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Skin is the body’s largest organ. It consists of two layers. The outermost layer is the epidermis, which is a stratified squamous epithelium. The second layer is the dermis, comprised of both loose and dense irregular connective tissue. Skin is classified as thick or thin depending on the thickness of the epidermis. Thick skin is found on the palms of the hands and the soles of the feet, whereas skin over the rest of the body is classified as thin. The epidermis is a layered structure with continuous turnover of cells called keratinocytes. Keratinocytes form from stem cells in the basal layer of the epidermis, and then migrate to the surface. As they migrate, they accumulate keratin and eventually undergo apoptosis forming the outermost layer of the epidermis, which sheds the apoptotic cells on a daily basis. In addition to keratinocytes, the epidermis contains melanocytes. These cells produce melanin, which the melanocytes transfer to keratinocytes. Melanin determines the color of skin and provides protection from UV radiation. Skin also contains hair follicles, eccrine sweat glands, apocrine sweat glands, and sebaceous glands, all of which are derived from the epidermis. Skin is richly innervated with free nerve endings and several different types of encapsulated sensory receptors. Common benign neoplasms of the skin are melanocytic nevi (moles), and acrochordons (skin tags).

Most medical schools test their students throughout the curriculum using in-house examinations written by the faculty who teach the courses. The authors assessed the quality of in-house examinations used in three U.S. medical schools.In 1998, nine basic science examinations from the three schools were gathered and each question was subjected to quality assessment by three expert biomedical test developers, each of whom has had extensive experience in reviewing and evaluating questions for the United States Medical Licensing Examination (USMLE) Steps 1 and 2. Questions were rated on a five-point scale: 1 = tested recall only and was technically flawed to 5 = used a clinical or laboratory vignette, required reasoning to answer, and was free of technical flaws. Each rater made independent assessments, and the mean score for each question was calculated. Mean quality scores for National Board of Medical Examiners (NBME) who were trained question writers were compared with the mean scores for question writers without NBME training. The raters' quality assessments were made without knowledge of the test writers' training background or the study's hypothesis.A total of 555 questions were analyzed. The mean score for all questions was 2.39 +/- 1.21. The 92 questions written by NBME-trained question writers had a mean score of 4.24 +/- 0.85, and the 463 questions written by faculty without formal NBME training had a mean score of 2.03 +/- 0.90 (p.01).The in-house examinations were of relatively low quality. The quality of examination questions can be significantly improved by providing question writers with formal training.

The authors describe their vision of what continuing medical education (CME) should become in the changing health care environment. They first discuss six types of literature (e.g., concerning learning and adult development principles, problem-based/practice-based learning, and other topics) that contribute to ways of thinking about and understanding CME. They then state their view that the Association of American Medical Colleges (AAMC) has made a commitment to helping CME be more effective in the professional development of physicians. In presenting their new vision of CME, the authors describe their interpretation of the nature and values of CME (e.g., optimal CME is highly self-directed; the selection and design of the most relevant CME is based on data from each physician's responsibilities and performance; etc.). They then present seven action steps, suggestions to begin them, and the institutions and organizations they believe should carry them out, and recommend that the AAMC play a major role in supporting activities to carry out these steps. (For example, one action step is the generation and application of new knowledge about how and why physicians learn, select best practices, and change their behaviors). Six core competencies for CME educators are defined. The authors conclude by stating that collaboration among the appropriate academic groups, professional associations, and health care institutions, with leadership from the AAMC, is essential to create the best learning systems for the professional development of physicians.

This article reviews the role of the kidneys in the regulation of acid-base balance. It is intended as a guide for those who teach this aspect of renal physiology to health professions students. An approach is described, which begins with an overview of acid-base balance and then proceeds to describe the details of renal H1 transport and the important role the production and excretion of NH 4 plays in the ability of the kidneys to generate new HCO 3 . In the overview, the role of the kidneys in acid-base balance is placed in context for the student by examining the impact of diet and cellular metabolism on acid-base balance. Also, the interactions between the kidneys and lungs to maintain extracellular HCO 3 concentration within a narrow range are described. This is followed by a detailed look at the cellular mechanisms of H1 secretion along the nephron, how these mechanisms are regulated, and how they result in the reabsorption of the filtered load of HCO 3 . Finally, the important role of NH 4 production and excretion in the generation of new HCO 3 is reviewed and highlighted.

