صفحه 1:
®Urine Formation by the Kidneys: Glomerular Filtration, Renal Blood Flow, and Their Control Dr. Mard

صفحه 2:
یس ‎The kidneys serve multiple functions, including the‏ ‎following:‏ © Excretion of metabolic waste products and foreign chemicals © Regulation of water and electrolyte balances ® Regulation of body fluid osmolality and electrolyte concentrations © Regulation of arterial pressure © Regulation of acid-base balance ® Secretion, metabolism, and excretion of hormones © Gluconeogenesis

صفحه 3:
- © Excretion of metabolic waste products and foreign chemicals : include ® urea (from the metabolism of amino acids) © creatinine (from muscle creatine), ® uric acid (from nucleic acids) ® end products of hemoglobin breakdown (such as bilirubin) ® metabolites of various hormones © most toxins and other foreign substances such as pesticides, drugs, and food additives.

صفحه 4:
®Regulation of Water and_ Electrolyte Balances. For maintenance of homeostasis, excretion of water and electrolytes must precisely match intake. = Intake = Output (excret we 4-202 4 6 8 1012 4 Time (cays) © Elsevier. Guyton & Hall: Textbook of Medical Physiology I1e - nwn.studen Cree COA) GPF of teremny ookar taker UD-PeAl (Bran 90 ‏ند‎ 500 eABalky) ow wreray sehen erate oad | cet senkan rear or far ont suckan bow etrconand Pre tar dF ‎noche hehe a noche exer.‏ ما

صفحه 5:
© Regulation of Arterial Pressure Long-term regulation of arterial pressure by excreting variable amounts of sodium and water. Short-term arterial pressure regulation by secreting vasoactive factors or substances, such > Renin angiotensin II

صفحه 6:
® Regulation of Acid-Base Balance The kidneys contribute to acid-base regulation, along with the lungs and body fluid buffers, by excreting acids and by regulating the body fluid buffer stores. The kidneys are the only means of eliminating from the body certain types of acids, such as sulfuric acid and phosphoric acid, generated by the metabolism of proteins.

صفحه 7:
© Regulation of Erythrocyte Production hire erythroperesm RBC production een > Porarwis CRF (hemodialysis)

صفحه 8:
©The kidneys produce the active form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), by hydroxylating this vitamin at the "number 1" position.

صفحه 9:
® Physiologic Anatomy of the Kidneys Location : posterior wall of the abdomen (retroperitoneal) Weight : 150 gr Hilum : entrance of renal pedicles and ureter Fibrous capsule : The kidney is surrounded by a tough, that protects its delicate inner structures.

صفحه 10:
The kidney composed of : two major regions that can be visualized are the outer cortex and the inner region (medulla). Renal pyramids : The medulla is divided into multiple cone-shaped masses of tissue called renal pyramids. The base of each pyramid originates at the border between the cortex and medulla and terminates in the papilla, which projects into the space of the renal pelvis. Renal pelvis : a funnel-shaped continuation of the upper end of the ureter. The outer border of the pelvis is divided into open-ended pouches called major calyces that extend downward and divide into minor calyces

صفحه 11:
Ow Minor calyces : collect urine from the tubules of each papilla. contractile elements : The walls of the calyces, pelvis, and ureter contain contractile elements that propel the urine toward the bladder

صفحه 12:

صفحه 13:
Blood flow: is normally about 22% of the C.O or 1100 ml/min. The renal artery enters the kidney through the hilum and then branches progressively to form : Afferent arteric?e= glomeru®r capillaries Effexgnt arteriole peritubular capillaries

صفحه 14:
GFR Maximum urine flow Normal urine flow Minimum urine flow Renal blood flow 1100 mL/min Renal plasma flow 625 mL/min 125 mL/min 20 mLimi 1 mU/min| 0.4 mL/min ‘© Elsole, Cao: Eso'sIntaratad Physiology - wom sudentconsultcom

صفحه 15:

صفحه 16:
mal circulation is unique-in-that it glomerular and peritubular capillaries, which are arranged (in series), which help regulate the hydrostatic pressure in both sets of capillaries. © High hydro-static pressure in the glomerular capillaries (60 mm Hg) causes rapid fluid filtration, © Whereas a much lower hydrostatic pressure in the peritubular capillaries (about 13 mm Hg) permits rapid fluid reabsorption. © By adjusting the resistance of the afferent and efferent arterioles, the kidneys can regulate the hydrostatic pressure in both the glomerular and the peritubular capillaries, thereby changing the rate of glomerular filtration, tubular reabsorption

صفحه 17:
۳ 89 tional L ~~ Kidney Each kidney (1 million nephrons) Each nephrons capable of forming urine. The kidney cannot regenerate new nephrons Therefore, with renal injury, disease, or normal aging, there is a gradual decrease in nephron number. After age 40, the number of functioning nephrons usually decreases about 10 per cent every 10 years. Each nephron contains : (1)The glomerulus (2)a long tubule in which the filtered fluid is converted into urine on its way to the pelvis of the kidney

صفحه 18:
e glomerulus contains a network of branching and anastomosing glomerular capillaries that, compared with other capillaries, have high hydrostatic pressure (60 mm Hg). The glomerular capillaries are covered by epithelial cells, and the total glomerulus is encased in Bowman's capsule. Fluid filtered from the glomerular capillaries flows into Bowman's capsule and then into the proximal tubule

صفحه 19:
Thick segment of ascending limb Thin segment of ascending limb Descending limb © Elsevier. Guyton & Hall: Textbook of Medical Physiology 11e - www.studentconsult.com

صفحه 20:
وب سس Bladder Figure 26-7. Innervation af the urinary bladder

صفحه 21:
Pain sensation in ureter © Reflex. The ureters are well supplied with pain nerve © fibers. When a ureter becomes blocked (e.g., by a ureteral stone), intense reflex constriction occurs, which is associated with severe pain. Also, the pain impulses cause a sympathetic reflex back to the kidney to constrict the renal arterioles, thereby decreasing urine output from the kidney. This effect is called the ureterorenal reflex and is important for preventing excessive flow of fluid into the pelvis of a kidney with a blocked ureter.

صفحه 22:
vation of the Bladder.___ ۳ © principal nerve supply of the bladder-the pelvic nerves, which connect with the spinal cord through the sacral plexus, ($2 and $3) The sensory fibers detect the degree of stretch in the bladder wall. Stretch signals from the posterior urethra are especially strong and are mainly responsible for initiating the reflexes that cause bladder emptying. The motor nerves transmitted in the pelvic nerves are parasympathetic fibers. In addition to the pelvic nerves, two other types of innervation are important in bladder function. Most important are the skeletal motor fibers transmitted through the pudendal nerve to the external bladder sphincter. ‘These fibers are somatic nerve fibers that innervate and control the voluntary skeletal muscle of the sphincter. Also, the bladder receives sympathetic innervation from the sympathetic chain through the hypogastric nerves, connecting mainly with the L2 segment of the spinal cord. These sympathetic fibers stimulate mainly the blood vessels and have little to do with bladder contraction. Some sensory nerve fibers also pass by way of the sympathetic nerves and may be important in the sensation of fullness and, in some instances, pain.

صفحه 23:
Volume (milliliters) Figure 26-8. A normal cystometrogram, showing also acute pres- sure waves (dashed spikes) caused by micturition reflexes.

صفحه 24:
e 26-8 shows the approximate intravesicular pressure as the bladder fills with urine. When there is no urine in the bladder, the intravesicular pressure is about 0, but by the time 30 to 50 milliliters of urine have collected, the pressure rises to 5 to 10 centimeters of water. © Additional urine—200 to 300 milliliters—can collect with only a small additional rise in pressure; this constant level of pressure is caused by intrinsic tone of the bladder wall. Beyond 300 to 400 milliliters, collection of more urine in the bladder causes the pressure to rise rapidly. © Superimposed on the tonic pressure changes during filling of the bladder are periodic acute increases in pressure that last from a few seconds to more than a minute. The pressure peaks may rise only a few centimeters of water or may rise to more than 100 centimeters of water. These pressure peaks are called micturition waves in the cystometrogram and are caused by the micturition reflex.

صفحه 25:
As the bladder fills, many superimposed micturition contractions begin to appear, as shown by the dashed spikes. They are the result of a stretch reflex initiated by sensory stretch receptors in the bladder wall, especially by the receptors in the posterior urethra when this area begins to fill with urine at the higher bladder pressures. ® Sensory signals from the bladder stretch receptors are conducted to the sacral segments of the cord through the pelvic nerves and then reflexively back again to the bladder through the parasympathetic nerve fibers by way of these same nerves. ® When the bladder is only partially filled, these micturition contractions usually relax spontaneously after a fraction ® of a minute, the detrusor muscles stop contracting, and pressure falls back to the baseline ® As the bladder continues to fill, the micturition reflexes become more frequent and cause greater contractions of the detrusor muscle. ® Once a micturition reflex begins, itis “self-regenerative.” That is, initial contraction of the bladder activates the ® stretch receptors to cause a greater increase in sensory impulses from the bladder and posterior urethra, which ® causes a further increase in reflex contraction of the bladder; thus, the cycle is repeated again and again until ® the bladder has reached a strong degree of contraction. ® Once the micturition reflex becomes powerful enough, it causes another reflex, which passes through the pudendal ٩ “nerves to the external sphincter to inhibit it. If this inhibition is more potent in the brain than the voluntary ® constrictor signals to the external sphincter, urination will occur. If not, urination will not occur until the bladder fills still further and the micturition reflex becomes more powerful

صفحه 26:

صفحه 27:
known as the macula densa © Distal tubule : Beyond the macula densa, fluid enters the distal tubule, which, like the proximal tubule, lies in the renal cortex. This is followed by the connecting tubule and the cortical collecting tubule, which lead to the cortical collecting duct. ۰ © The initial parts of 8 to 10 cortical collecting ducts join to form a single larger collecting duct that runs downward into the medulla and becomes the medullary collecting duct. © The collecting ducts merge to form progressively larger ducts that eventually empty into the renal pelvis through the tips of the renal papilla In each kidney, there are about 250 of the very large collecting ducts, each of which collects urine from about 4000 nephrons.

