Table of contents :

• water metabolism
• daily intake : 2,300 mL/day
• dietary water : 2,100 mL/day
• facultative intake : 1000 mL/day
• food : 800 mL/day
• drinks : 500 mL/day
• metabolic water from endogenous oxidations
• carbohydrate oxidation : 200 mL/day
• lipid and protein oxidation : 100 mL/day
• daily losses
• perspiratio insensibilis / insensible water loss (IWL) : 500-700 mL/day (+ 150-200 mL/day for every °C above 37°C)
• cutaneous diffusion : 350 mL/day
• URT evaporation : 350-400 mL/day (under hyperventilation : 650 mL/day; increased in cold environments, where P_{H2O, air} ~ 0)
• sweat : 100 mL/day (under severe exercise : 5,000 mL/day)
• gastrointestinal losses :

source	volume (mL)	Na+ (mEq/L)	Cl- (mEq/L)	K+ (mEq/L)	HCO3- (mEq/L)	H+ (mEq/L)
stomach	1000-4200	20-120	130	10-15	-	300
duodenum	100-2000	110	115	15	10
ileum	1000-3000	80-150	60-100	10	30-50
colon (diarrheal)	500-1700	120	90	25	45
bile	500-1700	140	100	5	25
pancreas	500-1700	140	30	5	115

98% of secretions are reabsorbed by :
• jejunum (4 L / die)
• ileum (4 L / die)
• colon (0.8 L / die)
=> 100-200 mL/day in stools (higher in vomiting, diarrhea, enterostomy)
• urine : 1,400 mL/day (under intense exercise : forced urinary volume = 500 mL/day; up to 20 L/day in severe polydipsia)





