EXAM STRATEGY & IMPORTANT QUESTIONS GUIDE

Organisation of the Nervous System:
The nervous system is organised both anatomically and functionally.
Anatomical division: the CNS consists of the brain and the spinal cord, while the PNS consists of 12 pairs of cranial nerves, 31 pairs of spinal nerves and the autonomic ganglia.
Functional division: the somatic 🔊 nervous system mediates voluntary control of skeletal muscle and sensation from the skin, while the ANS controls smooth muscle, cardiac muscle and glands and is subdivided into the sympathetic, parasympathetic and enteric branches.

Structure of a Neuron:
The neuron is the functional unit of the nervous system and consists of the following parts.
The dendrites 🔊 are short, branched cytoplasmic processes that receive incoming signals.
The cell body (soma or perikaryon 🔊) contains the nucleus and the Nissl bodies, which are aggregates of rough endoplasmic reticulum.
The axon 🔊 is a single long cytoplasmic process that transmits the impulse away from the cell body; it may be myelinated or unmyelinated.
The axon hillock is the trigger zone where the action potential originates.
The myelin sheath 🔊 is a lipid-rich insulating layer formed by Schwann cells in the PNS and by oligodendrocytes in the CNS.
The nodes of Ranvier 🔊 are gaps in the myelin that permit saltatory conduction.
The synaptic terminals at the end of the axon release the neurotransmitter into the synaptic cleft.
By the number of processes, neurons are classified as unipolar, bipolar (as in the retina and olfactory epithelium) and multipolar (most CNS neurons).

Classification of Neuroglia:
The neuroglial cells of the CNS are four in number.
Astrocytes 🔊 maintain the BBB, buffer extracellular K⁺ and provide metabolic support.
Oligodendrocytes 🔊 form the myelin sheath around CNS axons.
Microglia 🔊 are resident immune cells that perform surveillance and phagocytosis.
Ependymal 🔊 cells line the ventricles and, through the choroid plexus, produce cerebrospinal fluid.
In the PNS, Schwann cells form myelin and satellite cells support sensory and autonomic ganglia.

Classification of Nerve Fibres (Erlanger–Gasser):
The following table summarises the classical fibre types.

Type	Diameter (µm)	Myelinated?	Conduction speed (m/s)	Principal function
Aα	12 – 22	Yes	70 – 120	Somatic motor; proprioception
Aβ	5 – 12	Yes	30 – 70	Touch and pressure
Aγ	3 – 6	Yes	15 – 30	Motor to muscle spindle
Aδ	1 – 5	Yes (thin)	12 – 30	Fast (sharp) pain and cold
B	< 3	Yes	3 – 15	Pre-ganglionic autonomic
C	0.4 – 1.2	No	0.5 – 2	Slow (dull) pain; post-ganglionic autonomic

Resting Membrane Potential:
The resting membrane potential of a typical neuron is about −70 mV inside relative to outside. It is maintained by three factors: the Na⁺/K⁺ ATPase 🔊 pump (three Na⁺ out and two K⁺ in per ATP), K⁺ leak channels allowing K⁺ to diffuse out down its gradient, and organic anions that remain trapped inside the cell.

Phases of the Action Potential:
(1) Resting phase: the membrane is at −70 mV and both Na⁺ and K⁺ channels are closed.
(2) Depolarisation 🔊: when a stimulus opens voltage-gated Na⁺ channels, Na⁺ rushes in; once the membrane reaches threshold (−55 mV), the rapid Na⁺ influx reverses the membrane potential to about +35 mV.
(3) Repolarisation: the Na⁺ channels inactivate, and voltage-gated K⁺ channels open; K⁺ efflux returns the membrane toward −70 mV.
(4) Hyperpolarisation: the K⁺ channels close slowly, producing a brief overshoot below −70 mV.
(5) Return to resting: the Na⁺/K⁺ pump restores the original ionic gradients.
Two refractory periods follow — the absolute refractory period, when no second action potential can be generated, and the relative refractory period, when a stronger than usual stimulus is required.

Conduction of the Nerve Impulse:
In unmyelinated fibres, continuous conduction occurs, in which each adjacent membrane segment depolarises sequentially; this is slow. In myelinated fibres, saltatory conduction 🔊 occurs, in which the action potential jumps between successive NoR, making conduction much faster and energy-efficient.
According to the all-or-none law, the action potential either occurs fully or not at all; a stronger stimulus produces a higher frequency of impulses rather than a larger amplitude.

The Synapse:
There are two types of synapse.
A chemical synapse uses transmitters released from pre-synaptic vesicles, and is unidirectional with a synaptic delay of about 0.5 ms.
An electrical synapse uses gap junctions, is bidirectional and almost instantaneous.
The sequence of events at a chemical synapse is as follows. (1) The action potential reaches the pre-synaptic terminal. (2) Voltage-gated Ca²⁺ channels open and Ca²⁺ flows in. (3) Synaptic vesicles fuse with the pre-synaptic membrane and release the neurotransmitter into the cleft. (4) The transmitter binds its post-synaptic receptor. (5) Ion channels open, producing either an EPSP or an IPSP. (6) The transmitter is inactivated by an enzyme such as AChE, by re-uptake into the pre-synaptic terminal, or by diffusion away from the cleft.

Major Neurotransmitters:

Transmitter	Class	Principal action
Acetylcholine	Amine / ester	Neuromuscular junction, parasympathetic, memory in CNS
Noradrenaline and adrenaline	Catecholamine	Sympathetic action and arousal
Dopamine	Catecholamine	Reward; motor control (decreased in Parkinson's disease)
Serotonin (5-HT)	Indoleamine	Mood, sleep, appetite
GABA	Amino acid	Principal inhibitory transmitter of the CNS
Glutamate	Amino acid	Principal excitatory transmitter of the CNS
Glycine	Amino acid	Inhibitory transmitter of the spinal cord
Endorphins and substance P	Neuropeptides	Pain modulation

1. Cerebrum:
The cerebrum is the largest part of the brain and consists of two hemispheres connected by the corpus callosum 🔊. Each hemisphere has an outer grey matter (the cortex), inner white matter, and deep masses of grey matter known as the basal ganglia.
Lobes and their functions:
The frontal lobe contains the motor cortex (precentral gyrus), is responsible for planning and judgement, and includes Broca's area for motor speech.
The parietal lobe contains the somatosensory cortex (postcentral gyrus) and mediates spatial awareness.
The temporal lobe contains the auditory cortex, the hippocampus 🔊 (memory) and Wernicke's area.
The occipital lobe is responsible for vision.
The insula mediates taste and visceral sensation.
The basal ganglia include the caudate, putamen, globus pallidus, substantia nigra and subthalamic nucleus, and they control voluntary movement; degeneration of the substantia nigra produces Parkinson's disease.