صفحه 28:
egional Differences in Nephron Structure (Length of Henle & the vascular structures) Cortical : 1. Glomeruli located in the outer cortex 2. They have short loops of Henle that penetrate only a short distance into the medulla 3. The entire tubular system is surrounded by an extensive network of peritubular capillaries Juxtamedullary Nephrons (20 to 30 % of the nephrons) : 1, glomeruli that lie deep in the renal cortex near the medulla 2.These nephrons have long loops of Henle that dip deeply into the medulla 3. long efferent arterioles extend from the glomeruli down into the outer medulla and then divide into specialized peritubular capillaries called vasa recta (this specialized network of capillaries in the medulla plays an essential role in the formation of a concentrated urine).

صفحه 29:
© Elsevier Lid. Berne et al: Physioloay SE www.studentconsult.com ‘ynpeui seuuy jppew ۵

صفحه 30:
© Urine Formation Results from Glomerular Filtration, Tubular Reabsorption, and Tubular Secretion © The rates at which different substances are excreted in the urine represent the sum of three renal processes, shown in © (1) glomerular filtration © (2) reabsorption © (3) secretion Expressed mathematically: Urinary excretion rate= Filtration rate- Reabsorption rate + Secretion rate

صفحه 31:
4. Filtration 2, Reabsorption 3, Secretion 4. Excretion Urinary excretion ‎exoretica rote= Pirotica rote- Reubsorpicg rate + Georetiva rate‏ و(

صفحه 32:
Ultrafiltation : © Urine formation begins when a large amount of fluid that is virtually free of protein is filtered from the glomerular capillaries into Bowman's capsule. Most substances in the plasma, except for proteins, are freely filtered, so that their concentration in the glomerular filtrate in Bowman's capsule is almost the same as in the plasma.

صفحه 33:
Fitration only Filtration, partal reabsorption Substance A Substance B vine Urine C. Fitton, complete Fitaion, secretion reabsorption ‘Substance C ‘Substance D urine Urine

صفحه 34:
IA is freely filtered by the glomeru ut is neither reabsorbed nor secreted. Therefore, its excretion rate is equal to the rate at which it was filtered (such as creatinine) Panel B, the substance is freely filtered but is also partly reabsorbed from the tubules back into the blood (rate of urinary excretion < rate of filtration): electrolytes In this case, the excretion rate is calculated as the filtration rate minus the reabsorption rate. Panel C, the substance is freely filtered at the glomerular capillaries but is not excreted (comp[letly absorbed) shuch as : nutritional substances (amino acids and glucose) Panel D is freely filtered at the glomerular capillaries and is not reabsorbed, but additional quantities of this substance are secreted from the peritubular capillary blood into the renal tubules (organic acids and bases. The excretion rate in this case is calculated as filtration rate plus tubular secretion rate.

صفحه 35:
8 on, absorpt Different Substances In general, tubular reabsorption is quantitatively more important than tubular secretion in the formation of urine, but secretion plays an important role in determining the amounts of K and H ions Most substances that must be cleared from the blood, especially the end products of metabolism such as urea, creatinine, uric acid, and urates, are poorly reabsorbed and are therefore excreted in large amounts in the urine.

صفحه 36:
\re Large Amounts of S absorbed by the Kidneys? One might question the wisdom of filtering such large amounts of water and solutes and then reabsorbing most of these substances. 1. One advantage of a high GFR is that it allows the kidneys to rapidly remove waste products from the body that depend primarily on glomerular filtration for their excretion. 2. A second advantage of a high GFR is that it allows all the body fluids to be filtered and processed by the kidney many times each day. Because the entire plasma volume is only about 3 liters, whereas the GFR is about 180 L/day, the entire plasma can be filtered and processed about 60 times each day. This high GFR allows the kidneys to precisely and rapidly control the volume and composition of the body fluids.

صفحه 37:
1 21105 Filtrate composition s Free from proteins and devoid of cellular elements, including red blood cells. The concentrations of other constituents of the glomerular filtrate, including most salts and organic molecules, are similar to the concentrations in the plasma. Exceptions for calcium and fatty acids because of almost one half of the plasma calcium and most of the plasma fatty acids are bound to proteins

صفحه 38:
low GFR is determined by: )1( 200 ۲ (2) the capillary filtration coefficient (Kf) [the product of the permeability x A] K, of glomerular capillaries=400 other capillaries

صفحه 39:
Efferent Glomerular ‘oncotic pressure (32 mm Hg) Bowman's capsule pressure (18 mm Hg) Glomerular hydrostatic pressure (60 mm Hg) Afferent arteriole Net filtration pressure (10mm Hg)

صفحه 40:
_ the average adult human, the GFR is = out 125 ml/min, or 180 L/day. The fraction of the renal plasma flow that is filtered (the filtration fraction) averages about 0.2; this means that about 20 % of the plasma flowing through the kidney is filtered through the glomerular capillaries Filtration fraction : GFR/Renal plasma flow

صفحه 41:
merular Capillary Membrane The glomerular capill membrane i: similar to that of other capillaries except that it has three (instead © the usual two) major layers: © Endothelium © A basement membrane * A llayer of epithelial cells (podocytes, Alfeent arteriole Etlerent arteriole Together, these layers make up the filtration barrier, which, despite the three layers, filters Several hundred times as much water anc ‏مهو‎ ‎solutes as the usual capillary membrane. ‏تست‎ membrane Ultra-filtration : Even with this high rate of filtration, the glomerular capillary membrane normally prevents 8 ‏هه‎ ‎filtration of plasma proteins. Endothelin

صفحه 42:
Lumen of Bowman's capsule Basement membrane Filtration slit ~ Capillary endothelium Filtered material Capillary lumen Bowman's capsule epithelium endothelium 1 Eisele, Cano: Esove'sIntearatad Physiology - won sudentconsuitcom

صفحه 43:
Their Size The glomerular capillary membrane is thicker than most other capillaries, but it is also much more porous and therefore filters fluid at a high rate. Despite the high filtration rate. the alomerular filtration barrier is selective in deterr Table 26-4 their size and_ Filterability of Substances by Glomerular Capillaries Based ‘on Molecular Weight Substance Molecular Weight Filterability Water 18 1.0 Sodium 23 1.0 Glucose 180 1.0 Inulin 5500 1.0 Myoglobin 17,000 0.75 Albumin 69,000 0.005

صفحه 44:
© The molecular diameter of the plasma, protein albumin is only about 6 nm, whereas the pores of the glomerular membrane are thought to be about 8 nanometers © Albumin is restricted from filtration, however, because of its negative charge. and the electrostatic repulsion exerted by negative charges of the glomerular capillarv wall proteoalvcans —Poiyeationie dextvan Neutral dextran —Polyanionic dextran 18 2 26 30 4 38 42 Efective molecular radius (A)

صفحه 45:
In certain kidney diseases, the negative charges on the basement membrane are lost even before there are noticeable changes in kidney histology, a condition referred to as minimal change nephropathy. As a result of this loss of negative charges on the basement membranes, some of the lower-molecular-weight proteins, especially albumin, are filtered and appear in the urine, a condition known as proteinuria or albuminuria.

صفحه 46:
GFR is determined by (1) the sum of the hydrostatic and colloid osmotic forces across the glomerular membrane, which gives the net filtration pressure, and (2) the glomerular capillary filtration coefficient, Kf. Expressed mathematically, the GFR equals the product of Kf and the net filtration pressure: * GFR = Kf “Net filtration pressure

صفحه 47:
hy drostatic and colloid osmotic 0۳06 or oppose filtration across the glomerular eapillaries. © These forces include (1) hydrostatic pressure inside the glomerular capillaries (glomerular hydrostatic pressure, PG), which promotes filtration © (2) the hydrostatic pressure in Bowman's capsule (PB) outside the capillaries, which opposes filtration © (3) the colloid osmotic pressure of the glomerular capillary plasma proteins (mG), which opposes filtration © (4) the colloid osmotic pressure of the proteins in Bowman's capsule (mB), which promotes filtration. (Under normal conditions, the concentration of protein in the glomerular filtrate is so low that the colloid osmotic pressure of the Bowman's capsule fluid is considered to be zero.) © The GFR can therefore be expressed as GFR = K; x (Pg — Pp - 10 + Tp)

صفحه 48:
® Increased Glomerular Capillary Filtration Coefficient Increases GFR K, = GFR/Net filtration pressure

صفحه 49:
Pressure Decreases GFR In certain pathological states associated with obstruction of the urinary tract, Bowman's capsule pressure can increase markedly, causing serious reduction of GFR. For example, precipitation of calcium or of uric acid may lead to "stones" that lodge in the urinary tract, often in the ureter, thereby obstructing outflow of the urinary tract and raising Bowman's capsule pressure. This reduces GFR and eventually can damage or even destroy the kidney unless the obstruction is relieved.