• water distribution : 58-60% of the body mass in males and 50-55% in females (i.e. total body water (TBW) = 42 L in an healthy adult with body mass = 70 kg). It can be estimated with :
• % of weight :
• for females : 55%
• for males : 60%
• Watson formula :
• for females : - 2,097 + 0,2466 x weight(kg) + 0,1069 x height(cm)
• for males = + 2,447 + 0,3362 x weight(kg) + 0,1074 x height(cm) - 0,09156 x age(years)
• Hume formula :
• for females = - 35,270121 + 0,183809 x weight(kg) + 0,34454 x height(cm)
• for males = - 14,012934 + 0,296785 x weight(kg) + 0,194786 x height(cm)
• 55-75% (28 L) in intracellular fluid (ICF) (35% in breast-fed, 30% at age 10, 40% in adults)
• cations :
• Na⁺ : 12.0 mEq/L
• Ca²⁺ : 4.0 mEq/L
• K⁺ : 150 mEq/L
• Mg²⁺ : 34.0 mEq/L
• anions
• Cl^- : 4.0 mEq/L
• HCO₃^- : 12.0 mEq/L
• HPO₄^2-, H₂PO₄^- : 40 mEq/L
• proteins : 54 mEq/L
• other : 90 mEq/L
• 24-45% (14 L) in extracellular fluid (ECF) (40% in breast-fed, 30% at age 10, 16% in adults)
• cations :
• Na⁺ : 142.0 mEq/L
• Ca²⁺ : 2.5 mEq/L
• K⁺ : 4.3 mEq/L
• Mg²⁺ : 1.1 mEq/L
• anions
• Cl^- : 104.0 mEq/L
• HCO₃^- : 24.0 mEq/L
• HPO₄^2-, H₂PO₄^- : 2 mEq/L
• proteins : 14 mEq/L
• other : 5.9 mEq/L
• 75% (ie. 30% of TBW = 10.5-11 L) in interstitium between cells
• 25% (ie 10% of TBW = 3-3.5 L) in plasma and lymph within vessels
Water crosses cellular membranes to maintain osmotic equilibrium.
• osmolarity : the concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution
• tonicity : the state of tissue tone or tension; in body fluid physiology, the effective osmotic pressure equivalent
• plasma osmotic activity, effective osmolarity or tonicity
• osmolality : the concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the colligative properties of solutions: osmotic pressure, boiling point elevation, freezing point depression, and vapor pressure lowering
As solute concentration in biological fluids is usually very low, in clinical practice osmolarity is used instead of osmolarity.
Osmolytes are actively synthetised or secreted to preserve cells from swelling or shrinking (osmotic adaptation) in chronic electrolyte unbalances :
• effective osmolytes :
• inorganic : ₁₁Na⁺, ₁₉K⁺,
• organic : glucose, inositol, betaine, glutamine
• uneffective osmolytes : urea
• thirst is sensed when plasma osmolality > 295 mosmol / kg
• paranephrium : connective tissue around and near the kidney, beyond the renal fascia
• perinephrium : peritoneal envelope and other tissues around the kidney within the renal fascia
• perinephric or perirenal fat / capsula adiposa renis / adipose capsule of kidney / fatty capsule of kidney : the investment of fat surrounding the fibrous capsule of the kidney and continuous at the hilum with the fat in the renal sinus
• Gerota's capsule or fascia / renal fascia / fascia renalis : a thin membranous sheath that encloses the kidney, formed by condensation of the retroperitoneal connective tissue surrounding the kidney and the perirenal fat
• Toldt's membrane : the part of the renal fascia anterior to the kidney.
• Zuckerkandle's fascia : the part of the renal fascia posterior to the kidney.
• ontogenesis :
• ductus mesonephricus / mesonephric duct / ductus Wolffi / wolffian duct / duct of Wolff / Leydig's duct / canal of Oken
• pronephros / pronephron : the 2.5 mm-sized primordial kidney consisting of 6-10 pairs of tubules; a vestigial excretory structure or its rudiments developing in the embryo at 4 weeks, before the mesonephros. Although nonfunctional, its duct is later used by the mesonephros, which arises caudal to it.
• pronephric tubules : the tubules constituting the primordial kidney of vertebrates; they are rudimentary in amniotes.
• mesonephros / corpus Wolffi / mesonephron / middle kidney / wolffian body : the temporary kidney of amniotes, excretory organ of the embryo (week 4), arising caudal to the pronephros or pronephric rudiments and using its duct; it consists of a long tube in the lower part of the body cavity, running parallel with the vertebral axis and joined at right angles by a row of twisting tubes
• nephrogenic cord : a longitudinal cordlike part of the urogenital ridge, formed of fused or never separated nephrotome plates, that gives rise to the segmental or mesonephric tubules and part of the metanephric tubules.
• nephric blastema : the extension of nephrogenic cord tissue, caudal to the mesonephros, into which the ureteric buds grow to initiate development of the definitive mammalian kidney.
• paradidymis / organ of Giraldés / parepididymis / massa innominata
• metanephros / definite, definitive, or hind kidney : the primordium of the permanent kidney, which develops later (week 5) than and caudal to the mesonephros, from the nephrogenic cord (from Bowman's capsules to distal convoluted tubules) and mesonephric duct (from collecting tubules to ?)
