen: the plasma protein converted to fibrin during clotting; it is present in plasma but absent from serum.

Lung volumes and capacities

The lung volumes are the tidal volume (TV), inspiratory reserve volume (IRV), expiratory reserve volume (ERV) and residual volume (RV). The capacities are sums of these volumes. The vital capacity is VC = TV + IRV + ERV, the inspiratory capacity is IC = TV + IRV, the functional residual capacity is FRC = ERV + RV, and the total lung capacity is TLC = VC + RV. From these definitions, VC - ERV = IC and IC + FRC = TLC, while adding ERV to VC has no meaning as a capacity and FRC is a sum, not a difference. When two of the quantities are known, the third can be found by rearrangement. For example, the expiratory reserve volume equals ERV = VC - (TV + IRV).

• functional residual capacity: the volume left in the lungs at the end of a normal expiration.
• residual volume: the air that remains in the lungs after a maximal expiration.

Skin layer anatomy

The skin consists of layers that lie in a fixed sequence from the surface inward. The outermost layer is the stratum corneum, which is dead, keratinised epidermis. Beneath it lies the viable epidermis, then the dermis, and finally the subcutaneous fat, also called the hypodermis. The epidermis is a stratified squamous epithelium. Its main cell type is the keratinocyte, which is present throughout its layers. Melanocytes are dendritic pigment-producing cells located mainly in the stratum basale. Oxyntic cells belong to the gastric glands of the stomach, and goblet cells belong to the intestinal and respiratory mucosa, so neither is found in the skin.

• stratum corneum: the outermost layer of the epidermis, made of flattened keratinised cells.
• melanocyte: a pigment-producing cell that synthesises melanin.

Blood acid-base balance

The pH of arterial blood in a healthy human is tightly maintained between 7.35 and 7.45, which is slightly alkaline. Values below 7.35 indicate acidaemia or acidosis, and values above 7.45 indicate alkalaemia or alkalosis. The bicarbonate buffer system, together with ventilatory control of carbon dioxide and renal regulation of bicarbonate and hydrogen ions, keeps blood pH within this narrow range.

• acidosis: a pathological state in which blood pH falls below the normal range.
• alkalosis: a pathological state in which blood pH rises above the normal range.

Myocardial infarction

A myocardial infarction is necrosis of heart muscle caused by prolonged ischaemia. It is most often produced by occlusion of a coronary artery, which supplies blood to the heart wall. The occlusion is usually a thrombus that forms over a ruptured atherosclerotic plaque and stops the supply of oxygen and nutrients to the myocardium. Obstruction of arteries that supply the brain causes cerebral ischaemia and stroke, and obstruction of veins that drain the brain causes venous sinus or cerebral venous thrombosis. These conditions are distinct from myocardial infarction, which concerns the coronary arterial supply of the heart.

• ischaemia: reduced blood supply to a tissue, leading to insufficient oxygen delivery.
• coronary artery: an artery that supplies the myocardium.

Skeletal muscle architecture

Skeletal muscles differ in the arrangement of their fibres, which determines their force and shortening properties. In a parallel fibre muscle the fibres are long and run along the length of the muscle. A pinnate muscle has short fibres set obliquely to the tendon. For a given muscle volume, a pinnate muscle contains more fibres and so has a larger physiological cross-sectional area, and its maximum force is proportional to that area. Pinnate muscles therefore produce more force. Long fibres in a parallel muscle allow a greater range and velocity of shortening, so parallel fibre muscles give better shortening. Pinnate muscles give less shortening because their fibres are short.

• physiological cross-sectional area: the sum of the cross-sections of all fibres perpendicular to their long axes.
• pinnate: having fibres arranged obliquely to a central tendon.

Smooth muscle physiology

Smooth muscle is found in the walls of hollow organs, such as the gut, the bladder and blood vessels. Its cells are non-striated, so they lack the sarcomere arrangement that produces striations in skeletal and cardiac muscle. Smooth muscle contraction is involuntary and is controlled by the autonomic nervous system together with local and hormonal signals. Smooth muscle is therefore not made of striated cells, and this is a common trap in questions about muscle types.

• non-striated: lacking the cross-striations seen in skeletal and cardiac muscle.
• involuntary: not under conscious control.

Refractive errors of the eye

In myopia, or short-sightedness, the focal point of the eye falls in front of the retina. This happens when the eye has too much converging power or the eyeball is too long. Myopia is corrected with a concave, or diverging, lens that reduces the converging effect so that the focus falls on the retina. In hypermetropia, or long-sightedness, the focal point falls behind the retina, and a convex (converging) lens is used as the correction. The power of a lens in dioptres is P = 1/f, where f is the focal length in metres, and a concave lens has negative power.