Diencephalon (between the cerebrum and the brainstem):
The thalamus 🔊 is the main sensory relay to the cerebral cortex, while the hypothalamus 🔊 controls temperature, hunger, thirst, emotions, the autonomic nervous system and, through its releasing hormones, the pituitary gland.

2. Brainstem:
The brainstem has three parts.
The midbrain contains the cerebral peduncles, the superior colliculi (vision), the inferior colliculi (hearing) and the substantia nigra.
The pons 🔊 is the bridge between the medulla and the midbrain; it contains the apneustic and pneumotaxic respiratory centres and gives origin to cranial nerves V – VIII.
The medulla oblongata 🔊 contains the vital cardiac, vasomotor, respiratory (dorsal and ventral), vomiting and deglutition centres; it is also the site of pyramidal decussation and gives origin to cranial nerves IX – XII.
The reticular formation regulates the sleep–wake cycle, arousal and consciousness.

3. Cerebellum ("Little Brain"):
The cerebellum 🔊 lies in the posterior cranial fossa and consists of two hemispheres connected by the vermis. Its divisions are the flocculonodular lobe (balance) and the anterior and posterior lobes (coordination).
Its principal functions are coordination of voluntary movement, maintenance of balance and posture (vestibulocerebellum), regulation of muscle tone and motor learning.
Lesions of the cerebellum produce ataxia 🔊, dysmetria, intention tremor and nystagmus.

Meninges (from outside inwards):
The dura mater 🔊 is the tough outer fibrous layer; it is double-layered and houses the dural venous sinuses.
The arachnoid mater 🔊 is the middle layer and resembles a spider web; beneath it lies the subarachnoid space containing CSF.
The pia mater 🔊 is the delicate inner layer that is closely adherent to the surface of the brain and spinal cord.
The meningeal spaces are the epidural (between skull and dura, the site of extradural haemorrhage), the subdural (between dura and arachnoid, the site of subdural haemorrhage), and the subarachnoid space (between arachnoid and pia) which contains the CSF and cerebral vessels and is the site of lumbar puncture at L3 – L4.

Ventricles of the Brain:
There are four CSF-filled cavities lined by ependymal cells: the two lateral ventricles (one in each cerebral hemisphere), the third ventricle (between the two thalami), and the fourth ventricle (between the brainstem and the cerebellum).
They communicate with each other as follows: the lateral ventricles drain into the third ventricle through the foramen of Monro; the third ventricle drains into the fourth through the cerebral aqueduct of Sylvius 🔊; and the fourth ventricle opens into the subarachnoid space through the paired foramina of Luschka 🔊 and the single foramen of Magendie 🔊.

Cerebrospinal Fluid (CSF):
Production: about 500 mL per day by the choroid plexus of the lateral, third and fourth ventricles.
Volume: the total volume is 100 – 150 mL and it is recycled three to four times a day.
Composition: CSF is clear and colourless, with a low protein content (15 – 45 mg/dL), glucose of 50 – 80 mg/dL (about two-thirds of plasma), a sodium concentration similar to plasma and lower potassium and calcium.
Circulation path: choroid plexus → lateral ventricles → foramen of Monro → third ventricle → aqueduct of Sylvius → fourth ventricle → foramina of Luschka and Magendie → subarachnoid space → arachnoid villi → superior sagittal sinus → venous blood.
Functions: CSF acts as a mechanical cushion that protects the brain from shock (by Archimedean buoyancy), supplies oxygen and nutrients while removing metabolic wastes, helps maintain a constant ionic environment (as part of the BBB), regulates ICP, and provides a diagnostic window (lumbar puncture for meningitis, subarachnoid haemorrhage or multiple sclerosis).
Hydrocephalus 🔊 is accumulation of CSF, leading to raised ICP.

Gross Structure:
The spinal cord is approximately 45 cm long in men and 42 cm in women. It extends from the medulla oblongata above to the lower border of L1 – L2 vertebra in the adult. It ends as the conus medullaris 🔊 and is continued below as the filum terminale, while the lumbar and sacral nerve roots form the cauda equina 🔊 below L2. It has two enlargements — the cervical enlargement (C3 – T2) for the upper limb, and the lumbar enlargement (L1 – S2) for the lower limb — and gives off 31 pairs of spinal nerves.
Internally, a central canal containing CSF is surrounded by an H-shaped area of grey matter (cell bodies) which is in turn surrounded by the peripheral white matter carrying the ascending and descending tracts. The horns of grey matter are the posterior (sensory), the anterior (motor) and the lateral (autonomic, only between T1 and L2).

Ascending (Afferent / Sensory) Tracts:
The spinothalamic tract carries pain, temperature and crude touch. The dorsal column (the fasciculus gracilis and fasciculus cuneatus) carries fine touch, conscious proprioception and vibration. The spinocerebellar tract carries unconscious proprioception to the cerebellum.

Descending (Efferent / Motor) Tracts:
The pyramidal (corticospinal) tract carries voluntary motor commands; about 80 % of its fibres cross over in the medulla at the pyramidal decussation.
The extrapyramidal tracts (rubrospinal, reticulospinal, vestibulospinal and tectospinal) regulate posture, muscle tone and equilibrium.

The Reflex Arc:
A reflex arc is the simplest functional unit of the nervous system and produces an involuntary, rapid response.
The five components are as follows.
(1) The receptor detects the stimulus.
(2) The afferent (sensory) neuron carries the impulse to the spinal cord.
(3) The integrating centre is in the spinal cord (or the brainstem for cranial reflexes).
(4) The efferent (motor) neuron carries the response back.
(5) The effector is the muscle or gland that produces the response.

