Allosteric and hormonal regulation of metabolic pathways

Glycolysis and pyruvate oxidation

• Hexokinase Glucose-6-phosphate (-)
• Glucokinase (No end-product inhibition) Insulin (+)
• PFK-1 Fructose 2,6-BP, AMP (+); citrate (-) Glucagon (-)
• Pyruvate kinase Fructose 1,6-BP (+); ATP, alanine (-) Glucagon (-)
• Pyruvate dehydrogenase ADP (+); ATP, acetyl CoA, NADH (-) Insulin (+)

Citric acid cycle

Isocitrate dehydrogenase ADP (+); ATP, NADH (-)

Glycogenesis

Glycogen synthase Glucose 6-phosphate (+)

Insulin (+); glucagon in liver (-), epinephrine in muscle (-)

Gluconeogenesis

Fructose 1,6-biphosphatase Citrate (+); AMP, Fructose 2,6-BP (-) Glucagon (+)

PEP carboxykinase

Pyruvate carboxylase Acetyl CoA (+)

^ All three enzymes induced by glucagon, cortisol; suppressed by insulin

Pentose phosphate pathway

G6PD is inhibited by NADH

Fatty acid synthesis

Acetyl CoA carboxylase Citrate (+); palmitate (-) Insulin (+) Glucagon (-)

Lipolysis

Hormone sensitive lipase Epinephrine (+); insulin (-)

Beta-oxidation of fatty acids

Carnitine acyltransferase Malonyl CoA (-) *a byproduct of fatty acid synthesis, so you can't have both synthesis and beta-oxidation at the same time, futilely

Cholesterol synthesis

HMG CoA reductase Cholesterol (-) Insulin (+); glucagon (-)

Urea cycle

Carbamoyl phosphate synthetase I N-Acetylglutamate (+)

Pyrimidine synthesis

Carbamoyl phosphate synthetase II PRPP, ATP (+), UTP (-)

Purine synthesis

PRPP amidotransferase PRPP (+); IMP, AMP, GMP (-)

Heme synthesis

ALA synthase Heme (-)

Nitrogen metabolism and nucleotide synthesis and metabolism

Tryptophan is the precursor to serotonin, melatonin, and niacin.

Tryptophan ---(tetrahydrobiopterin)--> 5-hydroxytryptophan

5-hydroxytryptophan ---(pyridoxine)-->serotonin

Serotonin ---(SAM)--> melatonin

Serotonin breakdown product: 5-HIAA

Serotonin effects: arteriole vasocontrictor, intestinal peristalsis. Carcinoid syndrome, where serotonin secreting tumor of small intestine metastasizes to liver, has symptoms of cyanotic flushing, low blood pressure (arteriole vasoconstriction), also watery diarrhea (increased peristalsis).

Glutamate --> GABA (decarboxylation)

Histidine --> Histamine (decarboxylation)

Arginine, glycine, and SAM --> creatine.

Creatine --> Creatine phosphate (creatine kinase)

Creatine is a source of high energy phosphate, to regenerate ATP from ADP

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Purines include adenine and guanine (Mnemonic: Pure As Gold)

The pyrimidines are cytosine, thymine, and uracil. Thymine is found only in DNA; uracil, only in RNA.

A nucleotide consists of three components: base, pentose, and phosphate group. A nucleoside is a base and a pentose. Hence, you can call ATP either a nucleotide or a nucleoside triphosphate.

The pentose can be in the deoxy form or the non-deoxy form. The non-deoxy form of the nucleoside DIPHOSPHATE, found in RNA bases, is reduced to the deoxy form by an important enzyme, ribonucleotide reductase. For instance, ADP --> dADP. Reduced thioredoxin is required as a cofactor. In the process, thioredoxin is oxidized. To continue the process, oxidized thioredoxin must be converted to reduced thioredoxin.

Oxidized thioredoxin --> Reduced thioredoxin (NADPH)

Compare: BH2 --> BH4

Ribose 5-phosphate --> PRPP (can now go purine salvage, purine synthesis, pyrimidine synthesis). PRPP synthethase (requires ATP-->AMP) is the rate-limiting enzyme of purine synthesis.