صفحه 50:
Filtration traction ‘osmotic pressure (mm Hg) Glomerular colloid Filtration fraction 8 8 8 8 م 88 2016086000 ‏المت‎ 10 end Distance along end glomerular capillary

صفحه 51:
Glomerular filtration ‎SS‏ ۰ وراد ‎ ‎ ‏كاهش ‎baw 5 GFR‏ #تنكى متوسط وابران م : افزایش ‎oy GFR‏ ‎ ‏ناشی از افزایش فشار هیدروستاتیک ‎ ‎: ‏شدید وابران‎ x ‏از افزایش‎ cb GFR ‏اسمزی کلوئیدی‎ ‎ ‎

صفحه 52:
Ow © Increased Glomerular Capillary Colloid Osmotic Pressure Decreases GFR

صفحه 53:
سا سا مسا نبا ‎be werd phowa volo! vows pressure unt‏ © ‎by he dower vapikries (Aivvioa Previn).‏ اسلا متام ‎fre Prectca of‏ )©( ‎pressure, which tr Karst‏ وی لمات بای لو ها مور جوم تور لاه ام له ‎Coorecsn| the‏ ‎BPR‏ یت ‎(see‏ سم وه تاحفص لو ‎he phswa protic‏ موه تج مه( ما با موه لس سا مه مس ‎dePoed ar OP Rlreud phewa Pow, ke Piratoo‏ جز ما مها با مهب( ۱ و ۰ ای لا مت تن ‎(Por excep, 0 reduction fr read pla Pus‏ سنا ام لم پل ‎ether by raster, (BOP or by‏ لوا له و موی لاه نوی لصو ول و تفت نوات رو ما ما و ول ‎(BPR wand‏ لا وا ی ‎of‏ راومه ۴) ‎reduce (BPR. (Por thts reac, changes tr read blood Aw coo Pec‏ حسم جلها وهات 5 رجصی ری لول بط و می تلا رقف ع مصجصام هذا خام ومتجصةا عصبطا د بنيطة! لعمصاط أددمر ودتصصصصه جلا( موه و ‎eved wih‏ هجو ,20 و ماه ماه ‎tee the qoxeerdar coptlary colo oswote pressure ced bees‏ ‎ybweruke hydrostats pressure, 0 gredier rate oP bod Plu tac the qbxver dus trade to morse (BPR, od 0 bier rate of‏ bod Phau ‏جد حايص صاصتمال جا حفط‎ decrease BER,

صفحه 54:
out 60 mm under normal conditions. Changes in glomerular hydrostatic pressure serve as the primary means for physiologic regulation of GFR. Increases in glomerular hydrostatic pressure raise GFR, whereas decreases in glomerular hydrostatic pressure reduce GFR. e ‏مت یت‎ hydrostatic pressure has been estimated to © Glomerular hydrostatic pressure is determined by three variables, each of which is under physiologic control: (1) arterial pressure, (2) afferent arteriolar resistance, and (3) efferent arteriolar resistance.

صفحه 55:
ا - Factors That Can Decrease the Glomerular Filtration Rate Physiologic/Pathophysiologic Causes Renal disease, diabetes mellitus, hypertension Urinary tract obstruction (e.g... kidney stones) 4 Renal blood flow, increased plasma proteins 4 Arterial pressure (has only small effect due to autoregulation) 4 Angiotensin II (drugs that block angiotensin II formation) T Sympathetic activity, vasoconstrictor hormones (e.g. norepinephrine, endothelin) R (GFR) Physical Determinants* LK) >1GFR 1 ‏ل + و۲‎ 6 176 ‏كه ل‎ ل ل ع وم ل مج مه 1 LRE > LPG TR»A> IPG * Opposite changes in the determinants usually increase K,, glomerular filtration coetficient: P,, Bowman's capsule hydrostatic pres- sure; X;, glomerular capillary colloid csmotic pressure; Po, glomerular capil- lary hydrostatic pressure:A,. systemic arterial pressure: R,. efferent arteriolar resistance; R afferent arteriolar resistance.

صفحه 56:
© Renal Blood Flow ®Ina ‏و‎ man, the combined blood flow through both kidneys is about 1100 ml/min (22 % of the CO). Considering the fact that the two kidneys constitute only about 0.4 % of the TBW, one can readily see that they receive an extremely high blood flow compared with other organs. Aims of the highly BF : © Supplies nutrients and removes waste products © The purpose of this additional flow is to supply enough plasma for the high rates of glomerular filtration that are necessary for precise regulation of body fluid volumes and solute concentrations. As might be expected, the mechanisms that regulate renal blood flow are closely linked to the control of GFR and the excretory functions of the kidneys.

صفحه 57:
© The kidneys oxygen consumption=2 times of brain © Thus, the oxygen delivered to the kidneys far exceeds their metabolic needs © A large fraction of the oxygen consumed by the kidneys is related to the high rate of active sodium reabsorption by the renal tubules. © Therefore, renal oxygen consumption varies in proportion to renal tubular sodium reabsorption, which in turn is closely related to GFR and the rate of sodium filtered.

صفحه 58:
‘Sodium reabsorption (mEq/min per 100 ‏و‎ kidney weight) 10 15 20 5 95 8 86 0 ۳

صفحه 59:
© Determinants of Renal Blood Flow © Renal blood flow is determined by the pressure gradient across the renal vasculature (the difference between renal artery and renal vein hydrostatic pressures), divided by the total renal vascular resistance: (Renal artery pressure — Renal vein pressure) Total renal vascular resistance

صفحه 60:
of the renal major segments: interlobular arteries, afferent arterioles, and efferent arterioles. © Resistance of these vessels is controlled by the sympathetic nervous system, various hormones, and local internal renal control mechanisms, as discussed later. © An increase in the resistance of any of the vascular segments of the kidneys tends to reduce the renal blood flow, whereas a decrease in vascular resistance increases renal blood flow if renal artery and renal vein pressures remain constant

صفحه 61:
ough changes in arterial pressure on renal blood flow, ©The kidneys have effective mechanisms for maintaining renal blood flow and GFR relatively constant over an arterial pressure range between 80 and 170 mm Hg, a process called autoregulation (myogenic and metabolic regulations). © This capacity for autoregulation occurs through mechanisms that are completely intrinsic to the kidneys

صفحه 62:
— = سا _ ۶ © Blood Flow in the Vasa Recta of the Renal Medulla Is Very Low Compared with Flow in the Renal Cortex © Blood flow in the renal medulla accounts for only 1 to 2 % of the total renal blood flow.

صفحه 63:
9 Physiologic Control of Glomerular Filtration and Renal Blood Flow © The determinants of GFR include 1. the glomerular hydrostatic pressure 2. and the glomerular capillary colloid osmotic pressure. These variables, in turn, are influenced by 1. the sympathetic nervous system 2. hormones and autacoids (vasoactive substances that are released in the kidneys and act locally)

صفحه 64:
pathetic_Nervo Decrease 5 Strong activation : constrict the renal arterioles and 1. decrease renal blood flow and 2. GFR. Moderate or mild has little influence on renal blood flow and GFR. Under normal condition, sympathetic tone appears to have little influence on renal blood flow.

صفحه 65:
. Norepinephrine . Epinephrine . Endothelin Constrict Renal Blood Vessels and. Decrease GFR. ده تب NE and Epinephrine (severe hemorrhage) constrict afferent and efferent arterioles GFR and ‏ی‎ ‎RBF Endothelin (vascular injury, such as toxemia of pregnancy, acute renal failure, and chronic ro renal vasoconstriction and GFR

صفحه 66:
aglandins and Brady Increase GFR. PGE2 and PGI2 and bradykinin cause 1. Vasodilation 2. increased renal blood flow 3. and GFR These agents # sympathetic effect Under stressful conditions, such as volume depletion or after surgery, the administration of nonsteroidal anti-inflammatory agents, such as aspirin, that inhibit prostaglandin synthesis may cause significant reductions in GFR.

صفحه 67:
۱ 6۳8 ۴

صفحه 68:
Autoregulation of GFR and Renal Blood Flow Feedback mechanisms intrinsic to the kidneys normally keep the RBF and GFR relatively constant, despite marked changes in arterial blood pressure. This relative constancy of GFR and renal blood flow is referred to as autoregulation.