Reflexes are of two types. A monosynaptic reflex has a single synapse between the afferent and efferent neurons, as in the knee-jerk (patellar) stretch reflex. A polysynaptic reflex involves one or more interneurons, as in the flexor withdrawal reflex to a painful or hot stimulus.
Clinically useful reflexes include the corneal blink, pupillary light, gag, cough, sneeze, knee-jerk, Achilles and Babinski reflexes.

Anatomy of the GI Tract:
The tract runs from mouth to anus and is organised in sequence as follows: the mouth (teeth, tongue and salivary glands), pharynx, oesophagus (25 cm), stomach, small intestine (6 m; duodenum, jejunum and ileum) and large intestine (1.5 m; caecum, colon, rectum and anal canal).
The wall of the tract has four layers, listed from outside inwards as the serosa, muscularis externa (longitudinal and circular), submucosa and mucosa.
The accessory organs are the salivary glands, liver, gall bladder and pancreas.

Anatomy of the Stomach:
The stomach is a J-shaped muscular sac between the oesophagus and duodenum with a capacity of 1 – 1.5 L. Its regions are the cardia, fundus 🔊, body and pylorus 🔊 (with the pyloric sphincter).
In addition to the usual gut-wall layers, it has a third oblique layer of muscle and internal folds called rugae.
The gastric glands contain six specialised cell types.
Parietal (oxyntic) cells 🔊 secrete HCl and intrinsic factor (required for vitamin B₁₂ absorption).
Chief (peptic) cells secrete inactive pepsinogen.
Mucous surface cells secrete mucus and HCO₃⁻, which protect the mucosa.
G cells of the pyloric antrum secrete the hormone gastrin.
Enterochromaffin-like cells secrete histamine, and D cells secrete somatostatin.

Production of Gastric Acid:
The parietal cell uses an H⁺/K⁺ ATPase (proton pump) that exchanges cytoplasmic H⁺ for luminal K⁺, secreting HCl into the gastric lumen (pH 1 – 2).
CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻  (catalysed by carbonic anhydrase) The H⁺ is pumped into the lumen, while HCO₃⁻ leaves across the basolateral membrane in exchange for Cl⁻, producing a post-prandial alkaline tide in the venous blood. About 2 – 3 L of HCl is produced per day.

Regulation of Acid Secretion (Three Phases):
(1) Cephalic phase: sight, smell and taste activate the parasympathetic vagus nerve (CN X), which releases acetylcholine that acts on M₃ receptors of parietal cells and also stimulates gastrin and histamine release.
(2) Gastric phase: stretch and the peptides in chyme stimulate G cells to release gastrin, which acts directly on parietal cells and through histamine released from ECL cells.
(3) Intestinal phase: a brief initial excitation when chyme enters the duodenum is followed by inhibition mediated by secretin, CCK and GIP.
Three stimuli converge on the parietal cell receptors: ACh (M₃), gastrin (CCK-B) and histamine (H₂); activation of cAMP and Ca²⁺ turns on the H⁺/K⁺ ATPase.
Drugs that reduce acid secretion include M₁ blockers (pirenzepine), H₂-blockers (ranitidine, famotidine) and proton-pump inhibitors (omeprazole), which irreversibly block the H⁺/K⁺ ATPase.

Pepsin in Protein Digestion:
Chief cells secrete inactive pepsinogen, which is converted to active pepsin by gastric HCl at pH < 2; the reaction is autocatalytic, as newly formed pepsin activates more pepsinogen. Pepsin is an endopeptidase that cleaves peptide bonds adjacent to aromatic amino acids (phenylalanine, tyrosine and tryptophan), converting proteins into polypeptides and smaller peptides. Its optimum pH is 1.5 – 2.5, and it is irreversibly inactivated above pH 5. Digestion then continues in the duodenum under the action of pancreatic trypsin and chymotrypsin.

Salivary Glands:
There are three major pairs of salivary glands.
The parotid gland 🔊 is the largest, lies anterior to the ear, opens by Stensen's duct opposite the second upper molar, and secretes a mostly serous fluid under parasympathetic control from CN IX.
The submandibular gland 🔊 lies under the jaw, produces a mixed serous and mucous secretion through Wharton's duct, and is innervated by CN VII.
The sublingual gland 🔊 is the smallest, lies beneath the tongue and is mostly mucous, with CN VII innervation.
Numerous minor buccal and lingual glands also exist.
About 1 – 1.5 L of saliva is produced per day at pH 6.2 – 7.6; it is 99.5 % water and contains α-amylase (ptyalin), lingual lipase, mucin, lysozyme, secretory IgA, bicarbonate and electrolytes.
Saliva moistens food for bolus formation, begins starch digestion, lubricates swallowing, cleanses the mouth, has antibacterial action (lysozyme and IgA), dissolves taste stimuli and lubricates speech.

The Pancreas:
The pancreas is a retroperitoneal, mixed exocrine and endocrine gland, about 12 – 15 cm long, that lies behind the stomach.
The exocrine portion (about 98 % of the gland) consists of acinar cells that secrete digestive enzymes, together with duct cells that secrete a bicarbonate-rich alkaline fluid under the control of secretin. The total daily pancreatic juice is about 1500 mL.
The enzymes secreted include inactive proteases — trypsinogen, chymotrypsinogen and procarboxypeptidase. Trypsinogen is activated by intestinal enterokinase to trypsin, which in turn activates the other proteases. Pancreatic amylase digests starch, pancreatic lipase digests triglycerides, and the nucleases DNase and RNase hydrolyse nucleic acids. Enzyme release is stimulated by CCK released from duodenal I cells when fat and protein enter the duodenum.
The endocrine portion (about 2 %) consists of the islets of Langerhans 🔊. The α-cells secrete glucagon (raises blood glucose), the β-cells secrete insulin (lowers blood glucose), the δ-cells secrete somatostatin, and the PP-cells secrete pancreatic polypeptide.