PRPP --> 5-phosphoribosylamine (glutamine --> glutamate) is the committed step of purine synthesis. This is a highly regulated transformation. The end products inhibit: IMP, AMP, GMP. An accumulation of PRPP will enhance.

5-phosphoribosylamine --> IMP in a series of 9 reactions.

IMP is the decision point between AMP and GMP synthesis. Control of relative amounts of each is controlled partly by end-product inhibition (AMP, GMP) respectively as well as cross-regulation (GTP and ATP are required for AMP and GMP synthesis, respectively).

Purine salvage: PRPP conveys ribose 5-phosphate to "salvaged" free bases to form nucleotides.

Nucleoside diphosphates and triphosphates formed from monophosphates by kinase activity utilizing ATP.

Purine ring synthesis happens on the scaffold of the ribose 5-phosphate. On the other hand, synthesis of the pyrimidine ring happens before the ribose 5-phosphate comes in, in the form of PRPP. The defining enzyme of pyrimidine synthesis is carbamoyl phosphate synthetase II (CPS II), which is a cytosolic enzyme (as opposed to the mitochondrial urea cycle enzyme, CPS I; note that CPS II, unlike CPS I, is not activated by N-acetyl glutamate). It catalyzes the formation of carbamoyl phosphate from phosphorylated bicarbonate (CO2, ATP) and an amine group (donated from glutamine --> glutamate). CPS II catalyzes the committed step of pyrimidine synthesis and is inhibited by UTP, activated by ATP.

Addition of aspartate by aspartate transcarbamoylase takes carbamoyl phosphate to carbamoyl aspartate. This step is inhibited by CTP, and activated by ATP. The regulation of the these last two steps represents both end-product inhibition (UTP, CTP) as well as a mechanism to balance synthesis of pyrimidines and purines (ATP activation).

Dihydroorotase takes carbamoyl aspartate to dihydroorotate, which is then oxidized to produce orotic acid, or orotate. Conversion of orotate to UMP requires orotate phosphoribosyl transferase (addition of ribose 5-phosphate from PRPP) and orotidine phosphate decarboxylase. UMP can give rise to dUMP (ribonucleotide reductase) and then dTMP (thymidylate synthase, which uses methylene tetrahydrofolate as the carbon donor to methylate dUMP). UMP goes to UTP (ATP addition x2) before becoming CTP (amine donation from Gln --> Glu).

Methotrexate, fluorouracil, and hydroxyurea are anticancer drugs that work by inhibiting nucleotide synthesis. Methotrexate competitively inhibits dihydrofolate reductase, inhibiting dTMP synthesis and fluorouracil in its activated form (5-fluorodeoxyuridine monophosphate) inhibits thymidylate synthase (irreversible suicide inhibitor) directly, also inhibiting dTMP synthesis.

Purine degradation and salvage. The central pathway is IMP --> Inosine --> Hypoxanthine --> Xanthine --> Uric acid. AMP goes to IMP by AMP deaminase. Adenosine goes to inosine by adenosine deaminase. [*CC] SCID, autosomal recessive. Deficiency of ADA causes this. First effect is accumulation of adenosine, which is toxic to B and T cells. It also leads to accumulation of dAMP, which gets converted to excess dATP, which inhibits ribonucleotide reductase, which reduces conversion of ribonucleotides to deoxyribonucleotides, resulting in decrease in DNA synthesis of B and T cells. SCID leads to recurrent infections with bacteria, viruses, fungi, and protozoa (loss of humoral and cellular immunity). Note that the "A" derivatives dump into the degradation pathway via AMP and adenosine only. The "G" derivatives, on the other hand, dump in with Guanine going to Xanthine. You can have GMP --> Guanosine --> Guanine, with Guanine having the option to not degrade via Xanthine, and instead using HGPRT to reinstate itself as GMP by condensing with PRPP. Similarly AMP can be created by adenine condensing with PRPP via enzyme APRT action. Note however that adenine, unlike guanine, cannot dump into the degradation pathway directly. Hypoxanthine can go to IMP via HGPRT as well. [**CC] If HGPRT is blocked, you get no salvage of hypoxanthine to IMP, or guanine to GMP, and therefore more degradation of hypoxanthine and guanine to xanthine and then uric acid, hence hyperuricemia. Since this is a X-linked recessive condition, you get hyperuricemia during development causing severe mental retardation, self-mutilating behavior, spasticity, gout and urate deposition in the kidney, leading to renal failure, which is what kills you in the first or second decade. Hypoxanthine to xanthine, and xanthine to uric acid, is catalyzed by xanthine oxidase. [**CC] Gout is caused either by overproduction of uric acid (overactivity of PRPP synthetase, or deficiency of HGPRT -- as in Lesch-Nyhan), or undersecretion (renal issue). Acute gout strikes the MP joint of the large toe. Recurrent attacks, hyperuricemia with deposition of monosodium urate crystals in synovial fluid. Tx: Reduce alcohol, red meats, use uricosuric agents like probenecid (blocks OAT, organic anion transporter, hence uptake of uric acid from renal tubules) with undersecreters and allopurinol (xanthine oxidase competitive inhibitor) with overproducers. Colchicine also can be administered; it inhibits urate crystal formation by raising tissue pH (low tissue pH promotes urate crystal formation).