صفحه 69:
1 In the kidneys, the normal blood flow is much higher than that required for these functions. The major function of autoregulation in the kidneys is to maintain a relatively constant GFR and to allow precise control of renal excretion of water and solutes

صفحه 70:
تسه سس ‎igure 26-16 Autoregulation of renal blood flow and glomerular‏ ‎filtration rate but lack of autoregulation of urine flow during‏ changes in renal arterial pressure. 1600 100 ¢ ‏مب‎ 1 ‏مه و‎ ORE =e 2 se Feral boos fow 38 fae 5 8 5 8 ae 85 ‏م‎ ‎ge ‎5 2 50 100 150 200 Arterial pressure (mm Hg) ‎a a a‏ دس ی ی ی ار و یس ‎ ‎

صفحه 71:
e GFR __ normally remains autoregulated (that is, remains relatively constant), despite considerable arterial pressure fluctuations that occur during a person's usual activities (a decrease in arterial pressure to as low as 75 mm Hg or an increase to as high as 160 mm Hg changes GFR only a few percentage points).

صفحه 72:
nee of = Preventing Extreme Changes in Renal Excretion The autoregulatory mechanisms of the kidney are not 100 per cent perfect, but they do prevent potentially large changes in GFR and renal excretion of water and solutes that would otherwise occur with changes in blood pressure.

صفحه 73:
ormally, GFR is about 180 L/day and tubular reabsorption is 178.5 L/day, leaving 1.5 L/day of fluid to be excreted in the urine. In the absence of autoregulation, a relatively small increase in blood pressure (from 100 to 125 mm Hg) would cause a similar 25 per cent increase in GFR (from about 180 to 225 L/day). If tubular reabsorption remained _constant_at_178.5 L/day, this would increase the urine flow to 46.5 L/day

صفحه 74:
ut in reality, such a change in arterial pressure exerts much less of an effect on urine volume for two reasons: (1) renal autoregulation prevents large changes in GFR that would otherwise occur, and (2) there are additional adaptive mechanisms in the renal tubules that allow them to increase their reabsorption rate when GFR rises, a phenomenon referred to as glomerulotubular balance

صفحه 75:
@ of Tubuloglomerular in Autoregulation of GFR © To perform the function of autoregulation, the kidneys have a feedback mechanism that links changes in NaCl concentration at the macula densa with the control of renal arteriolar resistance. This feedback helps ensure a relatively constant delivery of NaCl to the distal tubule and helps prevent spurious fluctuations in renal excretion that would otherwise occur.

صفحه 76:
juxtaglomerular com sists of 1- macula densa cells in the initial portion of the distal tubule and 2- juxtaglomerular cells in the walls of the afferent and efferent arterioles. The macula densa is a specialized group of epithelial cells in the distal tubules that comes in close contact with the afferent and efferent arterioles. The macula densa cells contain Golgi apparatus, which are intracellular secretory organelles directed toward the arterioles, suggesting that these cells may be secreting a substance toward the arterioles.

صفحه 77:
se a lation of Afferent Arterioles Increased Renin Release and one ae CO ae ‏تب‎ henge: in olume ivery to the distal tugule. flow rate in the logs Henle reab¥orption NaCl NaCl at the macula densa cells initiates a signal from the macula densa that has two effects

صفحه 78:
re. giotensinogaa=a=> angiot angiotensin II Angiotensin II constricts the efferent arterioles, thereby increasing Pc and returning GFR toward normal.

صفحه 79:
Glomerular ‏هه‎ ۳9 ‏ل‎ ‘membrane tubule © Elsevier Guyton & Hall: Textbook of Medical Physiology 11¢ - wwvr.studentconsult.com

صفحه 80:
© Elsevier La, Bere ota: Physioloay SE ww. studentconsult.comt

صفحه 81:
fa lee 0 Glomerular hydrostatic 9 ‏تک‎ pressure ~ 1 وعه 37 4 Angiotensin it ۱ Etferent Aferent ۸ ۱ resistance resistance © Elsevier. Guyton & Hall: Textbook of Medical Physiology 11¢ - www.studentconsult.com

صفحه 82:
سح oa ter During Renal Hypoperfusion As discussed earlier, a preferential constrictor action of angio II on efferent arterioles helps prevent serious reductions in Pc and GFR when renal perfusion pressure falls below normal. The administration of drugs that block the formation of angio II (inhibitors) or that block the action of angio II (angio II antagonists) causes greater reductions in GFR than usual when the renal arterial pressure falls below normal. Therefore, an important complication of using these drugs to treat patients who have hypertension because of renal artery stenosis (partial blockage of the renal artery) is a severe decrease in GFR that can, in some cases, cause acute renal failure.

صفحه 83:
Nevertheless, angiotensin II-blocking drugs can be _ useful therapeutic agents in many patients with hypertension, congestive heart failure, and other conditions, as long as they are monitored to ensure that severe decreases in GFR do not occur.

صفحه 84:
High Protein Intake and Increased Blood Glucose

صفحه 85:
Urinary excretion = Glomerular filtration - Tubular reabsorption + Tubular secretion

صفحه 86:
Tubular Reabsorption Is Selective and Quantitatively Large Filtration = Glomerular filtration rate* Plasma concentration

صفحه 87:
Table 2-4 Filtration, Reabsorption, and Excretion Rales of Different Substances by the Kidneys ‘Ament Filtered ‘Amount Reabsortiod ‘Amount Exereted ‘Ye of Filtered Load Reabsorbed Glucose (gay) ۳ 180 0 ۳ Bicarbonate (mEqiday) 4200 4318 2 5009 Sodium (mEqiday) 25540 ‏اد‎ 1 ous Chloride (mEqldey] 19.40 19260 8 91 Potassinm (mEday) 156 64 2 11 tea (gia) 468 24 BA 3 Creatinine (giday) 18 1 18 0

صفحه 88:
Peritubular Tubular ۱33 ‏ال‎ ‎cells ۷‏ مامه ‎Lumen‏ ‎ih oe Peraceltier ‎ow, ۳ 0 ‏م‎ ‎Active ‏كو‎ ‎& Passive (difusion) Sales ‎Dsmosie¢— H,0‏ هد ‎ ‎REABSORPTION ‏مسج‎ ‎۱ ‎Figure 27-4 ‎Reabsorptian of filtered water and solutes from the tubular humen across the tabalar epithelial cll through the renal interstitium, and back into the blood. Solute: are transported through the cells (trans- cellar route) by passive diffusion or active transport, or betwosn the cells (paracellular route) by diffusion, Water is transported through the cells and between the tubular cells by osmosis. Trans- port of water and soluves from the interstdial uid into the per- ‘ubuler capillaries occurs by ultsaflration (bulk flow).

صفحه 89:
Interstitial Tubular Tubular fluid cells. lumen, Co-transport ay Glucose Na* eon, Amino ai —_ <>" -70mV - Counter-transport Figure 27-3 ‘Mechanisms of secondary active transport. The upper cell shows the

صفحه 90:
900. 800. Transport maximum /Reabsorption Glucose filtered load, reabsorption ‘or excretion (mg’min) 100. ‎B00 700 B00‏ 500 400 300 200 100 و ‎Plasma glucose concentration‏ تن ‎Figure 27-4 ‎Relations among the fitered load of glucose. the rate of glucose reabsorption by tho ronal twbules and the rate of glucose exeration inthe urine, The ransport main fs the ual ext ut whlch glucose can be reabsorbed from the tubules. The dhreshold for iEhicore rofore tothe fltrad load of glucose at which alacose frst ‘opine to be excreted in the urine ‎

صفحه 91:
Substance Transport Maximum ‎mgimin‏ 375 میاه ‎Phosphate ‏تاه وله‎ Sulfate 01.06 mMimin ‘Amino acids 15 m/min Urate 15 mgimin Lactate 75 mgmin Plasma protein 306 ‏متصاعس‎ ‎Transport Maximums for Substances That fre Actively Secreted. Substances that are actively secreted also exhibit transport maximums as follows: ‎Substan Transport Maximum ‎ ‎Creatinine 16 mpmin Para-aminchippurie acid 90 mp/min ‎

صفحه 92:
Na* reabsorption 4 HO reabsorption 1 | Lumen Luminal Luminal CE negetive urea Ares ‏مه‎ ٩ ‏سس‎ ‎Passive Cr Pastive urea reabsorption reabsorption Figure 27-5 Mechenisas by which water, chloride, and urea reabsorption are coupled with sodiam reabsorption.