The Liver:
The liver is the largest gland in the body (about 1.5 kg) and lies in the right hypochondrium. It has four lobes — right, left, caudate and quadrate. Its functional unit is the liver lobule, a hexagonal structure with a central vein and three portal triads at its corners, each triad containing a branch of the hepatic artery, the portal vein and a bile duct. Kupffer cells 🔊 line the sinusoids and act as phagocytes.
The liver has a dual blood supply: the hepatic artery (about 30 %, oxygen-rich) and the portal vein (about 70 %, nutrient-rich from the gut).
The principal functions of the liver are the following. It handles carbohydrate metabolism through glycogen storage, glycogenolysis and gluconeogenesis. In protein metabolism it synthesises plasma proteins (albumin and clotting factors) and converts toxic ammonia into urea. In fat metabolism it carries out β-oxidation, ketogenesis, and the synthesis of lipoproteins and cholesterol. It produces about 700 mL of bile per day, which emulsifies dietary fats. It performs detoxification of drugs (through CYP450), hormones and toxins in phase-I and phase-II reactions. It stores vitamins A, D, E, K and B₁₂, and the minerals iron and copper. It synthesises clotting factors I, II, V, VII, IX and X. It is a site of fetal haematopoiesis (from the second to seventh month of gestation). It is a major source of body heat, and its Kupffer cells remove aged red blood cells from the circulation.

Anatomy of the Respiratory System:
The respiratory system is anatomically divided into an upper conducting zone and a lower zone that includes both conducting and respiratory parts.
The upper (conducting) zone comprises the nose, the nasal cavity with its turbinates, the pharynx (divided into the naso-, oro- and laryngopharynx), and the larynx 🔊, which contains the epiglottis and vocal cords.
The lower zone comprises the trachea (about 10 cm long, supported by 16 – 20 C-shaped rings of cartilage), the primary, secondary and tertiary bronchi, and the bronchioles. The bronchioles have no cartilage and branch into terminal and then respiratory bronchioles, alveolar ducts, alveolar sacs and finally the alveoli 🔊 (about 300 million in total), which are the sites of gas exchange.
The lungs are paired organs; the right lung has three lobes and the left has two (because of the cardiac notch). They are covered by the visceral and parietal pleura 🔊 with a thin film of pleural fluid in between.
The alveolar wall contains Type I pneumocytes (which form most of the gas-exchange surface) and Type II pneumocytes, which secrete surfactant 🔊, a lipoprotein rich in dipalmitoyl phosphatidylcholine that lowers alveolar surface tension and prevents alveolar collapse.

Mechanism of Respiration:
Breathing has two phases and occurs at 12 – 18 cycles per minute at rest.
Inspiration is the active phase. The diaphragm contracts and flattens, increasing the vertical diameter of the thorax. The external intercostal muscles contract, raising the ribs and increasing the anteroposterior and transverse diameters. The resulting increase in thoracic volume lowers the intrapulmonary pressure to about 1 mmHg below atmospheric (Boyle's law), and air flows in down the pressure gradient.
Expiration is passive at rest. The diaphragm and external intercostals relax, and the elastic recoil of the lungs and chest wall together with surface tension decrease the thoracic volume. The intrapulmonary pressure rises to about 1 mmHg above atmospheric and air flows out.
During forced expiration the abdominal muscles and internal intercostals contract. The intrapleural pressure remains negative (−4 to −7 mmHg) throughout the cycle, which keeps the lungs adherent to the chest wall.

Regulation of Respiration:
Respiration is regulated by three broad mechanisms.
Neural control arises from the medullary respiratory centres — the DRG generates quiet inspiration and the VRG drives forced inspiration and expiration — together with the pontine pneumotaxic centre (which limits inspiration) and apneustic centre (which prolongs inspiration). The Hering–Breuer reflex from pulmonary stretch receptors inhibits further inspiration when the lungs are over-distended.
Chemical control is mediated by central chemoreceptors in the medulla that respond to CSF H⁺ and PCO₂ (the most powerful drive) and by peripheral chemoreceptors in the carotid and aortic bodies that respond to falls in PaO₂ (below about 60 mmHg), rises in PaCO₂ and falls in arterial pH.
Higher-centre control comes from the cerebral cortex (voluntary control), the hypothalamus (emotion and temperature) and the limbic system.

Lung Volumes (Measured Directly by Spirometry):
The four basic lung volumes are as follows.
The tidal volume (TV) is the volume of air taken in or expelled during a normal quiet breath and is about 500 mL.
The inspiratory reserve volume (IRV) is the additional air that can be inspired beyond a quiet inspiration and is about 3000 mL.
The expiratory reserve volume (ERV) is the additional air that can be forcibly expelled after a quiet expiration and is about 1100 mL.
The residual volume (RV) is the air that remains in the lungs after a maximal expiration and is about 1200 mL; it cannot be measured by spirometry.

Lung Capacities (Sums of Two or More Volumes):
The inspiratory capacity (IC) is TV + IRV = 3500 mL.
The FRC is ERV + RV = 2300 mL.
The vital capacity (VC) is TV + IRV + ERV = 4600 mL (the maximum air that can be moved in one respiratory effort).
The TLC is VC + RV = 5800 mL.
The dynamic tests of pulmonary function include FEV₁, FVC, the FEV₁ / FVC ratio, and PEFR.

Transport of Oxygen:
Oxygen is carried in the blood in two forms.
About 1.5 % is dissolved in plasma (approximately 0.3 mL per 100 mL), obeying Henry's law.
About 98.5 % is chemically bound to haemoglobin as oxyhaemoglobin 🔊. Each haemoglobin molecule binds four oxygen molecules.
One gram of haemoglobin carries 1.34 mL of oxygen, so 100 mL of blood with 15 g of haemoglobin carries about 20 mL of oxygen.
The oxygen–haemoglobin dissociation curve is sigmoidal, with a P₅₀ of about 26 mmHg.
The curve shifts to the right (decreased affinity, increased release of oxygen to the tissues) with rising temperature, rising 2,3-BPG, rising CO₂ and falling pH (the Bohr effect).
It shifts to the left (increased affinity) in the presence of fetal haemoglobin, alkalosis and carbon monoxide poisoning.