Pyrimidine degradation: beta-amino acids, carbon dioxide, and NH4+. Ultimately the degradation product is urea (from NH4+ degradation).

Note that adenine is salvaged with a separate enzyme (APRT) than hypoxanthine and guanine (HGPRT).

Muscle

What happens when skeletal muscle motor units lose innervation?

A: They atrophy, replaced by connective tissue. Innervation also determines the type of muscle fiber.

Some differences between cardiac muscle and skeletal muscle?

A: Triad of SR-T-tubule-SR in skeletal, diad in cardiac. In skeletal the triad is at the AI junction. In cardiac it is at the Z line, so only one per sarcomere. In cardiac muscle calcium is actively transported into the cell by L-type channels to maintain contraction; this is important in calcium-induced calcium release. In skeletal muscle all calcium derives from the SR in a regenerative process. Skeletal muscle is innervated by somatic motor. Cardiac is spontaneous, with gap junctions, regulated by ANS. Only skeletal muscle has the ability to hypertrophy (hyperplasia as well). Once dead, cardiac muscle does not regenerate (or very little). Skeletal muscle is formed by fusion of myoblasts so it's a long, electrically communicative cylinder. On the other hand, cardiac myocytes are electrically coupled by intercalated discs (fascia adherens (doesn't go all the way around cell so not zonula adherens), desmosomes, gap junctions), but maintain their individuality. Skeletal: nuclei thin, peripherally located. Cardiac: centrally located more round nuclei, with pale staining perinuclear area with mitochondria and glycogen.

Smooth muscle has dense bodies, visceral innervation, can regenerate by mitosis, no striations.

Notes on Baby Moore -- Thorax

Figure 2.9. Transverse section of thorax. Anterior portion of external intercostal muscle is membranous. Posterior portion of internal intercostal muscle is membranous. Anterior portion of innermost intercostal is membranous, but you have transversus thoracis in the same "layer" parasternally. The intercostal blood supply comes from internal thoracic anteriorly (anterior intercostal and anterior perforating branches) and from the aorta posteriorly (posterior branch of posterior intercostal, posterior intercostal, and lateral cutaneous branches). The nerve supply is split at the rami, with posterior rami supplying back, and the ventral rami giving rise to the intercostal nerves, with lateral cutaneous and anterior cutaneous branches.

Thoracic wall muscles that depress the ribs: transversus thoracis, internal intercostals, serratus posterior inferior.

Thoracic wall muscles that elevate the ribs: external intercostals, levator costarum, serratus posterior superior, subcostals, (innermost intercostals).

Muscular branches of intercostal nerves.

1st and 2nd intercostal nerves are atypical: run along internal surface of 1st and 2nd ribs in first part of their course.

Dermatome and myotome strips, T1-T12 down thorax. One single spinal nerve lesion may not be noticeable due to overlap!

Rami communicantes. White ramus is presynaptic sympathetic fiber. Gray ramus is postsynaptic sympathetic fiber, join anterior ramus of nearest spinal nerve, including all intercostal nerves, to be distributed to blood vessels, smooth muscle, sweat glands.