صفحه 93:
Collulor ultrastructure and primary troneport charscteristies of the proximal tubule. The proximal tubules renbsorb about 65 per cent Of the tltered sedium, chloride, biearbonste, and potassium and sseontially all the filtered glucore and amino acids, The prosimal {nibs also secrete organic acids. bases, ané hyclrogen ions into the tubular lumen,

صفحه 94:
100 Creatinine, Nav 20 40 6080 % Total proximal tubule length ابم plasma concentration °

صفحه 95:
Loop oP Wee Thick ascending Toop of Hone Collar uluestructure and vansport characteristics of the thin | oop of Henle (tp) and ie Ihek ascending sexe nt of the loop of Heute (bo) The descending pat the tia sexe tthe lop of Heals ily peeneable to water and moderately Permeable tonto! welts bul her few mitochondria and ite ene [Stne reorption The thc atcending ly of the lonp of Neale ‏ب كه بد لي‎ the flier lone sedan ‏باه‎ ‎nd potest, as well 9 large emis of eae, bieareonats {nd mngnestum, Ths spre also secretes hysrogen fons imo the tabular ten

صفحه 96:
‎Renal‏ حك ‎intact Tubular‏ ‎cial all‏ ‏یوب ۳ 0 ‎ ‎= ‎© ‎Loop diuretics Furosemide *Ethacrynie acid Bumetanide ‏مه بو ‎Mechasiins of nom, chliie, and pansion ‏موه‎ ithe thick ascending lop of Henle The soda petasism A Pee pam Inthe howlnter! cll membrane. mantnine 8 (ow toc: ar featiam conesntatin anda negate eer potent thee “Tho Iseium, 2 chloride, -potassim c-tansporer i thofeminal ‏هو‎ vauspocs these eee fom om the tba fale fate ‘hocells sig ho ‏جات هناد‎ fleas by dito of sodium, ‏میات هه ول‎ xraieat into the cells Solari ale ‘ansportd ot the tua cellby sodium ogen eousterrans fot. the pontine charge (28 mV) of the tabula hc eae To frome mt othe interstt!H vate parce pth

صفحه 97:
Renal Tubular interstitial Tubular humen ‘ie calls tom Oppronertely G% oP te Phered bed oP 9 ‎te redeorbed i fe Poly -‏ باه 0ك ‎cid ‏سلطا‎ oo ‎over‏ رس ‎ ‎Thiazide diuretics: ‎Figure 27-10 ‎chloride transport in the early dtl tubo‏ موه ام دوس ‎Sodiun and chloride me transported from the tubular Inner Into‏ ‎the cell by co-iransporter tt le Inkibited by thlazde diuretics‏ ‎Sodium ie pumped out of tho eal by socium potassium ATPace and‏ ‎‘hlorige diffuse nto the interstitial eid va chloride chaanela‏ ‎

صفحه 98:
‎tubule‏ ما رارمع ‎

صفحه 99:
Mecha ‏وی‎ ‘mela collating Set Tho mein clletng duce actly Feabsorb sium and secrete nrogea fons and are permeable © ‘on hi is oubwotbed la thew tubular sine Ts absorp ono tern esl cing dt contro he et ‘uation of antidiuretic

صفحه 100:
0 luidiplaema concentration Proximal tubule 1 Hone 1 tubule mbit t Figure 27-44 (Changes in average concentrations of diferent substances at difer- {ont points nthe tubal system rolative tothe concentration of that Subance in the psa and inthe glomerular fiat. vakteof 10 Indicates thatthe concentration ofthe subwiance Inthe tuba Bid {sth same the concentration of that substance inthe plasms, ‘Vales love Li indicate thot the substance = eahsorbed more avidly Wan ater, whereas valves bv (ince tht he nab Stance ie reebeorbod ts lssr extent than water orf eerste into ‏نا‎

صفحه 101:
‎Tubular Tubular‏ ی ‎capillary fuid cells lumen‏ ‎ ‎ ‎Wer ‎۳ ‎Netreabsorption 0 ۳ 0 ‎is ‎Figure 27-15, ‎Summary of the hydrostatic and colloid osmotic forces that deter- imine fuid reabsorption by the peritubular capillaries. The aumeri= cal values shown are estimates of the normal values for humans. The net reabsomptive pressure is normally about 10 mm Hg. causing fluid and sohutes to be reabsorbed into the peritubular capillaries as they fare trarsported across the ronal tubular calls. ATP. adonosins iphospliate; P,, peritubular capillary Lydrostatie pressure; Py inter stitial fluid hydrostatic pressare: ™, peritubular capillary colloid osmotic pressure: My. interstitial uid colloid osmotic pressure,

صفحه 102:
Factors That Can Influence Peritubular Capillary Reabsorption TP. 4 Reabsorption ۰۱ ‏رز‎ ‎۰ ‏1ج 1 زا‎ ۱ T ‏دیع‎ T Reabsorption Tmotn ‏1ب ۲۲۲ و‎ TK, > T Reabsorption ۳: peritubular capillary hydrostatic pressure: Ra and Re, afferent and elfer- ent arteriolar resistances, respectively: ‏يج‎ peritubular capillary colloid osmotic pressure; Xa, arterial plasma colloid osmotic pressure; FF, filtration traction; K,, peritubular capillary filtration coetticient,

صفحه 103:
‎incensed‏ دب ‎‘backloak‏ > ‎

صفحه 104:
Normal 0 ‘tas cals “Fiure 27-16, sora sonditins ep) and during doctewsal porta ‏ری‎ ‘Sronini Searhces oo ‏اس سا‎ te ‏ز‎

صفحه 105:
تا 1 NaCl, HAO reabsorption, 1 K”soeretion 1 NaC. HO reabsorption, THY secretion 70 reabsorption 4 NaCl reabsorption 4 PO; reabsorption, T Co” reabsorption | Table 27-3 Hormones that Regulate Tabular Reabsorption Hormone Sito of Aetion Aldosterone Collccting tubule ond duct ‘Angiotensin IL Proximal tubule. tick ascending leop of Henleldistal ‘ubuk, collecting tubule Antidiuretie hormone Distal mbule/colleeting tubule and duct ‘Atrial natriuretic peptide Distal tubulo‘colecting tubule and éuct Parathyroid hormone Proximal tubule, thick ascending loop of ‘enleldistal tubule

صفحه 106:
Praia = 1 09۱ Amount filtered = Amount excreted GFR X Prin = Ulin XV ۷ نا ‎GFR = in XY‏ 3 6۳8 - 125 ۷ Unuiin < 125 ۳9۷۷ ۷۰۱ ‏ملام‎ ‎© Elsevier. Guyton & Hall: Textbook of Medical Physiology 11e - www.studentconsult.com

صفحه 107:
Sorum creatinine concentration (mg/dl) Creatinine production and Tena excretion (g/day) © Elsevier, Guyton & Hall: Textbook of Madical Physiology 116 - www.studentconsult.com

صفحه 108:
او 5.86 > بيرجلا ۱ ۶ ۷ ‎Elsevier. Guyton & Hall: Textbook of Medical Physiology 11e - www.studentconsult.com‏ ©

صفحه 109:
& > 5 8 4 8 5 1 a 60 GFR (mL/min) {© Else, Cao: Esoi'sIntzaratad Physiology - wr. sadentconsult com

صفحه 110:
سا ماه None salina مه min ‎oF min‏ ام ولج ‎nl, evclinin, mg in‏ ‏موه مه رصم شاوی ‎Gna SY ‎ ‏۷ سول ‎Tha ‏اتسار ‎Use of Clearance to Quantity Kidney Function ‏سس ‏دنا ‏0 ‎ ‎ ‎(Clearance rato ‏سمت دمع ‎ ‎Con ‎“Enany” (Pn Vesna ‎ ‎Pon ‎REF ‎ ‎Ror. ‎T-Hematoe ‎Excretion ate = Uc Reabnorption rate Pllered loa - Excretion rate ‎[ares t)=,2¥) Excretion ate Flee los ‎ ‎Secretion rte ‎tem ‏مه سس‎ ‎{Gomera ration rato (GER) ‏سس‎ ratio ‎renal plasm fw (ERPF)‏ ملسا ‎‘Rona plasma flow (RPP) ‎Rona blood ow (RIF) ‎rate‏ ماما ‎Reabsoepion rte‏ ‎suri me corer: Howe pam ‏امو‎ PAE, are ‏لفق لوج مجاه‎ oa aera PA ene Eg PA ‏تساه‎ six Voy ‏الا یه‎ cmc ‎ ‎

صفحه 111:
® Urine concentration

صفحه 112:
Ow 600 mOsm/day be 7200 mi 1 0.5 L/day — Usa * V Com ۳ osm

صفحه 113:
Ow =V—Com = V — Un XV) Cio =V Com = VE Pysn = 2.1 x Plasma sodium concentration

صفحه 114:
NaCl H,0 7 حچست 6000 i 1 © Elsevier. Guyton & Hall: Textbook of Medical Physiology 11e - www.studentconsult.com

صفحه 115:
fia {€) Countercurrent exchange in the vasa recta ‏يميه سا سس لت سيب سا سسا اناري‎ of ions in his region creates ‘Acne reabecrption| 2

صفحه 116:
(© Hever Guylon& Hal Textbook of Medical Physloloay Le - ww studenkeonsulteom

صفحه 117:
/ -> ورد ایو ‎medula a‏ ١ ۱ 1 i ' 1 ! © Elsevier. Guyton & Hall: Textbook of Medical Physioloay 11e - www.studentconsult.com

صفحه 118:
Inner medulla FIGURE 38-17 Operation of the vasa recta as ‘countercurrent exchangers in the kidney. NaCl and urea diffuse out of the ascending limb of the vessel and into the descending limb, whereas water difluses out of the descending and into the ascending limb of the vascular loop.