Since the topic of the role of the kidneys in the regulation of acid-base balance was last reviewed from a teaching perspective (Koeppen BM. Renal regulation of acid-base balance. Adv Physiol Educ 20: 132–141, 1998), our understanding of the specific membrane transporters involved in H+, HCO3−, and NH4+ transport, and especially how these transporters are regulated in response to systemic acid-base disorders, has advanced considerably. In this review, these new aspects of renal function are presented, as are the broader and more general concepts related to the role of the kidneys in maintaining the acid-base balance. It is intended that this review will assist those who teach this aspect of human physiology to first-year health profession students.

With the development and refinement of the techniques of in vivo mi­ cropuncture and in vitro microperfusion of individual renal tubules, it has been possible to define the transepithelial electrophysiological properties of all regions of the mamm alian nephron (for reviews see 6, 9-11, 29, 66, 103, 104). Although these techniques have provided valuable insight into the mechanisms of ion transport, they are limited in that the cellular compart­ ment is treated as a "black box." In order to understand more precisely the cellular mechanisms of ion transport, it is necessary to obtain measurements of the driving forces and membrane conductances for ion movement across both the luminal and peritubular membranes of the cell. In this regard intracellular potentials and ion activities have been measured with routine success in several nonmammalian tissues, owing in part to the fact that the individual tubule cells are large and relatively easy to impale with micro­ electrodes (see the chapter by Boron & Sackin in this section). In addition, it has been possible to obtain intracellular recordings in several mammalian nephron segments (see Table 1). In this chapter we review the electrophysiology of the mammalian neph­ ron, with emphasis on information obtained with intracellular voltage

Morphological heterogeneity of the rabbit collecting duct. The localization of carbonic anhydrase by histochemistry, of Na-K-ATPase by immunocytochemistry and of rod-shaped intramembranous particles by freeze-fracture electron microscopy, was determined in the collecting duct of rabbits. In the cortical collecting duct (CCD), rod-shaped particles, which are abundant in intercalated cells were observed in both the apical and basolateral membrane of all intercalated cells examined. In the outer stripe of the outer medullary collecting duct (OMCDo) a high density of rod-shaped particles was found only in the apical membrane of intercalated cells. All cells of the inner stripe of the outer medullary collecting duct (OMCDi) had rod-shaped particles in the apical membrane but not in the basolateral membrane. As the collecting duct entered the inner medulla the density of rod-shaped particles decreased until they were virtually absent in the terminal segment. Na-K-ATPase, localized to the basolateral membrane, was more abundant in principal cells than in intercalated cells in the CCD. In the OMCDo, staining was equal in principal and intercalated cells. All cells of the OMCDi and the inner medullary collecting duct (IMCD) stained for Na-K-ATPase. Carbonic anhydrase in the CCD was localized to the cell membranes and cytoplasm of intercalated cells. Principal cells did not stain for carbonic anhydrase. A similar pattern was seen in the OMCDo. In the outer region of the OMCDi most cells did not stain for carbonic anhydrase, whereas in the inner region the apical and lateral membranes of all cells stained for carbonic anhydrase. Weak cytoplasmic staining was occasionally seen. A similar pattern was seen in the initial half of the IMCD, while the terminal half of the IMCD did not stain. In this study, the localization of enzymes and rod-shaped intramembranous particles associated with Na + , K + , and H + transport shows both segmental and cellular heterogeneity, and correlates with the known transport properties of tubule segments. The distribution of these enzymes and rod-shaped intramembranous particles is different in rabbits and rats, and may explain some of the functional differences between homologous segments in these species.

Intracellular microelectrode techniques were used together with inhibitors of Na+ transport (amiloride) and H+ transport (acetazolamide and SITS) to identify principal cells and intercalated cells in the outer stripe of the rabbit outer medullary collecting duct. The principal cell (n = 9) had a basolateral membrane voltage (Vbl) of -64.7 +/- 3.2 mV, a fractional resistance of the apical membrane (fRa = Ra/Ra + Rbl) of 0.82 +/- 0.02, and a K+-selective basolateral membrane. Luminal amiloride hyperpolarized Vbl by 10.3 +/- 2.1 mV and increased fRa to near unity (n = 7). Bath acetazolamide and SITS were without effect on these parameters. The intercalated cell (n = 5) had a Vbl of -25.0 +/- 3.2 mV, a fRa of 0.99 +/- 0.01, and a Cl(-)-selective basolateral membrane. Bath acetazolamide or SITS hyperpolarized Vbl by 26.4 +/- 8.2 mV. Luminal amiloride did not alter Vbl of this cell. The differential effects of the inhibitors also indicate that the principal and intercalated cells are probably not directly coupled electrically.