Transport of Carbon Dioxide:
CO₂ produced in the tissues is transported to the lungs in three forms.
About 7 % is carried dissolved in the plasma (CO₂ is more soluble than oxygen).
About 23 % is carried as carbamino-haemoglobin, formed by binding of CO₂ to amino groups on the globin chains.
About 70 % is carried as bicarbonate. Inside the red cell, CO₂ reacts with water under the action of carbonic anhydrase to form H₂CO₃, which dissociates into H⁺ and HCO₃⁻; the bicarbonate then leaves the red cell in exchange for Cl⁻ (the chloride shift or Hamburger's shift).
CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻ The H⁺ is buffered by haemoglobin, and the whole process is reversed in the lungs.
According to the Haldane effect, deoxygenated blood carries more CO₂ than oxygenated blood.

Anatomy of the Kidney:
Each kidney is bean-shaped, measuring approximately 12 cm × 6 cm × 3 cm and weighing about 150 g. It lies retroperitoneally at the T12 – L3 vertebral level, with the right kidney slightly lower than the left because of the overlying liver.
Externally, the kidney is enclosed by a fibrous capsule, which is surrounded by perirenal fat and the renal fascia.
Internally, the outer cortex contains the glomeruli and the convoluted tubules, while the inner medulla contains 8 – 18 renal pyramids whose apices (papillae) project into the minor calyces. The minor calyces unite to form major calyces, which open into the renal pelvis that continues as the ureter.
The blood supply begins with the renal artery (about 1100 mL/min, 20 % of the cardiac output); it subdivides into segmental, interlobar, arcuate and interlobular branches, and then gives rise to the afferent arteriole, the glomerulus, the efferent arteriole, the peritubular capillaries or vasa recta, the interlobular veins and finally the renal vein.

The Nephron:
Each kidney contains about one million nephrons. About 85 % are cortical (short-looped) and 15 % are juxtamedullary (long-looped), the latter being responsible for the medullary osmotic gradient.
The parts of the nephron are Bowman's capsule together with its glomerulus (the renal corpuscle, site of filtration), the PCT, the loop of Henle (with descending thin and ascending thick limbs), the DCT and the CD.
The juxtaglomerular apparatus consists of the renin-secreting JG cells of the afferent arteriole and the macula densa in the DCT, which senses tubular NaCl.

Urine Formation — Three Processes:
1. Glomerular filtration. The glomerular hydrostatic pressure drives plasma water and small solutes through a three-layered filtration barrier consisting of fenestrated endothelium, the glomerular basement membrane and podocyte slit diaphragms. The GFR is about 125 mL/min, or 180 L/day. It is determined by afferent and efferent arteriolar tone, the glomerular hydrostatic pressure and the plasma colloid osmotic pressure. Autoregulation keeps GFR constant between a mean arterial pressure of 80 and 180 mmHg.

2. Tubular reabsorption. About 99 % of the filtered water is reabsorbed, so that only 1 – 2 L of urine is produced per day. The PCT reabsorbs 65 % of Na⁺ and water, all of the filtered glucose and amino acids, and most of the HCO₃⁻, K⁺ and Ca²⁺. The descending loop of Henle reabsorbs water while the ascending limb reabsorbs NaCl (the countercurrent multiplier). The DCT reabsorbs Na⁺ and Ca²⁺ (the latter under parathyroid-hormone control). The CD reabsorbs water under ADH (by insertion of aquaporin-2 channels) and exchanges Na⁺ for K⁺ under aldosterone.

3. Tubular secretion. Tubular cells actively secrete H⁺, K⁺, NH₄⁺ and a range of organic acids and drugs (such as penicillins and PAH) into the tubular lumen for excretion.

Role of the Renin–Angiotensin System (RAS):
The RAS is triggered by a fall in blood pressure, decreased renal perfusion, increased sympathetic outflow or a fall in NaCl delivery to the macula densa.
Angiotensinogen → (renin) → Angiotensin I → (ACE, lung) → Angiotensin II Angiotensin II has several actions: it is a potent systemic vasoconstrictor that raises blood pressure, it constricts the efferent arteriole more than the afferent (maintaining GFR in hypotension), it stimulates aldosterone release from the adrenal cortex (promoting Na⁺ and water reabsorption in the collecting duct), it stimulates ADH release from the posterior pituitary, and it stimulates thirst.
The main drug targets are ACE inhibitors (enalapril), angiotensin receptor blockers (ARBs such as losartan) and the renin inhibitor aliskiren.

Classification of Hormones:
Hormones are classified both by chemical nature and by their location of action.
By chemical nature:
(1) Peptide or protein hormones such as insulin, glucagon, growth hormone, ADH, FSH, LH and oxytocin.
(2) Amino-acid derivatives such as thyroxine (T₄ and T₃), the catecholamines adrenaline and noradrenaline, and melatonin.
(3) Steroid hormones derived from cholesterol, including cortisol, aldosterone, oestrogen, progesterone and testosterone.
(4) Eicosanoids 🔊 derived from arachidonic acid, including prostaglandins, thromboxanes and leukotrienes.

By location of action:
Endocrine hormones travel in the blood; paracrine signals act on nearby cells; and autocrine signals act on the cell that released them.

Mechanism of Hormone Action:
Hormones act through two main mechanisms.
Water-soluble hormones (peptides and catecholamines) cannot cross the cell membrane, so they bind a G-protein coupled receptor on the cell surface; this activates second messengers such as cAMP, IP₃, DAG or Ca²⁺, which in turn activate protein kinases and produce a rapid (seconds) cellular response.
Lipid-soluble hormones (steroids and thyroid hormones) diffuse through the membrane and bind an intracellular receptor; the hormone–receptor complex enters the nucleus, binds a hormone response element on DNA, and stimulates transcription and new protein synthesis, giving a slow (hours to days) response.