صفحه 119:
۱ ‘Vasopressin makes the eotecting act permeable to water. {ayer manima esopresi, he cotecing ducts reay permeable (eo te absence ‏چا وی ما وهی اه‎ 10 water War leaves Dy osmosis and scarred ay by he vasa Ipereanito water ana ie umes ute ‘cla captarss, Una conoonraou oe | امه مود موه Vasa recta 900 mom 530530

صفحه 120:
Cross sation at ‏وی‎ duct

صفحه 121:
Glomerulus capsule Proximal 1) Filrate isotonic to plasma tubule: a @ Proximal woe eabeorton 900 wy» @Pe0 veabsorved: NaC! and vba. 1000 Interstitial diffuse in ) SF) fluid osmolarity 300 mOsm —(@) Tight unctions water 400, impermeable — NaCl acthely ‏منم‎ 400 0۵0 160 ی ‘impermeable — NaCl actey reabsorbed مه مق مه ام ‎ie ADH. ro‏ @ aon ator eavsnood ithe ADH. no wntereaborbed Oe Vino ACH, no air eaboatod © Else Cao: Esoa'sIntearatad Physlloay - won. sudentconsuitcom

صفحه 122:
‎osmotarty‏ ماه رز ‎J ADH secretion (posterior pituitary) ‎| ‎J Pasme ADH ‎| ‎HO permeatilty in distal tubules, collecting ducts ‎| ‎‘41,0 reabsorption ‎| ‎{ieee ‎© Elsevier. Guyton & Hall: Textbook of Medical Physioloay 11e - www.studentconsult.com

صفحه 123:
Summary of Tubule Characteristics—Urine Concentration ‘Active Nac Permeabiity 1۳200000. 1۵ 1۵۵ Urea Proximal tubule + ‏مد‎ + Thin descending limb 0 ‏بو‎ ‎‘Thin ascending limb 0 o + + Thick ascending limb 4 ‏إلى‎ 8 0 Distal tubule ADH 0 Cortical collecting + 4ADH 0 3 ‘bul Inner medullary + ‏الاصهد‎ 00 ADEE collecting duct inna lve active tamper permeability; moderate level active ‏وا ماه مج مه‎ feel of ‏سره سدع‎ ADH, permeability to walcr or urea inceased by ADH

صفحه 124:
1250 Osmolarity (mOsmiL)

صفحه 125:

صفحه 126:
1 sine مه «معنالاة میدوب و شهب سیر مه بسرت اوم ©

صفحه 127:
۳ © Isovolemic osmoiic increase Pyyp = 1.3 6-017 0 we = 13 40 35 30 25 20 18 10 5 0 171000 ‏هه وه وه‎ Per cent change © Elsevier. Guyton & Hall: Textbook of Medical Physioloay 11e - www.studentconsult.com Plasma ADH (pg/ml)

صفحه 128:
Regulation of ADH Secretion J Plasma osmolarity T Blood volume T Blood pressure Drugs: Alcohol Clonidine (antihypertensive drug) Haloperidol (dopamine blocker) Increase ADH T Plasma osmolarity 4 Blood volume 4 Blood pressure Nausea Hypoxia Drugs: Morphine Nicotine Cyclophosphamide

صفحه 129:

صفحه 130:
152 148 144 140 Plasma sodium concentration (mEq/L) 136 0 30 60 90 120 150 180 ‘Sodium intake (mEqj/day) © Elsevier. Guyton & Hall: Textbook of Medical Physioloay 11e - www.studentconsult.com

صفحه 131:
Decrease Thirst { Osmolarity T Blood volume T Blood pressure 4 Angiotensin II Gastric distention Control of Thirst Increase Thirst T Osmolarity + Blood volume { Blood pressure Angiotensin Dryness of mouth

صفحه 132:
© 30 60 90 120 150 180 210 ‘Sodium intake (mEq/L) © Elsevier. Guyton & Hall: Textbook of Medical Physiology 11e - www.studentconsult.com

صفحه 133:
H,0 filtered load = 125 mL/min © Else, Cao: Esoar'sIntearatad Physiology - won sudentconsuitcom

صفحه 134:
۱ Thin descending Thin ascending Loop of Henle {Else Cao: Eso'sIntearatad Physiology - wom. sudantconsultcom

صفحه 135:
Collecting duct K+ filtered load = 0.5 mEq/min Medullary Thin descending Loop of Henle © Else, Cao: Esov'sIntarated Physlloay - wom sudantconsutcom

صفحه 136:
Urea filtered ۱0۵0 - 6 ۵۸ Collecting Thin descending Thin ascending

صفحه 137:
اسلام بر خلاف مذاهب دیگری که توجیه کننده ی فقر را مناسبات زندگی اجتماعی میدانند. بزرگترین آموزش یافته ی مکتبش ابوذر میگوید: "وقتی فقر وارد خانه ای میشود. دین از درب دیگر خارج میشود" و یا پیامبر اسلام حضرت محمد (ص) که بنیانگذار مکتبی است که همه ما مسلمانان به آن اعتقاد راسخ داریم چه شیوا و ساده بیان فرموده است: "من لا معاش له لا معاد له" کسی که زندگی مادی ندارد زندگی معنوی ‎aaa‏ ‏چون؛ شکم خالی هیچ ندارد. جامعه ای که دچار کمبود اقتصادی و مادی است مسلماً کمبود های معنوی بسیاری خواهد داشت و آنچه را که در جامعه های فقیر آنرا اخلاق و مذهب می نامند» متاسفانه معنویت در آن جایی ندارد.

صفحه 138:
© میخواهم بگویم؛ فقر همه جا سر میکشد ... © فقرء گرسنگی نیست. عریانی هم نیست ...فقر محتی گاهی زیر شمش های طلا خود را پنهان میکند... © فقر. چیزی را "نداشتن" است ؛ ولی آن چیز پول نیست ؛ طلا و غذا هم نیست . © فقر. ذهن هارا مبتلا ميكند ... © فقر ء اعجوبه ايست كه بشكه هاى نفت در عربستان را تا ته سر ميكشد * فقر» همان گرد و خاکی است که بر کتابهای فروش نرفته ی یک کتابقروشی می نشیند ... © فقرء تیه های برنده ماشین بازیافت است که روزنامه های برگشتی را خرد میکند . * فقرء کتیبه‌ی سه هزر ساله ای است که روی آن یلدگاری نوشته اند .- © فقر. يوست موزی است که از پنجره یک اتومبیل به خیابان انداخته میشود ... فقر . همه جا سر میکشد ... © فقر. شب را "بی غذا" سر کردن نیست .. فقر :روز را "بی اندیشه" سر کردن است ...

صفحه 139:
Kt intake 100 mEq/day> Extracellular Intracellular fluid K* fluid K* 4.2mEqL 140 mEq/L x14 x28L 59m Eq 3920 mEq K+ output gz Urine 92 mEqiday Feces 8 mEqiday mEq/day Figure 29-41 Normal potassium intake, distribution of potassium in the body fiuids, and potassium output from the body.

صفحه 140:
# تنظیم غلظت پتاسیم. کلسیم و....مایع خارج سلولی © -غلظت طبيعى يتاسيم يلاسما برابر با ۴/۲ میلی ایکی والان در ليتر © -افزايش يتاسيم يلاسما منجر به ايست قلبى مى گردد © توزيع يتاسيم در بخش هاى مختلف به ترتيب ذيل است 108-9896 © ECF=2%® * بنابراین سلول ها می توانند در ایجاد تعادل پتاسیم یعنی هوموستاز آن نقش مهمی داشته باه © An overflow site for excess ECF potassium during hyperkalemia © A resource of potassium during hypokalemia © Therefore, redistribution of k+ between the intra- and extra- cellular compartments provides a first line of defense against changes in ECF potassium concentration

صفحه 141:
فاکتورهای افزایش دهنده جذب سلولی پتاسیم #انسولین ۰ آلدوسترون. تحریک بتا آدرنریک و آلکالوز فاکتورهای کاهش دهنده جذب سلولی پتاسیم # ديابت» آدیسون, بلوک بتا آدرنرژیک ۰ تخریب سلولی (سلول خونی و عضلانی) ۰ ورزش سنگین و افزایش یافتن اسمولاریته خارج سلولی #س: در صورت عدم وجود مکانیزم های تنظیمی دریافت مقدار ۱۰۰ ملی ایکی والان پتاسیم چه تاثیری بر پتاسیم پلاسما و عملکرد بدن داشت؟

صفحه 142:
‘and blood pressur ing aldosterone Secretion, underscoring the integrated functions of the Fenal and cardiovascular systems. ANG I increases. bload pressure both directly and indirectly through four ‘ational pathways (Fig, 20-10) 11 ANG i! increases vasopressin secretion. ANG I receptors in the hypothalamus initiate this reflex. Fluid retention in the kidney under the influence of vasopressin helps blood volume, thereby maintaining blond pressure 2 ANG I! stimulates thirst. Fluid ingestion is a behavioral response that expands blood volume and raises blood pressure, 3 ANG ilis one of the mast potent vasoconstrctors inown in humans, Vasoconstriction causes blood pressure to without a change in blood volume. 4 Activation of ANG It receptors inthe cardiovascular ccontrot © center increases sympathetic output tothe heart and Blood "© vessels. Sympathetic stimulation increases cardiac output ‘© and vasoconstriction, both of which increase blood © pressure, © 5.ANG I! increases proximal tubule Nareabsorption. ANGI ‘© stimulates an apical transporter, the Na-Hexchanger "© (WHE). Sodium reabsorption inthe proximal tubule is followed © by water reabsorption, so the net effe

صفحه 143:

صفحه 144:
ااا لس ‎|Table 20-1‏ Factors That Can Alter Potassium Distribution Between the Intra- and Extracellular Fluid Factors That Shift K° into Cells Factors That Shift K* Out of Cells (Decrease Extracellular [K"]) (Increase Extracellular (K*]) * Insulin * Insulin deficiency (diabetes « mellitus) * B-adrenergic stimulation * Aldosterone deficiency * Alkalosis (Addison’s disease) * B-adrenergic blockade * Acidosis © Cell lysis * Strenuous exercise * Increased extracellular fluid osmolarity

صفحه 145:
#اختلالات اسید و باز: #اسیدوز متابولیک منجر به هیپرکالمی آلکالوز متابولیک منجر به هیپوکالمی #علل احتمالی هیپرکالمی در اسیدو پمپ سدیم-پتاسیم اثیر منفی یون هیدروژن تجمع يافته بر فعالیت ® Acute acidosis: a decrease in potassium secretion due to Na/K pump inhibition ® Chronic acidosis: an increase in potassium secretion due to inhibition of reabsorption of water and sodium in proximal tubule lead to increase delivery them to distal portions of nephron which should reabsorb in these segments and also an increase in GFR.