Patch clamp techniques were used in study of the apical membrane of isolated renal cortical collecting ducts. Whereas on-the-cell patches (reported previously) gave channel activity due primarily to K+, isolated inside-out patches of the same membranes bathed with 150 mM Na+, 5 mM K+, and 1 mM Ca2+ gave channel activity due primarily to Na+. Na+ channels could remain either open or closed for periods of milliseconds to minutes. Although unitary currents of tenths of a pA were observed routinely, patch activity could change spontaneously between quiescent and violent with ‘apparent’ unitary currents of several pA. It was not possible to rule out the idea that the complex activity of the patches was due to synchronous or near synchronous openings/closings of several channels of identical unitary current. The unpredictable spontaneous changes of patch activity make difficult the design of experiments to test for the influence of agents expected or suspected to alter channel behavior.

This article has examined the process of urinary acidification from the perspective of events occurring at the cellular and single nephron level. Accordingly, the reabsorption of filtered HCO3- and the titration of urine buffers can be ascribed to the fundamental process of H+ secretion. The precise mechanism of H+ secretion by the tubule cells, the rate by which this occurs, and the factors regulating transport differ between nephron segments. Despite these differences, the cellular process of urinary acidification can be viewed as the extrusion of H+ against an electrochemical gradient across the luminal cell membrane and the movement of an HCO3- equivalent across the basolateral cell membrane. In the proximal tubule (convoluted and straight portions) approximately 90 per cent of the filtered load of HCO3- is reabsorbed. This occurs without the development of large lumen-to-blood pH gradients. The secretion of H+ across the luminal membrane occurs primarily via an electrically neutral Na-H exchange mechanism. Since it is the lumen-to-cell Na+ gradient which provides the energy, the secretion of H+ is a "secondary active" process dependent on the function of the Na-K-ATPase located in the basolateral cell membrane. During the elaboration of an acid urine, the distal nephron (distal convoluted tubule and collecting duct) reabsorbs that portion of the filtered HCO3- escaping proximal reabsorption, titrates luminal buffers, and lowers urine pH. The secretion of H+ occurs by a "primary active" mechanism, which involves the extrusion of H+ across the luminal cell membrane by an electrogenic H+ pump driven by the hydrolysis of ATP. The rate at which H+ is secreted depends on the electrochemical gradient for H+ across the luminal membrane. Thus, changes in both lumen pH and potential will effect H+ secretion, with low lumen pH inhibiting transport and large lumen-negative potentials stimulating transport. In some animals, depending on their homeostatic needs, secretion of HCO3- by the distal nephron can also occur. This process is localized to the distal convoluted tubule and the cortical collecting duct and appears to represent a transport system distinct from that responsible for H+ secretion.

Electrophysiological studies were carried out on single perfused cortical and medullary collecting ducts to define the potassium and sodium transport properties of their apical and basolateral cell membranes. In addition, the effects of chronic mineralocorticoid hormone treatment on the mechanism of transport of potassium ions were evaluated. Studies included the measurement of transepithelial and cell potentials, and the resistance of individual cell membranes. The apical cell membrane of principal cells of the cortical collecting duct is characterized by separate potassium and sodium conductances. The basolateral cell membrane has also a potassium conductance, whereas the intercellular shunt pathway is largely permeable to chloride ions. Stimulation of potassium secretion by mineralocorticoids is associated with the following events. Increased cell potassium uptake across the basolateral cell membrane due to stimulation of Na-K ATPase and a more favorable electrical driving force for passive entry, facilitated exit of potassium from the cell to the tubule lumen by a more favorable electrochemical gradient (apical cell membrane depolarization) and enhanced potassium secretion by in increase of the potassium conductance of the apical cell membrane. Some properties of single potassium channels in the apical membrane of rabbit cortical collecting tubules are also described.