• metanephric blastema : the concentrated mass of mesodermal cells about the metanephric bud in a young embryo; the cells of the cap form the uriniferous tubules of the permanent kidney.
• metanephric tubules : the tubules comprising the permanent kidney of amniotes.
• the common nephric duct does not differentiate into the trigone but instead undergoes apoptosis, a crucial step for ureter transposition controlled by vitamin A-induced signals from the primitive bladder. Ureter abnormalities occur in 1-2% of the human population and can cause obstruction and end-stage renal disease^ref
• phylogenesis : in all of the vertebrates, beginning from the most primitive ones, an universal principle of structural, functional and chemical organization of the nephron is noted. The main trend of progressive evolution of kidney function (both in phylogenesis of vertebrates and ontogenesis of birds and mammals) is the increase of the intensity of filtration-reabsorption mechanism of urine formation. The development of secretory apparatus is considered as an adaptation to the conditions in which this mechanism is not sufficient to provide the necessary level of excretion. It is suggested that secretory mechanism is formed in close relation to cellular system of reabsorption of sodium and chloride. The first step in the evolution of osmoregulation in vertebrates involved development of water-impermeable epithelium which depended on specific distribution of aquaporins in plasma membranes, secretion of autacoids, formation of water-impermeable cell contacts with a high electrical resistance. Migration of vertebrates to the land was associated with appearance of the ability to regulate osmotic permeability of epithelium in a number of organs involving vasotocin and other pituitary hormones, insertion of aquaporins into the luminal plasma membrane. Enhancement of the renal role in the water-salt balance, intensification of the kidney function was due to a rise in renal circulation, glomerular filtration rate, and tubular reabsorption which, despite the increase in the energy expenditure, provided for an obvious enhancement of the renal work efficiency in maintaining the constancy of the internal medium. Colonisation of desert regions became possible in birds and mammals due to development of the system of urine osmotic concentration. Unlike the accepted point of view that this depended on the appearance of Henle's loops, the statement is substantiated that the leading role in this process is played by differentiation of the kidney into the cortex and medulla, as nephron loops similar to Henle's loop have been revealed in the lamprey. In the vertebrates, the evolution shifted from the polyorgan to mono-organ type of osmotic homeostasis maintenance, with the leading role of the kidney in maintaining physico-chemical constants of the internal medium fluids^ref. The presence in lamprey kidney of a loop which is similar to Henle's loop in mammals and birds indicates that the development of the system of osmotic concentration conditioned by the formation in the kidney of the medulla and from a sharp increase in renal arterial blood supply^ref. While neonatal kidneys are not powerful in concentrating urine, they already dilute urine as efficiently as adult kidneys. The renal medullary tubule organization of neonatal rats shares a tremendous similarity with avian renal medulla : the qualitative changes in the organization of medullary tubules may be primarily responsible for the immature urine-concentrating ability in mammalian neonates^ref.
• kidney / ren (nephrology) : either of the 2 organs in the lumbar region that filter the blood, excreting the end-products of body metabolism in the form of urine, and regulating the concentrations of hydrogen, sodium, potassium, phosphate, and other ions in the extracellular fluid. The kidney is of characteristic shape, and presents a notch on the inner, concave, border, known as the hilus, which communicates with the cavity or sinus of the kidney and through which the vessels, nerves, and ureter pass.
• Sizes :
• vertical diameter : 11 cm (reduced to 7 cm in some nephropathies)
• horizontal diameter : 5-7.5 cm
• transverse diameter : 2.5 cm
• Vascularization : each kidney receives 10% of cardiac output via renal artery

vessel	pressure [mmHg] at...		% of renal vascular resistance
	beginning	end
renal artery	100	100	0
interlobar, arcuate, and intralobular artery	100	85	16
afferent arteriole	85	60	26
glomerular capillaries	60	59	1
efferent arteriole	59	18	43
peritubular capillaries	18	8	10
interlobar, interlobular, and arcuated vein	8	4	4
renal vein	4	4	0