صفحه 146:
= SSS ۳ ‏مرور‎ © هر چه مقدار فیلتراسیون گلومرولی بیشتر باشد میزان دفع؟ میزان بازجذب پتاسیم در لوله نزدیک ۶۵ درصد و بخش ضخیم هنله ۲۷ درصد # ترشح پناسیم که سلول های اصلی متخصص این امر بوده و در حالت طبیعی روزانه ۳۱ میلی اکی والان برابر ۴ درصد از پتاسیم را ترشح می کنند. ® در صورتی که روزانه مقدار دریافت پتاسیم ۱۰۰ میلی اکیوالان باشد کلیه ها باید حدود ‎AY‏ درصد آن را دفع کنند و از این مقدار ۳۱ درصد در بخش های انتهایی نفرون جمع آوری می گردد. -حدود ۸ میلی اکیوالان از طریق مدفوع دفع می گردد. © کته ‎٩۰‏ درصد سلول های توبول دور و مجاری جمع کننده سلول اصلی هستند. © ترشح پتاسیم بوسیله سلول های اصلی یک فرآیند دو مرحله است © ١-ورود‏ يتاسيم به سلول از طیق غشا قاعده ای بوسیله پمپ سدیم-چتاسیم -خروج پتاسیم از سلول های فوق از طریق غشا لومینال

صفحه 147:
Luminal membranes of principal cells are highly permeable to potassium. They have epithelial potassium channels in this membrane. e © Intercalated cells can reabsorb potassium during potassium depletion. © It maybe occurs through K-H ATPase located in the luminal membrane. ۰ © Key factors stimulate potassium secretion by principal cells © [K*] ‏بو‎ 2. Aldosterone increment and 3. High flow rate of tubular fluid ۰ © The most potent releaser of aldosterone is hyperkalemia. © If potassium concentration increases from 3.5 to 6, plasma aldosterone levels increase up to 10 times.

صفحه 148:
Control of renal calcium excretion and calcium ECF concentration ©[Ca].cp=2.4 meq/L °©50% as ionized or free form ©40%= bound to plasma proteins ©10%=complex with phosphate and citrate. © Hypocalcemia leads to neuronal hyper-excitability (Tetany) ۰ © Hypercalcemia leads to decrease neuronal excitability (Coma) © Unlike other ions such as sodium, potassium and ..., a large share of calcium excretion occurs in the feces. ۰

صفحه 149:
Pin © Day to day regulation of calcium concentration is mediated in large part by the effect of PTH on bone resorption © This hormone © 1. Stimulate bone resorption © 2. Activate vitamin D and © 3. directly increases renal tubular calcium reabsorption

صفحه 150:
چون کلسیم ترشح نمی گردد بنابراین میزان دفع آن از فرمول ذیل محاسبه می گردد ‎Renal calcium excretion=Ca filtered-Ca‏ © ‎reabsorbed‏ ‎٩‏ درصد کلسیم به ترتیب در لوله نزدیک (۶۵» ضخیم هنله (۲۵-۳۰)و لوله دور و جمع كتنده (20-5) بازتجذب.مى كردق ‏عوامل افزايش دهنده بازجذب كلسيم ‎PTH, Hypocalcemia, hypotention,‏ ‎hyperphostamemia, metabolic acidosis, VitD‏ #عوامل کاهش دهنده بازجذب کلسیم عکس موارد فوق در زمان هیپرتانسیون ی افزایش حجم مایع خارج سلولى به دليل بالا بودن 61718 و افزایش سرعت مایع توبولی بازجذب؟؟؟؟

صفحه 151:
ار © توبول هاى كليوى براى بازجذب نشان می دهند. هر گاه خی پلاسمایی از :1۸ - میلی مولار بیقتر شود در امرار ظاهر می گرده: ‎CC (Plasma) 0.8mM‏ 1000© ‎©125CC(GFR) 0.1mM‏ این ترکیب کاینیتیک حداکثر اشباع (۰.۱ ن قشک لیدودر دفع ف سفاندارد #منيزيم محل بازجذب توبول نزدیک (۳۵) ضخيم هنله (۶۵) و لوله دور درصد # در شرایط هیپرمنیزمی, هیپرکلسمی و افزایش ‎ECF exe‏ میزان دفع منیزیم افزايش مى يابد.

صفحه 152:
#مکانیزم های کلیوی کنترل حجم مایع خارج سلولی 8 حجم مایع خارج سلولی به وسیله تعادل بین دریافت آب و نمک تعیین می گردد. #دفع سدیم به وسیله دو متغیر 23718-۱) و ۲- میزان بازجذب کنترل می گردد. ® Sodium excretion= GFR-Reabsorption. ‏درصورتی که اختلالی هریک از دو متفیر فوق را تحت تاثیر قرار دهد‎ ‏مکانیزم های بافری وارد عمل می گردد‎ ® Glomerulotubular balance ® Macula densa feedback

صفحه 153:
C— +—_ ‏ک‎ @ FIGURE QUESTION Map the cardiovascular reflex patnway represented by me@.

صفحه 154:
اهمیت دیورز و ناتریورز فشاری در تنظیم تعادل آب و سدیم © تعريف ديورز؟ #به اثر فشار خون بر دفع سديم ناتريورز فشارى و بر دفع آب ديورز فشاری كويند. #دو يديده فوق مكانيزم هاى فيدبكى كليدى بدن براى تنظيم مايعات بدن و فشار شريانى مى باشند افزایش دریافت آب و نمک: افزایش حجم مایع 2617 : افزایش حجم خون: افزایش میانگین فشار پرشدگی عروقی: افزایش با زگشت وریدی: افزایش برون ده قلبی: افزایش فشار خون: افزايش *۵1) : دیورز فشاری # بنابراين تغییرات بزرگ در دریافت مایع و نمک در شرایط فیزیولوژیک تاثیر کمی بر حجم خون . فشار خون و حجم ‎sable wales ECF‏

صفحه 155:
bution of ECF be and plasma #در صورتى كه مقدار كمى مايع به دليل نوشيدن زياد يا کاهش برون ده کلیوی در خون تجمع یابد حدود ۲۰-۳۰ درصد آن پس از مدتی به 19۳ وارد شده مابقی در سیستم عروقی باقی خواهد ماند ولی اگر میزان تجمع مایع زیاد باشد ۵۰ درصد از آن به 15 وارد می شود که این مساله باعث ایجاد ادم می گردد ولی از طرفی ورود این بار اضافی به فضاى ميان بافتی در شرایط تحت ‎Overload 3) o&‏ قلب می کاهد (نقش کاردیوپروتکتیو).

صفحه 156:
‘and hormonal mechanism: with the pressure natriuresis and pressure diuresis, making them more effective in minimizing the changes in blood volume, ECF volume and arterial pressure that occur in response to day-to-day challenges. کنترل دفع کلیوی: رفلکس گیرنده بارورسپتو شریانی و گیرنده حجمی ‎Hemorrhage: a decrease in pressure of pulmonary blood‏ ‎vessel: activation of sympathetic system leads to‏ ‎Vasoconstricing the afferent arteriole‏ 1 ‎2decrease GFR‏ ‎Activation of RAS‏ 3 ‎4And ultimately increase tubular reabsorption (water and‏ ‎salt)‏

صفحه 157:
افزایش تكلا"نا باتولوزيى ۸00102 تاثیر قابل ملاح ظ ندارد زیر افزایش آنژیو۲: احتباس آب و سدیم توسط کلیه ها: افزايش حجم 3۳ : افزایش 13 : دیورز و ناتریورز فشاری: تصحیح حجم خارج سلولی. آلدوسترون نیز با بازجذب سدیم منجر به احتباس آب و سدیم و دفع پتاسیم می گردد. فرار آلدوسترونی: # در صورت انفیوژن آلدوسترون یا تومور غده فوق کلیه (سندرم كن ) افزايش بازجذ توبولی سدیم و کاهش دفع ادراری آن گذرا خواهد بود. زیر: یک تا سه روز پس از احتباس آب و سدیم: افزایش حجم "3.623 به میزان ۱۰-۱۵ درصد: افزايش هم زمان 13۳ : دیورز فشاری (در اين زمان کلیه ها از احتباس آب و نمک فرار کرده و از آن پس مقادیر ورودی با خروجی برابر خواهد بود) * فقدان آلدوسترون یا کاهش يافتن ترشح آن: افت شدید حجم ۳6/۳ ‎The most important role of aldosterone is to‏ © ‎maintain the volume of ECF‏

صفحه 158:
ترشح ‎ADH‏ تاثير اندکی بر حجم ‎BP , ECF‏ دارد. افزايش ](۸1 نیز تاثیر اندکی بر بر حجم 30/۳ و 3 دارد که به دلیل ایجاد دیورز فشاری می باشد. #ولى افزايش 21011 می تواند منجر به هیپوناترمی گردد (هم رقیق شدن سطح پلاسمایی سدیم به دلیل افزایش بازجذب آب و هم ایجاد دیورز فشاری)

صفحه 159:
FIGURE 40-1 Secretion of acid by proximal tubular cells in the kidney. H* is transported into the tubular lumen by an antiport in exchange for Na*. Active transport by Na, K ATPase is indicated by ar- rows in the circle. Dashed arrows indicate diffusion.