Intercostal needle inserted just superior to rib, but high enough to avoid collateral nerves and vessels.

The sternum correlates with thoracic vertebral levels. Manubrium -- T3-T4. T4/T5 is the sternal angle. T5-T9 is the body of the sternum, with T9 being the xiphisternal joint, where the converging costal margins form the infrasternal angle, at the epigastric fossa. Sternal angle -- branching of trachea. Arch of aorta, SVC deep to manubrium.

Nipple in men is over 4th intercostal space.

Vasculature of thoracic wall. Arteries. Posterior from thoracic aorta. Anterior from subclavian -- superior intercostal, internal thoracic/musculophrenic; axillary -- superior thoracic, lateral thoracic. Posterior = superior intercostal + intercostals. Anterior = internal thoracic/musculophrenic. Venous drainage. Posterior intercostal through azygos on the right, hemi- and accessory azygos on the left. Anterior drainage through internal thoracic. Azygos dumps into SVC.

Right lung is heavier, shorter, wider, doesn't have cardiac notch, or lingula in superior lobe, has both horizontal (between superior and middle lobes), oblique (between middle and inferior lobes), did I mention there were three lobes. The left lung has two lobes: superior, inferior.

Fourth rib is about where the horizontal fissure on right lung is. The oblique fissure extends from about 4th to 6th ribs. In the back, the parietal pleura extend to T12, but lungs only to T10.

Base of lung also refers to inferoposterior costal surface.

Right main bronchus is wider, more vertical, more likely to trap aspirated objects.

Carina is extension of last cartilaginous ring of trachea. Can be distorted, widened posteriorly, immobile if bronchial carcinoma present and migrated to the tracheobronchial lymph nodes.

Lung vasculature. There are intrasegmental veins. Parietal pleural veins drain at points of adjacency to systemic veins. Visceral pleural veins drain to pulmonary veins. Bronchial arteries exist. They arise from thoracic aorta on the left, and variable origin on the right (superior posterior intercostal, or left bronchial artery). These bronchial arteries also supply upper esophagus and anastomose with pulmonary arteries. Venous drainage. Partly through pulmonary veins, partly through azygos system.

Beck's triad for cardiac tamponade. Jugular venous distention, low arterial blood pressure, and muffled heart sounds.

Pericardiacophrenic artery and musculophrenic artery supply pericardium.

Referred pain from phrenic nerves (C3-C5) often appear at ipsilateral supraclavicular region (top of shoulder).

Transverse pericardiac sinus (aorta, pulmonary trunk). Oblique pericardial sinus (pulmonary veins, IVC, SVC).

Mnemonic: Intercostal bundle

VAN (from superior to inferior)

V = Vein

A = Artery

N = Nerve

These run inbetween innermost and internal intercostal muscles, in the costal groove just below each rib.

Mnemonic: thoracoacromial artery

Cadavers are dead people

C = Clavicular
A = Acromial
D = Deltoid
P = Pectoral

Mnemonic: axillary artery

She tastes like sweet apple pie

S = Superior thoracic artery
T = Thoracoacromial artery
L = Lateral thoracic artery
S = Subscapular artery
A = Anterior humeral circumflex artery
P = Posterior humeral circumflex artery

Mnemonic: subclavian artery

VITamin C & D.

V = vertebral
I = internal thoracic (mammary) artery
T = thyrocervical trunk
.....inferior thyroid artery, suprascapular artery, transverse cervical artery

C = costocervical trunk
.....supreme intercostal artery, deep cervical artery
D = dorsal scapular artery

Anatomy VI - internal features of the heart

Pectinate muscles -- "true" atrium, horizontal ridges of muscles on anterior atrial wall

Crista terminalis -- border between true atrium and smooth tissue derived from sinus venosum

Posterior wall of right atrium contains SVC, IVC, coronary sinus, and fossa ovalis and limbus fossa ovalis. There are papillary muscles in the ventricles. In the right ventricle, they connect to the three cusps -- anterior, posterior, and septal -- via the chordae tendineae. The anterior papillary muscle is the largest. The posterior is smaller, and the septal is smallest and may be multiple. Each chordae tendineae connects to two cusps. The inner surface of the right ventricle is roughened by trabeculae carneae. The septomarginal trabecula (moderator band) extends from the anterior papillary muscle base to the interventricular septum. It contains part of the right bundle branch, the part that stimulates the papillary muscles. the conus arteriosus (infundibulum) is the smooth, cone-shaped portion of the ventricle leading to the pulmonary trunk. The pulmonary valve has three semilunar valves: left, right, and anterior. Each valve has one fibrous nodule and two lunules, which keep the valve closed to prevent backflow during diastole.