• afferent arteriole has fenestrated endothelium (80-90 nm) with polyanionic protein which mediates albumin repulsion
• Isaacs-Ludwig arteriole : an arteriolar twig that sometimes branches from the afferent glomerular arteriole of the kidney to communicate directly with the tubular capillary plexus
• renal glomeruli / glomeruli renis / glomeruli of kidney / malpighian glomeruli / Ruysch's glomeruli : globular tufts of capillaries (Ø = 200 mm), one projecting into the expanded end or capsule of each of the uriniferous tubules, which together with its surrounding capsule (glomerular capsule) constitute the renal corpuscle. It has a filtration surface = 0.130 mm²
• glomerular basement membrane (GBM) (2,400-3,500 Å) consists of :
• lamina rara externa
• lamina densa
• lamina rara interna
It is a filter for molecules with M_r > 40-50 kDa. GAGs within the GBM prevent protein crystallization.
• efferent arteriole continues into peritubular capillary plexus / vasa recta of juxtamedullary nephrons and collecting ducts and then into renal vein
• Anatomy
• Brödel's white line : a longitudinal white line on the anterior surface of the kidney near the convex border.
• renal cortex / cortex renalis / cortex renis / cortical substance of kidney : the outer part of the substance of the kidney, composed mainly of glomeruli and convoluted tubules (both proximal and distal). 8-12 mm thickness
• cortical arches
• columnae renales [Bertini] / columnae bertini / renal columns of Bertin / cortical septae : inward extensions of the cortical structure of the kidney, between the renal pyramids
• renal medulla is arranged into 10 to 15 pyramides renales [Malpighii] / renal pyramids (conical (not pyramidal !) masses that make up the medullary substance of the kidney, whose bases are in the cortex and whose blunted apices, which are called papilla renalis / renal papilla, project into the renal sinus; they contain the loops of Henle, the collecting ducts, and the arteriolae rectae renis)
• outer zone of renal medulla : the part of the medulla nearest to the cortex; containing the medullary part of the distal straight tubule as well as the outer part of the medullary collecting duct. It is subdivided into
• outer stripe : in the outer zone of the renal medulla, the part next to the cortex; it contains thick descending and thick ascending limbs of the loop of Henle.
• inner stripe : in the outer zone of the renal medulla, the part next to the inner zone and away from the cortex; it contains thin descending and thick ascending limbs of the loop of Henle
• inner zone of renal medulla : the part of the medulla farthest in from the cortex, containing ascending and descending limbs of the thin tubule as well as the inner part of the medullary collecting duct.
• renal sinus / sinus renalis : a cavity within the substance of the kidney, occupied by ...
• vessels
• nerves
• fat
• pelvis renalis / renal pelvis : the expansion from the upper end of the ureter into which the calices of the kidney open; ordinarily lodged within the renal sinus, under certain conditions, as in a long kidney or obstruction of the ureteropelvic junction, a large part of it may be outside the kidney (extrarenal pelvis)
• calices renales / renal calices / calyces renales / infundibula of kidney : the recesses of the pelvis of the kidney which enclose the pyramids
• calices renales majores / renal calices / calyces renales majores / greater renal calices. : the 2 or more larger subdivisions of the renal pelvis, into which the minor calices open
• calices renales minores / minor renal calices / calyces renales minores : a varying number of smaller subdivisions of the renal pelvis which enclose the pyramids, and open into the major calices
• microcalix / microcalyx : a very small renal calix arising by caliceal branching, usually at the side of a calix of normal size
• nephron (urothelial cells) : the anatomical and functional unit of the kidney (250,000-1,200,000 per kidney; average = 1,600,000), consisting of ..


• corpuscula renis / renal corpuscles / malpighian corpuscles / acinus renalis [malpighii] / acinus renis [malpighii] / malpighian bodies of kidneys : bodies forming the beginnings of the nephrons, each consisting of a tuft of capillaries (the glomerulus), surrounded by an expanded portion of the renal tubule (the glomerular capsule)
• urinary pole
• vascular pole
• renal glomeruli
• intraglomerular mesangial cells secrete mesangial matrix
• Bowman capsule
• capsular epithelium consists of renal glomerular parietal cell
• capsular (Bowman's) space
• glomerular epithelium consists of renal glomerular visceral cell / podocyte (length : 3,000-5,000 Å) : a modified epithelial cell of the capsular epithelium of the renal glomerulus, having a small perikaryon and a number of primary processes / trabeculae and secondary footlike radiating processes (pedicels / foot processes) separated by filtration slits / slit pores (width from 20-300 Å to 800-1,000 Å; membrane thickness = 50-70 Å; containing slit diaphragms) of 25-50 nm and embrace the basal lamina of glomerular capillaries