Structure of the Pituitary Gland:
The pituitary is pea-sized (0.5 g) and is suspended from the hypothalamus by the infundibulum (pituitary stalk), sitting inside the sella turcica of the sphenoid bone.
It has two lobes with different embryological origins. The adenohypophysis (anterior lobe) is glandular, derived from Rathke's pouch of the oral ectoderm, and is connected to the hypothalamus by the hypothalamo-hypophyseal portal system. The neurohypophysis (posterior lobe) is a direct neural extension of the hypothalamus.

Anterior Pituitary Hormones (Six):
Four are tropic and target other endocrine glands.
TSH stimulates release of T₃ and T₄ by the thyroid; ACTH stimulates the adrenal cortex to secrete cortisol; and FSH together with LH act on the gonads.
The non-tropic anterior hormones are GH, which stimulates growth (via IGF-1); PRL (prolactin), which stimulates milk production; and MSH, which stimulates melanogenesis.

Posterior Pituitary Hormones (Stored, Made in the Hypothalamus):
ADH (vasopressin) acts on the collecting duct to insert aquaporin-2 channels, increasing water reabsorption, and causes vasoconstriction; deficiency produces diabetes insipidus.
Oxytocin 🔊 causes uterine contraction during labour and milk ejection during breastfeeding.

Disorders of the Pituitary:
Hypopituitarism, as in Sheehan's syndrome 🔊, occurs after postpartum pituitary infarction.
GH excess produces gigantism in children and acromegaly 🔊 in adults; GH deficiency produces dwarfism.
ADH deficiency causes diabetes insipidus with polyuria up to 20 L/day, while SIADH produces hyponatraemia.
A prolactinoma produces amenorrhoea and galactorrhoea.

1. Thyroid Gland:
Structure: the thyroid is butterfly-shaped, with two lobes connected by an isthmus, lies below the larynx at the C5 – T1 level, weighs 20 – 30 g and has a rich blood supply. Its functional unit is the thyroid follicle, which is filled with colloid and lined by follicular cells.
Hormones: thyroxine (T₄) 🔊 represents about 90 % of thyroid output and is a prohormone, while tri-iodothyronine (T₃) is the biologically active form, about five times more potent and generated in the tissues. Calcitonin 🔊 is secreted by the parafollicular C cells and lowers blood calcium, opposing the action of PTH.
Synthesis of thyroid hormones requires iodine: the iodide trap (Na⁺/I⁻ symporter) concentrates iodide from blood; iodide is oxidised and attached to tyrosine residues of thyroglobulin (forming MIT and DIT); two DITs couple to form T₄ and one MIT + one DIT form T₃; the hormones are stored in the colloid and released on TSH signalling.
Actions: thyroid hormones increase the basal metabolic rate, promote heat production, support growth and central nervous system development (lack in the fetus produces cretinism), and have a positive chronotropic effect on the heart.
Disorders: hyperthyroidism (as in Graves' disease or toxic goitre) produces weight loss, heat intolerance, tachycardia and exophthalmos; hypothyroidism (as in Hashimoto's thyroiditis or myxoedema) produces weight gain, cold intolerance, bradycardia, goitre and constipation; cretinism 🔊 is congenital hypothyroidism with dwarfism and mental retardation; and endemic goitre is due to iodine deficiency.

2. Parathyroid Gland:
Structure: four small pea-sized glands lie on the posterior surface of the thyroid lobes and contain chief cells (which secrete PTH) and oxyphil cells.
Hormone: parathyroid hormone (PTH).
Actions of PTH (all raise blood Ca²⁺): on bone it activates osteoclasts to release Ca²⁺ and phosphate; on kidney it increases Ca²⁺ reabsorption at the distal tubule, decreases phosphate reabsorption and activates vitamin D; and on the intestine, acting through vitamin D, it increases Ca²⁺ absorption.
Secretion of PTH is controlled by the plasma Ca²⁺ level (low calcium increases PTH release).
Disorders: hyperparathyroidism raises Ca²⁺ and produces kidney stones, bone pain and abdominal groans; hypoparathyroidism lowers Ca²⁺ and produces tetany with carpopedal spasm, and the clinical Chvostek 🔊 and Trousseau 🔊 signs.

3. Adrenal Gland:
Structure: the adrenal is a pyramidal gland on top of each kidney and has two functionally distinct parts.
The cortex has three zones, conveniently remembered by the mnemonic "GFR".
The zona glomerulosa secretes the mineralocorticoid aldosterone, which promotes renal Na⁺ and water retention and K⁺ excretion.
The zona fasciculata secretes the glucocorticoid cortisol, which drives gluconeogenesis and has anti-inflammatory and immunosuppressive effects.
The zona reticularis secretes the adrenal androgens, mainly DHEA.
The medulla is a modified sympathetic ganglion; its chromaffin cells secrete adrenaline (about 80 %) and noradrenaline (about 20 %), the hormones of the fight-or-flight response.
Disorders: Cushing's syndrome 🔊 is caused by cortisol excess; Addison's disease 🔊 is primary adrenocortical failure with hyperpigmentation, hyponatraemia, hyperkalaemia and weight loss; Conn's syndrome is primary hyperaldosteronism with hypertension and hypokalaemia; and phaeochromocytoma 🔊 is a catecholamine-secreting tumour of the medulla producing episodic hypertension, palpitations and headache.

1. Endocrine Pancreas:
The endocrine pancreas consists of about one million islets of Langerhans scattered throughout the exocrine tissue. It contains four main cell types.
The β-cells (about 70 %) secrete insulin 🔊, which lowers blood glucose by stimulating GLUT-4-mediated glucose uptake by muscle and adipose tissue, hepatic glycogenesis, lipogenesis and protein synthesis; it is released when blood glucose exceeds about 100 mg/dL.
The α-cells (about 20 %) secrete glucagon, which raises blood glucose by driving hepatic glycogenolysis and gluconeogenesis.
The δ-cells (5 – 10 %) secrete somatostatin, which inhibits the release of insulin, glucagon and growth hormone.
The PP-cells secrete pancreatic polypeptide, which inhibits pancreatic exocrine secretion.
Disorders: in Type 1 diabetes mellitus there is autoimmune β-cell destruction with absolute insulin deficiency, typically presenting in children and young adults and requiring insulin replacement. In Type 2 diabetes mellitus there is insulin resistance with relative deficiency, typically in older or obese adults, managed by diet, exercise and oral hypoglycaemic agents. The classic features are polyuria, polydipsia, polyphagia, weight loss, hyperglycaemia and glycosuria, with ketoacidosis in Type 1.

