книги студ / color atlas of physiology 5th ed[1]. (a. despopoulos et al, thieme 2003)

Reabsorption and Excretion of

Phosphate, Ca2+ and Mg2+

Henle and is paracellular, i.e., passive (!A4a and p. 163 B5, B7). The lumen-positive transepithelial potential (LPTP) provides most of the driving force for this activity. Since Ca2+ reabsorption in TAL depends on NaCl reabsorption, loop diuretics (!p. 172) inhibit Ca2+ reabsorption there. PTH promotes Ca2+ reabsorption in TAL as well as in the distal convoluted tubule, where Ca2+ is reabsorbed by transcellular active transport (!A4b). Thereby, Ca2+ influx into the cell is passive and occurs via luminal Ca2+ channels, and Ca2+ efflux is active and occurs via Ca2+-ATPase (primary active Ca2+ transport) and via the 3Na+/1Ca2+ antiporter (secondary active Ca2+ transport). Acidosis inhibits Ca2+ reabsorption via unclear mechanisms.

Urinary calculi usually consist of calcium phosphate or calcium oxalate. When Ca2+, Pi or oxalate levels are increased, the solubility product will be exceeded but calcium complex formers (e.g., citrate) and inhibitors of crystallization (e.g., nephrocalcin) normally permit a certain degree of supersaturation. Stone formation can occur if there is a deficit of these substances or if extremely high urinary concentrations of Ca2+, Pi and oxalate are present (applies to all three in pronounced antidiuresis).

Magnesium metabolism and reabsorption.

Since part of the magnesium in plasma (0.7–1.2 mmol/L) is protein-bound, the Mg2+ conc. in the filtrate is only 80% of the plasma magnesium conc. Fractional excretion of Mg2+, FEMg, is 3–8% (!A1,2). Unlike Ca2+, however, only about 15% of the filtered Mg2+ ions leave the proximal tubule. About 70% of the Mg2+ is subject to paracellular reabsorption in the TAL (!A4 and p. 163 B5, B7). Another 10% of the Mg2+ is subject to transcellular reabsorption in the distal tubule (!A4b), probably like Ca2+ (see above).

Mg2+ excretion is stimulated by hypermagnesemia, hypercalcemia, hypervolemia and loop diuretics, and is inhibited by Mg2+ deficit, Ca2+ deficit, volume deficit, PTH and other hormones that mainly act in the TAL.

The kidney has sensors for divalent cations like Ca2+ and Mg2+ (!p. 36). When activated, the sensors inhibit NaCl reabsorption in the TAL which, like loop diuretics, reduces the driving force for paracellular cation resorption, thereby diminishing the normally pronounced Mg2+ reabsorption there.

Final urine

5–20%

3–8% 0.5–3%

Plate 7.16 Reabsorption and Excretion of Phosphate

179

dosterone administration or secretion. The maximum effects are observed after several hours. Aldosterone increases Na+ reabsorption, thereby depolarizing the luminal cell membrane (!B3). Consequently, it increases the driving force for K+ secretion and increases K+ conductance by increasing the pH of the cell. Both effects lead to increased K+ secretion. Aldosterone also has a very rapid (few seconds to minutes) non-genomic effect on the cell membrane, the physiological significance of which has yet to be explained.

The capacity of the K+ excretory mechanism increases in response to long-term increases in the K+ supply (K+ adaptation). Even when renal function is impaired, this largely maintains the K+ balance in the remaining, intact parts of the tubular apparatus. The colon can then take over more than 1/3 of the K+ excretion.

Mineralocortico(stero)ids. Aldosterone is the main mineralocorticoid hormone synthesized and secreted by the zona glomerulosa of the adrenal cortex (!D and p. 294ff.). As with other steroid hormones, aldosterone is not stored, but is synthesized as needed. The principal function of aldosterone is to regulate Na+ and K+ transport in the kidney, gut, and other organs (!D). Aldosterone secretion increases in response to (a) drops in blood volume and blood pressure (mediated by angiotensin II; !p. 184) and (b) hyperkalemia (!D). Aldosterone synthesis is inhibited by atriopeptin (!p. 171 A4).

Normal cortisol concentrations are not effective at the aldosterone receptor only because cortisol is converted to cortisone by an 11!-hydroxysteroid oxidoreductase in aldosterone’s target cells.