Histological stainings :
• PAS marks mesangium and GBM in purple
• H&E marks mesangium and epithelium
• Ag salts marks GBM and mesangial matrix
• renal tubules / tubuli renales / uriniferous tubule / uriniparous tubule
• proximal convoluted tubule / tubulus contortus proximalis
• thin tubule / tubulus attenuatus : part of the renal tubule where the walls are especially thin, extending from the proximal straight tubule to the distal straight tubule; this concept is now considered outdated
• proximal straight tubule / tubulus rectus proximalis
• Henle's tubule / ansa nephroni
• distal straight tubule / tubulus rectus distalis
• distal convoluted tubule / tubulus contortus distalis
• renal collecting tubule / tubulus renalis colligens
• principal cells : light-staining cells of the renal collecting tubules that transport water in response to ADH and sodium in response to aldosterone.
• intercalated cells : dark-colored cells in the renal collecting tubules that are responsible for acidification of the urine
• straight collecting tubule / tubulus colligens rectus : the lower straight part of the renal collecting tubule
• arcuate renal tubule / tubulus renalis arcuatus / connecting tubule / junctional tubule
• Bellini's tubule / ductus papillaris
• cortical collecting tubule : the more proximal parts of the renal tubule, which lie within the cortex.
• medullary collecting tubule : the distal part of the renal tubule, including the loop of Henle, lying within the medulla, which opens at the apex of a renal papilla.
• Ferrein's medullary rays : the portions of the renal tubules making up the pars radiata of the lobules of the renal cortex, formed by convergence of straight collecting tubules as they descend
Nephrons are located within the renal cortex and can be classified into
• subcapsular nephrons
• mediocortical nephrons
• iuxtamedullary nephrons (long-loop nephrons) reabsorb most H₂O.
• juxtaglomerular (JG) apparatus or complex : a complex that acts as a feedback mechanism in the autoregulation of the glomerular filtration rate, comprising :
• juxtaglomerular cells (JGC) / granular cells / myoepithelioid cells : specialized smooth muscle cells, located in the tunica media of the afferent glomerular arterioles and containing renin secretory granules. They are innervated by orthosympathetic fibers via b₁ AR.
• juxtaglomerular index : semiquantitative estimation of the degree of granulation of juxtaglomerular cells, obtained by a counting method and expressed as a ratio to the number of glomeruli.
• macula densa cells
• peripolar cells
• extraglomerular mesangial cell / lacis cells of the polkissen / Goormaghtigh cells : lacelike cells with pale-staining of the polkissen, having numerous processes and connecting gap junctions; thought to provide electrical coupling among themselves and to the mesangium and glomerular arterioles

• glomerular filtration rate (GFR) = K_f ^. (P_glomerulus - P_{Bowman's capsule} - p_glomerulus + p_{Bowman's capsule}) = 12.5 ^. (60 -18 - 32 + 0) = CL_inulin = 80-125 mL/min or mL/min/(1.73 ^. m²_BSA) = 120-180 L/die. It is ... :
• decreased by :
• noradrenaline
• adrenalin
• endothelin
• increased by :
• prostaglandins
• nitric oxide (NO)
• stabilized (prevention of decrease) by angiotensin II

	molecular mass (Mr)	filtrability = filtration ratex / filtration rateH2O	filtered load / tubular load (FLx) = GFR . [x]plasma . filtrability  [mg/min]	reabsorbed load (RLx)	% reabsorption of FL	secreted load (SLx) by proximal tubules	extraction fraction	excreted load (ELx) = (furine in 24 hrs . [x]urine) / (24h . 60')  [mg/min] = FLx - RLx + SLx	clearancex (Clx) = Vplasma cleared by x / t = ELx / [x]plasma [mL/min]
glucose	180	1.0	180 mEq/die	= FLx (threshold = 320 mg/min)	100	0		0	0
HCO3-	60	1.0	4,320 mEq/die	4,318 (80-90% in proximal tubule, 10-20% in distal tubule)	>99.9			2
11Na+	23	1.0	25,560 mEq/die	25,410 (66% in proximal convoluted tubule, 25-30% in thick ascending limb of Henle's loop via Na+ / K+ / 2Cl- cosymporter, 5% in distal convoluted tubule via Na+/Cl- cosymporter, cortical collecting duct via	99.4			150 (< 1% FL)	0.9
17Cl-	35.5	1.0	19,440 mEq/die	19,260	99.1			180	1.3
19K+	39	1.0	720-756 mEq/die	90% in proximal convoluted loop (passively) and thick ascending limb of Henle's loop via Na+ / K+ / 2Cl- cosymporter	88			92	12
20Ca2+		1.0	150-250 mmol/die = 6-10 g/die	60% in proximal tubule; 25% in Henle's loop and 15% in distal tubule				2.5-10 = 0.1-0.4
12Mg2+		1.0		90%				4%
phosphates		0.9	4-6 g/die	(threshold : 0.10 mM/min)				15% = 0.5-1.4 g/die	25
53I-									30
urea	60		46.8 mEq/die	23.4	50			23.4	40-65. Formula = (U [mg/24 hr] x V [ml]) / (P [mg/dl] x 14,4)
creatinine			1.8 mEq/die	0	0	> 0 (32% of ELx; threshold = 16 mg/min)		1.8 = FLx	80-150 (male 97-137 ml/min;  female: 88-128 ml/min). Formula = (U [g/24 hr] x V [ml]) / (P [mg/dl] x 14400)
NH4+								uric acid = 8-12% of FL  ...  =>  total =  40-60 mmol/die
uric acid				98-100% of FL in proximal tubule; 40% of SL in distal tubule (threshold : 15 mg/min)		50% of RL
lactic acid				(threshold : 75 mg/min)
sulfates				(threshold : 0.06 mM/min)
amino acids				(threshold : 1.4 mM/min)	100			0
inulin : an indigestible vegetable starch, (C6H10O5)4,  occurring in the rhizome of Compositae. It is a polymer of fructofuranose, yields fructose on hydrolysis	648	1.0		0	0	0		= FLx	125 in young males (in females value = 85-90% of males)
p-amino hippuric acid (PAH / PAHA) : glycine amide of p-amino benzoic acid						> 0 (threshold = 80 mg/min) (secreted by distal convoluted tubule)	90%		650 (below plasma threshold)
H2O	18	1.0
plasma proteins				(threshold : 30 mg/min)
myoglobin	17,000	0.75
albumin	69,000	0.005