2. Pineal Gland:
The pineal gland is a pea-sized structure in the epithalamus behind the third ventricle and is composed mainly of pinealocytes.
Its principal hormone is melatonin 🔊, synthesised from serotonin and secreted mostly at night in response to darkness through the retinohypothalamic pathway and the SCN.
Melatonin regulates the circadian rhythm (sleep-wake cycle), acts as an antioxidant, modulates reproductive hormones (more strongly in animals than in humans) and contributes to seasonal biology.
Disorders: a pineal tumour can cause precocious or delayed puberty depending on its effect on melatonin; calcification of the pineal is a normal age-related finding and is used as a radiological landmark.

3. Thymus:
The thymus is a bilobed lymphoid organ in the superior mediastinum behind the sternum; it is largest at puberty and then involutes with age.
Its hormones are thymosin, thymopoietin and thymulin.
The thymus serves as the primary lymphoid organ for T-lymphocyte maturation, in which naïve precursors differentiate into CD4 and CD8 T cells. It is essential for the development of immune tolerance through positive and negative selection in the cortex and medulla, and it also secretes the thymic hormones.
Disorders: DiGeorge syndrome 🔊 is congenital thymic aplasia producing T-cell deficiency; myasthenia gravis 🔊 is an autoimmune disorder with anti-acetylcholine-receptor antibodies at the neuromuscular junction and is associated with thymic hyperplasia or thymoma; and thymoma is a tumour of the thymic epithelium.

Male Reproductive System:
The testes 🔊 lie in the scrotum at about 2 – 3 °C below core body temperature and contain the seminiferous tubules (where spermatogenesis occurs), the Leydig cells (which secrete testosterone) and the Sertoli cells (which nourish developing sperm).
The duct system runs from the epididymis (where sperm are stored and matured) to the vas deferens, the ejaculatory duct and the urethra.
The accessory glands are the seminal vesicles (which contribute a fructose-rich fluid making up about 60 % of semen), the prostate gland 🔊 (which contributes enzymes and citric acid, about 30 % of semen), and the bulbourethral (Cowper's) glands (which add mucus for lubrication).
The penis contains the paired corpora cavernosa, the corpus spongiosum and the urethra.
Semen volume is 2 – 5 mL per ejaculate with a sperm count of 50 – 150 million/mL and a pH of 7.2 – 7.8.
Functions of the male system are the production of sperm, the secretion of testosterone, and the transport and delivery of sperm.

Female Reproductive System:
The ovaries are paired almond-shaped organs that produce oocytes and secrete oestrogen and progesterone.
The fallopian tubes 🔊 consist of the fimbriae, infundibulum, ampulla (where fertilisation normally occurs), isthmus and interstitial portion.
The uterus 🔊 is a pear-shaped organ with a fundus, body and cervix, and its wall has three layers — the outer perimetrium, middle myometrium and inner endometrium.
The vagina is a muscular canal that serves as the organ of copulation, the birth canal and the route of menstrual outflow.
The external genitalia (vulva) include the mons pubis, labia majora and minora, clitoris and vestibule, and the mammary glands produce milk after parturition.
Functions of the female system are oocyte production, fertilisation, pregnancy, parturition, lactation and sex-hormone secretion.

Sex Hormones:
Male hormone: testosterone 🔊 is produced by Leydig cells from cholesterol; it promotes spermatogenesis, develops secondary sexual characters (deep voice, facial hair, muscle bulk), sustains libido and has an anabolic effect. It is regulated by the HPG axis — hypothalamic GnRH stimulates pituitary FSH and LH, which act on Sertoli and Leydig cells respectively, with negative feedback by testosterone and inhibin.
Female hormones: Oestrogen (estradiol) 🔊 is produced by granulosa cells and drives follicular development, endometrial proliferation, secondary sexual characters and, by positive feedback, the mid-cycle LH surge. Progesterone is produced by the corpus luteum and placenta, maintains the secretory endometrium, keeps the uterus quiescent in pregnancy and promotes mammary development. The ovary and adrenal also produce small amounts of testosterone. hCG from the placenta rescues the corpus luteum in early pregnancy and is the basis of the pregnancy test. Relaxin softens the cervix and pelvic ligaments, and prolactin together with oxytocin support lactation.

Menstrual Cycle (28 Days, Three Phases):
Menstrual phase (days 1 – 5): the endometrium sheds, with a loss of about 50 mL of blood, because of falling progesterone and oestrogen from the regressing corpus luteum.
Follicular (proliferative) phase (days 6 – 14): FSH stimulates follicular maturation from primordial to Graafian follicle; granulosa cells secrete oestrogen, which drives endometrial proliferation; the oestrogen peak on day 12 – 13 triggers an LH surge by positive feedback; and the Graafian follicle ruptures at ovulation on about day 14, releasing the oocyte.
Luteal (secretory) phase (days 15 – 28): the ruptured follicle forms the corpus luteum, which secretes progesterone and oestrogen; the endometrium becomes secretory (with coiled glands rich in glycogen); if no fertilisation occurs, the corpus luteum regresses around day 26 and the hormones fall, leading to menstruation; if fertilisation does occur, hCG from the implanting embryo rescues the corpus luteum.

Fertilisation:
Fertilisation normally takes place in the ampulla of the fallopian tube within about 24 hours of ovulation.
The steps are as follows. (1) Sperm swim through the cervix, uterus and fallopian tube; of about 300 million ejaculated, only a few hundred reach the ampulla. (2) Capacitation 🔊 modifies the sperm plasma membrane so that it can penetrate the oocyte. (3) The sperm binds the zona pellucida receptor ZP3. (4) The acrosome reaction releases hyaluronidase and acrosin, which dissolve the zona pellucida. (5) The sperm head enters the ovum, triggering the cortical reaction that hardens the zona and blocks polyspermy. (6) The male and female pronuclei fuse to form a diploid zygote (46 XX or 46 XY). (7) Rapid mitotic divisions produce a 2-, 4-, 8- and 16-cell morula, then a blastocyst, which implants in the uterine endometrium on day 6 – 7.