Hyperaldosteronism can be either primary (al- dosterone-secreting tumors of adrenal cortex, as observed in Conn’s syndrome) or secondary (in volume depletion, !p. 184). Na+ retention resulting in high ECF volumes and hypertension as well as a simultaneous K+ losses and hypokalemic alkalosis are the consequences. When more than about 90% of the adrenal cortex is destroyed, e.g. by autoimmune adrenalitis, metastatic cancer or tuberculosis, primary chronic adrenocortical insufficiency develops (Addison’s disease). The aldosterone deficit leads to a sharp increase in Na+ excretion, resulting in hypovolemia, hypotension and K+ retention (hyperkalemia). As glucocorticoid deficiency also develops, complications can be life-threatening, especially under severe stress (infections, trauma). If only one gland is destroyed, ACTH causes hypertrophy of the other (!p. 297 A).

7 Kidneys, Salt, and Water Balance

184

Overview

Blood is pumped from the left ventricle of the heart to capillaries in the periphery via the arterial vessels of the systemic (or greater) circulation and returns via the veins to the right heart. It is then expelled from the right ventricle to the lungs via the pulmonary (or lesser) circulation and returns to the left heart (!A).

The total Blood volume is roughly 4–5 L (!7% of the fat-free body mass; !table on p. 88). Around 80% of the blood circulates through the veins, right heart and pulmonary vessels, which are jointly referred to as the low pressure system (!A, left). These highly distensible capacitance vessels function as a blood reservoir in which blood is stored and released as needed via venous vasoconstriction (!e.g., p. 218). When the blood volume increases— due, for example, to a blood transfusion—over 99% of the transfused volume remains in the low-pressure system (high capacitance), while only !1% circulates in the arterial high-pres- sure system (low capacitance). Conversely, a decrease will be reflected almost entirely by a decrease in the blood stores in the lowpressure system. Central venous pressure

(measured in or near to the right atrium; normally 4–12 cm H2O) is therefore a good indicator of blood volume (and ECF volume) in individuals with a normally functioning heart and lungs.

Cardiac output (CO). The cardiac output is calculated as heart rate (HR) times stroke volume (SV). Under normal resting conditions, the CO is approx. 70 [min–1] " 0.08 [L] = 5.6 L/ min or, more precisely, a mean 3.4 L/min per m2 body surface area. An increase in HR (up to about 180 min–1) and/or SV can increase the CO to 15–20 L/min.

The distribution of blood to the organs arranged .in parallel in the systemic circulation

(!A, Q values) is determined by their functional priority (vital organs) and by the current needs of the body (see also p. 213 A). Maintaining adequate cerebral perfusion (approx. 13% of the resting CO) is the top priority,

186not only because the brain is a major vital organ, but also because it is very susceptible to

hypoxic damage (!p. 130). Myocardial perfusion via coronary arteries (approx. 4% of the CO at rest) must also be maintained, because any disruption of cardiac pumping function will endanger the entire circulation. About 20 to 25% of the CO is distributed to the kidneys. This fraction is very large relative to the kidney weight (only 0.5% of body mass). Renal blood flow is primarily used to maintain renal excretory and control functions. Thus, renal blood flow may be reduced transiently in favor of cardiac and cerebral perfusion, e.g., to ward off impending shock (!p. 218). During strenuous physical exercise, the CO increases and is alloted mainly to the skeletal muscle. During digestion, the gastrointestinal tract also receives a relatively high fraction of the CO. Naturally, both of these organ groups cannot receive the maximum blood supply at the same time (!p. 75 A). Blood flow to the skin (approx. 10% of the resting CO) mainly serves the purpose of heat disposal (!p. 222ff.). The cutaneous blood flow rises in response to increased heat production (physical work) and/ or high external temperatures and decreases (pallor) in favor of vital organs in certain situations (e.g., shock; !p. 218).

The total CO flows through the pulmonary circulation as it and the systemic circulation are arranged in series (!A). Oxygen-depleted (venous) blood is carried via the pulmonary arteries to the lungs, where it is oxygenated or “arterialized.” A relatively small quantity of additional oxygenated blood from the systemic circulation reaches the lung tissue via the bronchial arteries. All blood in the pulmonary circulation drains via the pulmonary veins.

Peripheral resistance. Flow resistance in the pulmonary circulation is only about 10% of the total peripheral resistance (TPR) in the systemic circulation. Consequently, the mean pressure in the right ventricle (approx. 15 mmHg = 2 kPa) is considerably lower than in the left ventricle (100 mmHg = 13.3 kPa). Since the resistance in the lesser arteries and arterioles amounts to nearly 50% of TPR (!A, top right), they are called resistance vessels.

Plate 8.1 Overview

187