• osmolar clearance (CL_osm) = (f_{urine in 24 hrs} ^. osm_urine) / (24h ^. 60' ^. osm_plasma) [mOsm/min]
• free water clearance (CL_H2O) = V - CL_osm
• extraction fraction_x = [x]_{renal artery} - [x]_{renal vein}
• renal blood flow (RBF) = DP / R_t = (CL_PAH / extraction fraction) ^. [1 / (1-Hct)] = ([PAH]_urine ^. f_urine^. [PAH]_{renal artery}) / ([PAH]_{renal artery} ^.([PAH]_{renal artery} - [PAH]_{renal vein]} ) ^. (1-Hct)) = ([PAH]_urine^.f_urine) / [([PAH]_{renal artery} - [PAH]_{renal vein]} ) ^. (1-Hct)+
• O₂ Fick method
• dye dilution method
As 10% of the renal plasma flow (RPF) = RBF ^. (1- Hct) just nourishes the renal parenchyma but is not filtered, a correction factor is needed to calculate the ...
• effective plasma renal flow (ERPF) = RBF ^. [(1- Hct) ^. 0.9] = CL_{PAH below threshold}
• filtration fraction (FF) = GFR / ERPF = CL_inulin / CL_{PAH below threshold} = 125 / 650 = 0.19
• tubular maximum (Tm) : the highest rate in milligrams per minute at which the renal tubules can transfer a substance either from the tubular luminal fluid to the interstitial fluid or from the interstitial fluid to the tubular luminal fluid
• kinetics of transtubular processes :
• transports limited by the number of transporters : saturable (with a threshold), high affinity, generated high gradients (e.g. K⁺, Glc, amino acids)
• transports limited by gradient (paracellular leakage in proximal tubule) and ultrafiltrate flow rate (the higher the rate, the lesser the driving force for the leakage, the higher the driving force for diffusion). It is not saturable under physiological concentrations, but has low affinity (e.g. Na⁺, H⁺, ..)
• in proximal convoluted tubule : obliged reabsorption of 65% of GFR (all glucose via SGLT-2 and GLUT-2; protein micropinocytosis)
• in Henle's loop : it causes the renal medulla to become hyperosmotic
• in distal convoluted tubule and collecting duct : regulable reabsorptions (facultative reabsorption of H₂O and Na⁺)
• Na⁺Cl^- and H₂O reabsorption : ATPase creates  gradient => Na⁺ is reabsorbed according to electrical gradient => H₂O is reabsorbed osmotically => concentration of urea and Cl^- => Cl^- and urea reabsorption by electrochemical gradient (V = -7 mV in lumen and 0 in plasma) => further H₂O reabsorption (not in thick ascending limb !). In absence of ADH,  is reabsorbed only in the renal cortex preventing disruption of hyperosmolarity in medullary interstitium
• stationary osmotic gradient theory : in the interstitium between cells H₂O osmotically attracted and expelled by mass flow doesn't alter [ions]
• K⁺ reabsorption :
• active process in proximal tubule : 65% (491 mEq/die)
• ascending limb of Henle's loop : 27% (204 mEq/die)
• terminal tract of distal convoluted tubule and cortical collecting duct : 4% (31 mEq/L). Here it can be secreted by aldosterone-dependent intercalated cells.
• HCO₃^- reabsorption : everywhere in the tubule (90% in proximal renal tubule) except that in Henle's loop. Tubular cells are P_{CO2, plasma}- and pH_ECF-sensitive
• contracurrent multiplication renders renal medulla hyperosmotic. The descending limb is H₂O-permeable, while the ascending limb is H₂O-impermeable. In the thick ascending limb the paracellular leakage allows a maximal gradient = 200 mOsm/kg H₂O to be created : starting with an ultrafiltrate at 300 mOsm, kidney can't generate urine with less than 100 mOsm, but addition allows the medullary intersitium to reach 1,200 mOsm/kg H₂O (600 mOsm/kg H₂O from urea + 350 mOsm/kg H₂O from Na⁺ + 350 mOsm/kg H₂O from Cl^-) = maximum urinary concentration (MUC) in humans. The gradient is maintained as v_{tubular output} >> v_{tubular flow}. At the level of distal convoluted tubule and in the first part of collecting duct Na⁺ is reabsorbed (also H₂O upon ADH stimulation), hence generating further hypoosmolar urine that is reabsorbed in the deep portion of collecting duct, near the hyperosmotic interstitium. Cells within this area resist osmotic pressure as also intracellular fluid is hyperosmotic thanks to urea and sorbitol. Urea has the same movement possibilities as H₂O, but with higher rate. Urea can be concentrated up to 600 mOsm (upon ADH stimulation) through a contracurrent exchange system : osmotic outflow in proximal tubule concentrates urea and then let it outflow in the deep area of collecting duct (and even before upon ADH stimulation) increasing osmolarity and partly recirculating. Both arcuated artery (300 mOsm) and efferent arteriole (400 mOsm) are H₂O-permeable but the vertical interstitial gradient is not eliminated as in this contracurrent mechanism v_{horizontal diffusion} >> v_{vertical diffusion} into interstitium. p_{end of vasa recta} ~ k.
• osmole generation = 600 mOsm/die
• forced urinary volume = osmole generation / maximum urinary concentration = 0.5 L / day
• minimum urinary concentration in humans = 50 mOsm/kg H₂O
• maximal urinary volume = osmole generation / minimum urinary concentration = 12 L / die