The left atrium is pretty much in the back of the heart. The four great pulmonary veins enter it. The right pulmonary veins are in line with the SVC and PVC. The left atrium is pretty boring: valve of foramen ovale, left auricle, mitral valve. The left ventricle, like the right ventricle, also contains papillary muscles, including anterior papillary muscle and posterior papillary muscle. There is also chordae tendineae as well as trabeculae carneae. As previously mentioned, the aortic valve consists of left, right, and posterior semilunar cusps. The intraventricular septum has a muscular part coming from the apex, and a membranous part connecting just inferior to the right cusp of the aortic valve. The coronary arteries come out of the aortic sinuses. The posterior cusp is the noncoronary cusp.

The AV node is at the superior end of the crista terminalis in the right atrium, right below the SVC. AV impulses pass in AV bundle through membranous septum, then dividing into right and left bundles, which lie on either side of the muscular septum. Again, the right bundle travels through the septomarginal trabecula.

The distance

"Nobody is capable of really thinking about anyone, even in the worst calamity."

Anatomy V -- external features of the heart

Coronary (atrioventricular) sulcus -- separates atria and ventricles

Anterior (or posterior) interventricular sulcus

Some pretty useless surface terms:

Sternocostal surface (anterior) -- right ventricle

Diaphragmatic surface (inferior) -- left ventricle, small part right ventricle

Pulmonary surface (left) -- left ventricle, forms the cardiac impression on left lung

Right auricle and left auricle -- earlobe like extensions to the atria

The cardiac veins and arteries are located below the visceral pericardium. The veins are superficial to the arteries.

Coronary sinus, dilated, 2-2.5cm in length, opens into right atrium in groove between SVC and tricuspid valve, just above the tricuspid in the right auricle. Coronary sinus runs superiorly in coronary sulcus to receive great cardiac vein, which upon reaching the sternocostal surface runs down the anterior interventricular sulcus. The coronary sinus gives off the middle cardiac vein at the posterior interventricular sulcus. The small cardiac vein runs inferiorly down the coronary groove from the coronary sinus and then left along the inferior border of the heart.

While most veins connect with coronary sinus, the anterior cardiac veins do not. They cross the atrioventricular sulcus, draining the anterior surface of the right ventricle into the right atrium. They are superficial to the right coronary artery.

The aortic valve has three semilunar cusps: left, right, and posterior. Behind each cusp is an aortic sinus (left, right, and posterior). The left aortic sinus gives rise to the left coronary artery, which courses down to split at the junction of the coronary sulcus and interventricular sulcus to form the anterior interventricular branch (left anterior descending artery) and the circumflex branch, which wraps posterior around the coronary sulcus to supply the posterior wall of the left ventricle. The right aortic sinus gives rise to the right coronary artery, which courses down the coronary sulcus around the heart to the diaphragmatic surface. It gives off several tributaries: the anterior right atrial branch, which itself has a sinuatrial nodal branch (spelled correctly) to supply the SA node; the marginal branch, running along with the small cardiac vein along the inferior surface toward, but not reaching, the left ventricle; the artery to the atrioventricular node, on the diaphragmatic surface at the coronary sulcus and interventricular juncture; the posterior interventricular branch, which also comes off at that juncture (in 15% of hearts, comes off the left coronary artery). There are anastomoses between the left circumflex and right coronary artery on the posterior surface, and between the posterior interventricular branch and the left anterior descending artery (anterior interventricular branch) at the apex of the heart.

We all have plague

"We can't stir a finger in this world without the risk of bringing death to somebody. Yes, I've been ashamed ever since; I have realized that we all have plague, and I have lost my peace."