• myopia: short-sightedness, with the image focused in front of the retina.
• concave lens: a diverging lens used to correct myopia.

Brain white and gray matter anatomy

White matter consists mainly of myelinated axons that connect different regions of the nervous system, whereas gray matter consists of neuronal cell bodies, dendrites, synapses and unmyelinated fibres. The cerebral cortex and the basal ganglia are gray matter structures, and the limbic system is a functional grouping of gray matter areas such as the hippocampus and amygdala. The corpus callosum is a broad band of myelinated commissural fibres that links the left and right cerebral hemispheres, so it is the region that is composed primarily of white matter.

• white matter: tracts of myelinated axons, which appear white because of their lipid-rich myelin.
• commissure: a bundle of fibres that connects corresponding areas of the two hemispheres.

Myelinated vs unmyelinated axon conduction

In an unmyelinated axon the action potential changes the membrane potential along the whole length of the membrane, so Na+ enters and K+ leaves across the entire surface. In a myelinated axon, myelin insulates the internodal segments and ionic currents occur only at the nodes of Ranvier, which is the basis of saltatory conduction. For axons of equal diameter and length, the unmyelinated axon has a greater ion flux and therefore a greater ATP requirement, since the Na+/K+ pump must restore the ion gradients over a larger membrane area. Myelination thus increases conduction speed while reducing metabolic cost.

• saltatory conduction: the jumping of the action potential from one node of Ranvier to the next.
• node of Ranvier: a gap in the myelin sheath where the axonal membrane is exposed.

Circulation time and cardiac output

The mean transit time through a compartment equals its blood volume divided by the flow through it, t = V/Q. In steady state, the flow through each of the two circuits equals the cardiac output, so the time taken for blood to pass from the right ventricle to the left ventricle depends on the pulmonary blood volume and the cardiac output. Because the pulmonary circuit carries the entire cardiac output, it is the systemic volume that determines the time for a full circulation through the body, and the pulmonary volume determines the time through the lungs. Units must be consistent, so volumes in litres and flow in litres per minute should be converted to seconds before the result is quoted.

• transit time: the average time a blood element takes to pass through a vascular compartment.
• cardiac output: the volume of blood pumped by one ventricle per minute.

Alveolar ventilation and dead space

Each tidal breath includes anatomical dead space, which is the volume of the conducting airways where no gas exchange occurs. Only the remainder reaches the alveoli. Alveolar ventilation is therefore \dot V_A = (V_T - V_D)\,f, where V_T is the tidal volume, V_D is the dead space volume and f is the breathing rate. Pulmonary perfusion equals the cardiac output, which is the product of heart rate and stroke volume. The ventilation to perfusion ratio is \dot V_A/\dot Q, and in a healthy lung its overall average is close to 0.8.

• anatomical dead space: airway volume that does not take part in gas exchange.
• ventilation to perfusion ratio: the ratio of alveolar ventilation to pulmonary blood flow, which determines gas exchange efficiency.

Blood volume and hematocrit

Hematocrit is the fraction of whole blood volume that is occupied by red blood cells. The plasma fraction is therefore one minus the hematocrit, so the plasma volume equals (1 - \text{Hct}) \times V_{blood}. The total blood volume is usually estimated from body weight, and in adults it is roughly 70 mL per kilogram. Hence, if a blood volume is calculated from a given weight, the red cell volume is the hematocrit multiplied by that blood volume, and the plasma volume is the remainder.

• hematocrit: the volume percentage of red blood cells in whole blood.
• plasma volume: the volume of blood excluding red cells.

Fick principle cardiac output

The Fick principle states that the oxygen consumption of a tissue or of the whole body equals the cardiac output multiplied by the arteriovenous difference in oxygen content, so \dot V_{O_2} = CO \times (C_aO_2 - C_vO_2). Rearranged, cardiac output equals oxygen uptake divided by this difference. The oxygen taken up by the lungs per minute is the minute ventilation multiplied by the difference between inspired and expired oxygen fractions. If all oxygen absorbed in the lungs enters the blood, the change in blood oxygen content over one minute is this uptake divided by the cardiac output. Oxygen content is usually expressed in volume percent, meaning millilitres of oxygen per 100 mL of blood.

• volume percent (vol%): millilitres of gas per 100 mL of blood.
• arteriovenous difference: the difference between arterial and venous oxygen content.