Spermatogenesis:
Spermatogenesis occurs continuously in the seminiferous tubules and takes about 64 – 72 days.
The sequence is: spermatogonium (2n) → primary spermatocyte (2n) → meiosis I → two secondary spermatocytes (n) → meiosis II → four spermatids (n) → spermiogenesis 🔊 → four mature spermatozoa.
The process is supported by Sertoli cells (forming the blood-testis barrier and providing nutrition) and is controlled by FSH and testosterone.
A mature spermatozoon has a head (nucleus + acrosome), a midpiece (mitochondria) and a tail (flagellum).

Oogenesis:
Oogenesis begins in fetal life and is completed only at fertilisation.
The sequence is: oogonium (fetal) → primary oocyte (arrested at prophase I until puberty) → at each cycle, one oocyte resumes meiosis I → secondary oocyte with the first polar body (n) → arrests at metaphase II → is ovulated → meiosis II is completed only if fertilisation occurs, producing the ovum and a second polar body.
Each oogonium therefore gives rise to one ovum and three polar bodies (compared with four sperm from spermatogenesis). The process is regulated by FSH, LH, oestrogen and progesterone.

Digestion and Absorption:
Carbohydrates are digested by salivary and pancreatic amylases to disaccharides, which are further broken down by brush-border enzymes (maltase, sucrase and lactase) to the monosaccharides glucose, fructose and galactose. Glucose and galactose are absorbed by the Na⁺-dependent SGLT-1, while fructose uses GLUT-5.
Proteins are digested in the stomach by pepsin and in the small intestine by pancreatic trypsin, chymotrypsin and carboxypeptidase to peptides, which brush-border peptidases further reduce to amino acids absorbed by Na⁺-coupled transporters.
Fats are emulsified by bile salts and hydrolysed by pancreatic lipase to monoglycerides and fatty acids, which form micelles with bile salts and diffuse into the enterocyte. Inside the enterocyte they are re-esterified to triglycerides and packaged as chylomicrons, which enter the lymphatic lacteals and reach the bloodstream through the thoracic duct.
Vitamins, water and electrolytes are absorbed by various mechanisms: the fat-soluble vitamins (A, D, E and K) travel with lipids, the water-soluble vitamins by active transport, iron and calcium are actively absorbed in the duodenum, and vitamin B₁₂ is absorbed only in the ileum after binding intrinsic factor.

Energetics:
The hydrolysis of the terminal phosphate bond of ATP releases about 7.3 kcal/mol, and most of the cell's ATP is produced in the mitochondria by oxidative phosphorylation; one molecule of glucose yields approximately 36 molecules of ATP by complete oxidation.
Creatine phosphate 🔊 is the rapid phosphate reserve of muscle; it transfers phosphate to ADP to form ATP during the first ten seconds of intense exercise.
The basal metabolic rate (BMR) is the baseline energy expenditure at complete rest, after 12 hours of fasting, in a thermoneutral environment; the normal value is 35 – 40 kcal/m²/h in men and 33 – 37 kcal/m²/h in women, giving a total of about 1500 – 1800 kcal/day in men and 1200 – 1500 kcal/day in women.
BMR is increased by a larger body surface area, thyroxine, adrenaline, fever (by about 13 % per °C), pregnancy and lactation; it is decreased with advancing age, during starvation and during sleep. Men have a higher BMR than women because of a greater muscle mass.

Chromosomes, Genes and DNA:
Chromosomes 🔊 are structures of condensed DNA and histone proteins in the cell nucleus; each human somatic cell contains 46 chromosomes (23 pairs), comprising 22 pairs of autosomes and one pair of sex chromosomes (XX in females and XY in males).
A gene is a segment of DNA that codes for a specific polypeptide or a functional RNA.
DNA is a double helix (Watson and Crick, 1953) whose backbone is made of deoxyribose sugar and phosphate; it contains four bases — adenine, thymine, guanine and cytosine — with A – T pairing through two hydrogen bonds and G – C through three.
RNA 🔊 is single-stranded, contains the ribose sugar, and has uracil in place of thymine; its three main forms are mRNA, tRNA and rRNA.

Protein Synthesis (Central Dogma):
The central dogma of molecular biology is DNA → mRNA → protein.
(1) In transcription (in the nucleus), RNA polymerase reads the DNA template and synthesises a complementary mRNA strand.
(2) The mRNA is then processed by splicing, 5′ capping and 3′ polyadenylation.
(3) The mature mRNA is exported to the cytoplasm and attaches to a ribosome.
(4) In translation, tRNA molecules bring amino acids in order, each three-base codon specifying a single amino acid, while the ribosome assembles the polypeptide through initiation, elongation and termination.
(5) The newly synthesised polypeptide is folded and post-translationally modified to become a functional protein.
The genetic code comprises 64 codons: 61 code for the 20 amino acids (making the code degenerate), three are stop codons (UAA, UAG and UGA) and one (AUG, methionine) is the start codon.

Patterns of Inheritance (Mendelian and Others):
Autosomal dominant conditions require only one mutant allele, affect both sexes equally, and appear in every generation; examples include Huntington's disease, Marfan's syndrome and achondroplasia.
Autosomal recessive conditions require two mutant alleles, tend to skip generations and often appear in consanguineous families; examples include cystic fibrosis, sickle-cell disease, phenylketonuria and thalassaemia.
X-linked recessive conditions primarily affect males (females being usually carriers); examples are haemophilia A and B, Duchenne muscular dystrophy, G6PD deficiency and red-green colour blindness.
X-linked dominant conditions are rare and include vitamin-D-resistant rickets.
Mitochondrial inheritance is always maternal, since only the ovum contributes mitochondria; examples are MELAS and Leber's hereditary optic neuropathy.
Polygenic (multifactorial) conditions arise from the combined effect of many genes together with environment; examples include diabetes, hypertension and schizophrenia.