• autoregulation
• tubuloglomerular feedback : decreased GFR => increased Na⁺Cl^- reabsorption in ascending limb of Henle's loop => decreased [Na⁺Cl^-]_tub sensed by osmoceptors in macula densa => ... =>
• vasodilatation of afferent arteriole
• angiotensin incretion => ... => vasoconstriction of efferent arteriole 10-folds more than afferent arteriole
... => increased GFR
• Bayliss effect : increased flow in arteriole causes vasoconstriction
• tubuloglomerular balance : increased GFR => increased p_cap => increased H₂O and Na⁺Cl^- reabsorption in proximal tubule
Urine : the fluid excreted by the kidneys, passed through the ureters, stored in the bladder, and discharged through the urethra (1 mL/min (1.5 mL/min in males, 1-1.2 mL/min in females) = 1 ml/hr/kg = 40-50 ml/hr = 1,400 mL/die on average: since 180 L/die preurine are filtered, a concentration factor = 180 exists); its constituents and volume vary widely from day to day in order to maintain normal fluid and electrolyte homeostasis.
Examination :
• organolectic characters (naked eye)
• look : limpid or according to diet
• color : pale yellow or according to diet
• smell : according to diet
• chemico-physical characters (indicator dyes)
• urine density (d) = 1.015
• urine osmolality (p) = 50-1,200 mOsm/kg_H2O
• [H⁺] = 3^.10^-2-4^.10^-5 mEq/L => pH = 5-7 (4.5-8)
• molecules (indicator dyes)
• proteinuria = [proteins]_urine : 0-12 mg/dL ; < 150 mg/die (IgG, transferrin, albumin, ...)
• albuminuria
• albumin-creatinine ratio (ACR) < 2.3 mg/mmol
• glycosuria = [Glc]_urine : 0
• ketonuria = [ketones]_urine = 30-70 mg/die
• creatinuria = [creatine]_urine < 100 mg/die = 0.75 mmol/die or < 6% creatininuria
• in pregnants : < 12% creatininuria
• in babies before age 1 may be = creatininuria
• in babies after age 1 < 30% creatininuria
• creatininuria = [creatinine]_urine = 0.8-1.9 g/die or 15-25 mg/kg/die = 0.13-0.22 mmol/kg/die
• azoturia = [N]_urine = 12-30 g/die
• urine urea nitrogen (UUN) = 12-30 ^. 28/60 = 5.6-14 g/die
• hemoglobinuria = [hemoglobin]_urine = 0
• myoglobinuria = [myoglobin]_urine = 0
• uricuria / uricosuria = [uric acid, monosodium or disodium urate, potassium urate, ammonium urate, calcium urate]_urine = 250-750 mg/die in females or 250-800 mg/die in males. Uric acid is more soluble in urine than in water due to presence of urea, proteins, and mucopolysacchardes.
• natriuria = [Na⁺]_urine = 20 mEq/L ; 30-300 mEq / die
• Na⁺ excretion fraction = ([Na⁺]_urine ^. [creatinine]_plasma) / ([Na⁺]_plasma ^. [creatininine]_urine)
• renal failure index = ([Na⁺]_urine^. [creatinine]_plasma) / [creatininine]_urine
• potassiuria = [K⁺]_urine = 40 mEq/L ; 25-125 mg/die = 92 mEq/die
• chloruria = [Cl^-]_urine =
• urinary anion gap (UAG) = [measured cations : Na⁺ + K⁺]_urine - [measured anion : Cl^-]_urine
• phosphaturia = [HPO₄^2- and H₂PO₄^-]_urine = 1 g/die = 32 mmol/die (depending on diet)
• pyrophosphaturia = 4 mg/L
• calciuria = [Ca²⁺]_urine = 100-300 mg/die = 2.5-7.5 mmol/24 hr
• ioduria = [I^-]_urine = 480 mg/die
• total catecholamines < 100-150 mg/die or < 590-885 nmol/die (used in screening patients for pheochromocytoma)
• adrenalin < 20 mg/die or < 109 nmol/die
• noradrenaline < 100 mg/die or < 590 nmol/die
• metanephrine < 1.3 mg/die or < 7 mmol/die
• vanilmandelic or vanillylmandelic acid (VMA) < 9 mg/die or < 45 mmol/die
• 5-hydroxyindoleacetic acid (5-HIAA) = 2-9 mg/die = 10-45 mmol/die
• human chorionic gonadotropin (hCG) : 0
• aldosterone : 5-19 mg/die = 14-53 nmol/die
• cortisol : 20-70 mg/die = 55-193 nmol/die (used in screening patients for Cushing's syndrome)
• [Pb]_urine < 0.08 mg/mL (= 0.39 mmol/L) or < 120 mg/die
• ketonuria = [acetoacetic acid + acetone]_urine = 0
• amylase = 24-76 UI/mL
• cysteinuria = [cysteine]_urine or cystinuria = [cystine]_urine = 0
• hemuria = 0-100 mg/die = 0-1.6 mmol/die
• porphobilinogen = 0
• oxaluria = 8-40 mg/mL = 90-455 mmol/L
• children : urinary oxalate:creatinine molar ratios
• < 1 year : 0.061 (0.015- 0.26) mol/L
• 1-5 years : 0.036 (0.011-0.12) mol/L
• 5-12 years : 0.030 (0.0059-0.15) mol/L
• > 12 years : 0.013 (0.0021-0.083) mol/L
• bilirubinuria = [bilirubin]_urine = 0
• urobilinogenuria = [urobilinogen]_urine < 1 mg / dL or < 1 Ehrlich unit (EU)
• urobilinuria = [urobilin]_urine = 0
• uroporphyrinuria = [uroporphyrin]_urine = 0-30 mg/die or < 36 nmol/die
• coproporphyrinuria = [coproporphyrin]_urine = 50-250 mg/die (0-75 mg/die in babies before 36 kg)
• 17-ketosteroids =