Anatomy IV -- external occipital protuberance, superficial back muscles, triangles

The external occipital protuberance. 3cm inferolaterally in the thick fascia, we have the greater occipital nerve penetrating the trapezius. It innervates the back of the scalp. Laterally to that we find the occipital artery, which supplies the back of scalp, sternocleidomastoid muscles, and other deep muscles of the back and neck.

The skin of the back is thick. Funny story: someone suggested this is an evolutionary adaptation against being backstabbed.

The trapezius is a kite-shaped muscle attaching to the lateral third of clavicle, acromion, and spine of scapula. It can raise, retract, and lower the scapula. It is innervated by the accessory nerve and the ventral rami of C3/C4 spinal nerves. Blood supply: transverse cervical artery (branch of thyrocervical trunk).

The latissimus dorsi muscle attaches proximally to T7-T12, thoracolumbar fascia, iliac crest, ribs 9-12 and distally terminates in intertubercular sulcus of anterior side of humerus. It receives blood and nerve supply from the thoracodorsal artery and nerve.

Rhomboids, major and minor. Minor attaches proximally to nuchal ligament and C7/T1, distally to medial border of scapula at the level of the spine. Major attaches proximally to T2-T5, distally to medial border of scapula below level of the spine. Both rhomboids retract the scapula. They are supplied by dorsal scapular nerve and artery. Dorsal scapular artery may branch directly from subclavian or may be a branch off transverse cervical artery (normal anatomical variation).

Levator scapulae. Proximal attachment: transverse processes of C1-C4. Distal attachment: scapula, superior angle. Dorsal scapular nerve and artery supply it. It elevates scapula and rotates scapula to depress glenoid cavity.

Triangle of auscultation: latissimus dorsi, trapezius (inferior part), rhomboid major. Lung sounds clearly heard here.

Lumbar triangle: latissimus dorsi, external oblique, iliac crest. Floor of lumbar triangle is internal oblique. Can be site of lumbar hernia.

The silence

"I can understand this sort of fervor and find it not displeasing. At the beginning of a pestilence and when it ends, there's always a propensity for rhetoric. In the first case, habits have not yet been lost; in the second, they're returning. It is in the thick of a calamity that one gets hardened to the truth--in other words, to silence."

Anatomy III -- intercostal nerves and arteries

Dorsal and ventral rootlets become the dorsal and ventral roots, which fuse to form the spinal nerve, which then splits into the dorsal and ventral rami. The intercostal nerves derive from T1-T11 (T12 is the subcostal nerve) anterior rami. The intercostal nerve (page 20, Grant's 12e) runs in the groove between the innermost and internal intercostal muscles. The intercostal nerve innervates the intercostal muscles and overlying skin regions. Laterally, it gives off the lateral pectoral cutaneous branch, which itself has branches, including lateral mammary and posterior branches. Anteriorly it gives off the anterior pectoral cutaneous branch, which has branches, including the medial mammary branch. The posterior ramus innervates the deep muscles of the back (i.e. erector spinae) and skin adjacent to vertebra column.

The blood supply is similar. The posterior intercostal artery derives from the aorta, with the posterior branch supplying the back, and the main artery looping around laterally, with a lateral pectoral cutaneous branch, as with the nerve. The anterior supply, however, is distinct and derives from the internal thoracic artery. The anterior intercostal artery runs in the same intercostal groove, while the anterior perforating branch comes through to the skin in the parasternal region.

Lane Pryce channels Mark Twain

"I feel like I just went to my own funeral. I didn't like the eulogy."

Betty Draper clinic in parenting

Bobby: I'm bored.
Betty: Go bang your head against a wall.
Bobby: Mom.
Betty: Only boring people are bored.

Anatomy II -- vertebral column

Anatomy of a thoracic vertebra. Take the body, at 6 o' clock position. Going clockwise, we have pedicle, transverse process, lamina, spinous process, lamina, transverse process, pedicle, now back to body. This ring of bone surrounds the vertebral foramen.