age	males	females
10	1-4 mg/die = 3-14 mmol/die	1-4 = 3-14
20	6-21 = 21-73	4-16 = 14-56
30	8-26 = 28-90	4-14 = 14-49
50	5-18 = 17-62	3-9 = 10-31
70	2-10 = 7-35	1-7 = 3-24

• 17-hydroxycorticosteroids =
• males : 3-10 mg/die = 8.2-27.6 mmol/24 hr
• female: 2.0-8.0 mg/24 hr =  5.5-22 mmol/die
• estriol, total (in pregnancy)
• 30 wks : 6-18 mg/24 hr = 21-62 mmol/24 hr
• 35 wks : 9-28 mg/24 hr = 31-97 mmol/24 hr
• 40 wks : 13-42 mg/24 hr = 45-146 mmol/24 hr
• cross-linked C-telopeptides (U-CTx) CrossLaps (measured in bone collagen equivalent (BCE)) < 407 mg/mL
• urinary sediment after centrifugation (under optical microscope) :
• hematuria = [RBC]_urine = 0-20 / mL or 1-2 ^. 10⁶ RBCs/die
• leukocyturia = [WBC]_urine = 0-20 / mL or 1-4 ^. 10⁶ WBC/die
• [epithelial cells]_urine = 0-40 / mL
• [cylinders]_urine = 0-3 / mL
• [crystals]_urine = 0-40 / mL
• [bacteria]_urine = 0-1000 / mL
• [mycetes]_urine = 0-20 / mL
Urine is a oversaturated solution thanks to inhibitors of crystallization :
• pyrophosphate
• citrate
• Tamm-Horsfall glycoprotein
• GAGs
Miction / uresis / urination / micturition : the discharge or passage of urine.
Web resources : Urine at Weizmann Institute
• ureter / metanephric duct : the fibromuscular tube which conveys the urine from the kidney to the bladder. It begins with the pelvis of the kidney, a funnel-like dilatation, and empties into the base of the bladder, being 16 to 18 inches long. It is divided into
• pars abdominalis
• pars pelvina
• urine spindles : spindle-shaped, urine-filled segments of the ureter due to incomplete occlusion of the ureter during peristalsis.
• (urinary) bladder / vesica urinaria : the musculomembranous sac, situated in the anterior part of the pelvic cavity, that serves as a reservoir for urine; it receives the excretory products of the kidneys through the ureters, and expels them through the urethra
• fundus vesicae urinariae / fundus of urinary bladder / fundus of bladder / infundibulum of urinary bladder : the base or posterior surface of the bladder
• Küss's experiment : injection of a solution of opium or belladonna into the bladder, which produces no symptoms of poisoning and thus proves the impermeability of the bladder epithelium to these substances.
Cell types : urinary epithelium cell
Muscles :
• musculus detrusor vesicae / detrusor muscle of bladder / detrusor urinae / detrusor urinae muscle : the bundles of smooth muscle fibers forming the muscular coat of the urinary bladder, which are arranged in a longitudinal and a circular layer and, on contraction, serve to expel urine
• musculus sphincter vesicae urinariae : sphincter muscle of urinary bladder: a circular layer of fibers surrounding the internal urethral orifice, innervated by the vesical nerve, and acting to close the internal orifice of the urethra.
As urine flows in, the smooth muscle of the bladder relaxes to accommodate 450-500 ml of urine. The urine does not leak from the bladder because of 2 sphincters, the smooth muscle internal sphincter and the skeletal muscle external sphincter. The bladder is innervated by the sympathetic nervous system, which causes the smooth muscle of the bladder to relax and smooth muscle of the internal sphincter to contract, thus promoting the storage of urine in the bladder. The parasympathetic nervous system causes the bladder muscle to contract, thus promoting the emptying of the bladder. The external sphincter is under volitional control : the cerebral cortex, brain stem, and spinal cord are all involved in the process or urination.
• micturition reflex : any of the reflexes necessary for effortless evacuation of urine and subconscious maintenance of continence: vesical contraction following distention of the bladder, vesical contraction evoked by urethral flow, vesical contraction evoked by proximal urethral distention, relaxation of the urethra resulting from running liquid in the urethra, distention of the bladder resulting in relaxation of the external sphincter, relaxation of the proximal urethral smooth muscle by distention of the bladder, and vesical contraction related to running liquid through the urethra.
• bladder reflex : the reflex contracting and emptying of the bladder in response to filling, the first step in the micturition reflex; it can be voluntarily inhibited by impulses from the brain in patients with normal neurological function
• paracystium : the connective and other tissues around the bladder.
• urethra : the membranous canal conveying urine from the bladder to the exterior of the body
• urethra feminina / female urethra / urethra muliebris : a canal about 3.7 cm. long, extending from the neck of the bladder, running above the anterior vaginal wall and piercing the urogenital diaphragm, to reach the urinary meatus
• urethra masculina / male urethra / urethra virilis : a canal extending from the neck of the bladder to the urinary meatus, measuring about 20 cm. in length, and presenting a double curve when the penis is flaccid; it is divided into :
• posterior urethra : the portion of the male urethra extending from the bladder to the bulb, and consisting of the membranous and prostatic parts.
• pars prostatica urethrae masculinae / prostatic urethra
• Henle's sphincter : muscle fibers surrounding the prostatic urethra
• pars intermedia urethrae masculinae / membranous urethra
• anterior urethra / pars spongiosa urethrae masculinae / spongiose urethra / spongy urethra : the portion of the male urethra extending from the bulb to the meatus on the summit of the glans penis, tunneling the corpus spongiosum; it consists of 3 parts:
• bulbous
• pendulous
• glandular part
• urethral lacunae of Morgagni : lacunae urethrales in the male urethra.
Crista urethralis / urethral crest : a prominent longitudinal fold of the mucosa along the posterior wall of the urethra in the female(crista urethralis muliebris and cervical colliculus of female urethra (of Barkow)); and in the male, lying between the prostatic sinuses (crista urethralis virilis)
• lacunae urethrales / urethral lacunae : numerous small depressions or pits in the mucous membrane of the urethra, with their openings usually directed distally. Some contain openings of ducts of the urethral glands
• Schüller's glands / Skene's glands / ductus paraurethrales urethrae femininae
• urethral glands of female urethra / glandulae urethrales urethrae femininae
• functional urethra : > 3 cm in length to be effective, surrounded by smooth muscle fibers from detrusor muscle of bladder and striate muscle fibers from urogenital diaphragm
• musculus sphincter urethrae (membranaceae) / sphincter muscle of urethra : origin, ramus of pubis; insertion, median raphe behind and in front of urethra; innervation, perineal; action, compresses the membranous part of the urethra
• fossa navicularis urethrae [Morgagnii] / navicular fossa of male urethra / crypt, fossa, or fovea of Morgagni : the lateral expansion of the urethra in the glans penis
• valvula fossae navicularis / valve of navicular fossa : a fold of mucous membrane occasionally occurring in the roof of the fossa navicularis of the urethra.
• Guérin's fold : a fold of mucous membrane occasionally seen in the fossa navicularis of the urethra (see also Guérin's sinus)
Cell types :
• urinary epithelial cell / urothelium : 3-7 layers of cells
• surface cell in squamous epithelium of distal urethra
• Brunn's epithelial nests : solid or branched glandlike clusters of transitional epithelium occurring in the lamina propria mucosae of the lower urinary tract.
• basal stem cell in squamous epithelium of distal urethra
For effective containment, urethra has to form a 90-100° angle with the base of the bladder

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