We now examine the articulations. Consider the rib coming out of the T4/T5 juncture. It articulates with the inferior costal facet of T4 and the superior costal facet of T5. As it arches around the back it further articulates with the transverse costal facet of T5. The thoracic vertebra articulate with each other above and below through the superior articular process, which rises above and posteriorly to the pedicle, and the inferior articular process, on the underside of the spinous process, which jets down inferiorly to meet the superior articular process. The superior vertebral notch is above the pedicle, and the inferior vertebral notch is below the pedicle. These unite to form the intervertebral foramen. From the side, the rib obscures the superior vertebral notch. The spinal nerves run through the inferior vertebral notches. Intervertebral discs are between vertebra.

Cervical vertebra differ: the spinous process is shorter and bifurcated, body is smaller, vertebral foramen is larger, there are foramen transversarium. There are no rib articulations. The articular processes are almost horizontal rather than oblique in the case of thoracic vertebra, and the inferior articular process is not located on the underside of the spinous process, but rather on the underside of the vertebra anterior to the lamina. Atlas (C1) has no body. Axis (C2) has a dens, which is the body of C1 that has become fused to C2 during development. Vertebra prominens (C7) has the most prominent spinous process, and is easily palpated on the back of the neck.

Lumbar vertebra differ. They have larger bodies, broad spinous processes that project posteriorly and do not overlap, and do not have transverse costal facets.

The sacrum consists of five fused vertebra with no identifiable spines or transverse processes. On the dorsal surface, there is a median sacral crest, four posterior sacral foramina, and a sacral hiatus. The coccyx is a small triangular bone formed by four rudimentary coccygeal vertebra.

Anatomy I -- mediastinum and lungs

The parietal and visceral pleura meet at the root of the lung. If the pleural cavity is breached, the potential space becomes a real space as the lung collapses due to its intrinsic elastic recoil. Air (pneumothorax) or blood (hemothorax) can then enter this space. A needle can be inserted into the costodiaphragmatic recess to clear any fluid accumulated.

The mediastinum can be divided into superior and inferior divisions. The dividing line intersects the sternal angle (inferior edge of manubrium) and the T4/T5 junction. The inferior division is further subdivided into anterior, middle, and posterior subdivisions. The superior mediastinum contains the big tubes: trachea, esophagus, aorta. The trachea branches into the left and right bronchus at this level. It contains the thymus, which is atrophied in adults. It contains the phrenic nerves, which innervate the diaphragm, as well as the great vessels. The azygos vein and thoracic duct are found here as well. The anterior mediastinum is pretty boring, containing only lymph nodes, fat, connective tissue, and perhaps the inferior edge of the thymus. Heme-oncs look here for lymphomas (both HL and NHL) and other malignant masses. The middle mediastinum contains the heart, pericardium, great vessels, and phrenic nerves. The heart is not directly centered under the sternum but protrudes more to the left. The posterior mediastinum contains the descending aorta, which is quite posterior, behind the esophagus. It also contains the thoracic duct, azygos vein, splanchnic nerves, and vagus nerves.

The heart is quite analogous to the lung, as the pericardium has as its two inner layers the visceral and parietal serous layers. However there is now a third layer, the fibrous pericardium, which essentially has the parietal layer as its inner lining.

The heart is attached at its bottom surface to the diaphragm, so it moves up and down with inspiration and expiration.

The lung apex extends over the clavicle and first rib. The parietal pleura pretty much extends over the entire rib cage laterally and posteriorly, tapering up the xiphoid process anteriorly. The left lung is more circumscribed along its medial edge anteriorly due to the heart pressing into it. The lung extends past the xiphoid process in the front and down past the T10 vertebra in the front.

The left lung has two lobes; the right, three. The left lung has the cardiac, diaphragm, and aortic impressions. The right lung has the cardiac, diaphragm, esophageal, and tracheal impressions. The right main bronchus is steeper, wider, and shorter than the left; it is more likely to trap and lodge foreign objects. It branches into the right superior lobar bronchus and intermediate bronchus before entering the hilum, where the intermediate branches into the right middle lobar bronchus and right lower lobar bronchus. The left main bronchus branches into the left superior lobar bronchus and left inferior lobar bronchus. The lobar bronchi on both sides then branch into tertiary (segmental) bronchi. The ridge between the right main bronchus and left main bronchus is called the carina; it is distorted and immobile if the tracheobronchial lymph nodes are enlarged (i.e. bronchogenic carcinoma).