صفحه 160:
Regulation of Acid-Base Balance

صفحه 161:
FIGURE 40-2 Feat crates audi ange {orl Top fabio iteedeiatortn CO, Mae: ‏ای ره 0غ‎ ۱ ‏ا‎

صفحه 162:
خب + ولا هس ربا Catarina SUS ‏مدای‎ NH? Glutamic ‏واوتهاناوماهكاه امعط نامدا مسسنتخ‎ + ۱ FIGURE 40-3 Major reactions involved in ammonia production in the kidneys.

صفحه 163:
FIGURE 29-5 summary ‏دوع و فصو اوه 99اه‎ ۱۵ mutate of akostroesertion by angetanshl Ths ps maronsreatonctenn itera Ineingsaphirereio-ar yore yan; tease ‏ده إن م‎ ngee a ٠ ‏تخاس‎

صفحه 164:
Definitions : Acids : Molecules can release hydrogen ions in solutions (HCl & H2CO3) Bases : A base is an ion or a molecule that can accept an H+. For example, HCO3 & HPO4 The proteins in the body also function as bases, because some of the amino acids that make up proteins have net negative charges that readily accept H+. The protein hemoglobin in the RBCs and proteins in the other cells of the body are among the most important of the body’s bases.

صفحه 165:
1فرار : اسیدهائی که ‎Wo‏ توانند توسط ریه ها دفع شوند (4112003 2) غیرفرار : به طور عمده توسط متابولیسم پروتئین ها تولید می شوند و نمی توانند توسط ریه ها دفع شوند بدن روزانه حدود 80 10۳76 اسید غیرفرار تولید می کند (از متابولیسم پروتئین ها که فقط توسط کلیه ها باید دفع دد

صفحه 166:
synonymously An alkali is a molecule formed by the combination of one or more of the alkaline metals—sodium, potassium, lithium, and so forth—with a highly basic ion such as a hydroxyl ion (OH-). The base portion of these molecules reacts quickly with H+ to remove it from solution; they are, therefore, typical bases. For similar reasons, the term alkalosis refers to excess removal of H+ from the body fluids, in contrast to the excess addition of H+, which is referred to as acidosis. Alkalosis pH>7.4, Acidosis pH<7.4

صفحه 167:
rong and A strong acid is one that rapidly dissociates and releases especially large amounts of H+ in solution (HCl). Weak acids ............ H2CO3 A strong base is one that reacts rapidly and strongly with H+ and, therefore, quickly removes these from a solution (example is OH-, which reacts with H+ to form water (H20) A typical weak base is HCO3 because it binds with H+ much more weakly than does OH- Most of the acids and bases in the ECF that are involved in normal acid-base regulation are weak acids and bases

صفحه 168:
Buffer systems do not eliminate H+ from or add them to the body but only keep them tied up until balance can be reestablished. 1. Chemical B. : a few seconds 2. Respiratory B. system : a few minutes (acts within a few minutes to eliminate CO2 and, therefore, H2CO3 from the body). 3. Kidneys B. (a few hours to days) : can eliminate the excess acid or base from the body, the strongest system. H ions origin : In the body : 0.00004 mEq/L (40 nEq/L). Produced during or ingested : 80 mEq/day (Without buffering, the daily production and ingestion of acids would cause huge changes in body fluid H+ concentration)

صفحه 169:
pH and H* Concentration of Body Fluids pH 7.40 7.35 7.35 6.0 to 7.4 45 to 8.0 08 Ht Concentration (mEq/L) 40x10 45x 10" 45x10" 1x 10 to 4x 10° 3x 107 to 1x 10% 160 Extracellular fluid Arterial blood Venous blood Interstitial fluid Intracellular fluid Urine Gastric HCl

صفحه 170:
1 ۳ For example, the normal ]111[ is 40nEq/L (0.00000004 Eq/L). Therefore, the normal pH is pH =-log [0.00000004] pH=7.4 =-log[H"] pH =log

صفحه 171:
Buffering of Hydrogen Ions in the Body Fluids A buffer is any substance that can reversibly bind H+. The general form of the buffering reaction is Buffer +H* <——~ H Buffer

صفحه 172:
(Puvtors thot detercoicates the ubiliy oP buPPer systesw Cd.0CQ spstew سدس امج دومج لو ‎S.QuPPer‏ اه بر موی جر خأن جصتدانيج 8), 9 اد

صفحه 173:
Bicarb The bicarbonate buffer system consists of a water solution that contains two ingredients: (1) a weak acid, H2CO3, and (2) a bicarbonate salt, such as NaHCO3. H2CO3 is formed in the body by the reaction of CO2 with H20. 0 002 + H20*— 3 H2CO3 ۲1+ + 37 Carbonic anhydrase is especially abundant in the walls of the lung alveoli, where CO2 is released & also present in the epithelial cells of the renal tubules, where CO2 reacts with H20 to form H2CO3.

صفحه 174:
HCO; ~~ ۲۲۳ +۲ ۷ص :1:۱0 سح 60:11:0 لاك ۹ Nat

صفحه 175:
bicarbonate buffer solution, the increased H+ released from the acid (HCl H + Cl) is buffered by HCO3 ‎O¢vLCOD => Oui + 09‏ + الراك ‎As a result, more H2CO3 is formed, causing increased CO2 and H20 production

صفحه 176:
with H2CO3 to foun additional HCO3. Thus, the weak base NaHCO3 replaces the strong base NaOH. At the same time, the concentration of H2CO3 decreases (because reacts with NaOH), causing more CO2 to combine with H20 to replace the H2CO3 NaOH + H,CO; —> NaHCO, + HO The net result, therefore, is a tendency for the CO2 levels in the blood to decrease, but the decreased CO2 in the blood inhibits respiration and decreases the rateof CO2 expiration.The rise in blood HCO3 that occurs is compensated for by increased renal excretion of HCO3

صفحه 177:
100 75 ‘added ‏احج‎ Heo, Per cant of buffer in form of 50 25 وت pK H,CO, and CO, ‏ام‎ سس ‎Acid adie‏ هس ‎er cent of buffer i form of‏ 8 Figure 30-4 Tiration curve for bicarbonate butfer system showing the pH of extraceluer fLid when the percentages of fufler in the form of HCO, “and CO, (or H.C.) are ‏اه‎

صفحه 178:
Bicarbonate Buffer System 1. PK=6.1 2. Concentration of ingredients regulates by kidneys and respiratory system Thus, Bicarbonate Buffer System is the most important and strongest system in ECF

صفحه 179:
“Phosphate Buffer System —— 1. The phosphate buffer system is not important as an ECF buffer 2. It plays a major role in buffering renal tubular fluid and ICF 3. The main elements of the phosphate buffer system are H2PO4 and HPO4 ۳۱۳۵ ۳۱۳0۵

صفحه 180:
“When a strong ‏سس سس‎ 5 mixture of these two substances, the hydrogen is accepted by the base HPO4 and converted to H2P04 HCl + Na;sHPO, —> NaH>PO, + NaCl When a strong base, such as NaOH, is added to the buffer system, the OH is buffered by the H2PO4to form additional amounts of HPO4 + H’ NaOH + NaH.PO, —> NaHPO, + HO

صفحه 181:
1. pK = 6.8 which is not far from the normal pH = 7.4 in the body fluids 2. Its concentration in the ECF is low (about 8 % of the concentration of the bicarbonate buffer) In contrast to its rather insignificant role as an extracellular buffer , the phosphate buffer is especially important in the tubular fluids of the kidneys and intracellular fluid 1. It usually becomes greatly concentrated in the tubules 2. the tubular fluid usually has a considerably lower pH than the ECF does, bringing the operating range of the buffer closer to the pK (6.8) of the system 3.The concentration of phosphate in this fluid (ICF) is many times that in the ECF 4.. Also, the pH of intracellular fluid is < that of ECF and therefore is usually closer to the pK of the phosphate buffer system compared with the ECF.

صفحه 182:
roteins: I 5 Buffers Proteins are among the most plentiful buffers in the body because of their high concentrations, especially within the cells. The pH of the cells, although slightly < in the ECF, nevertheless changes approximately in proportion to ECF pH changes. There is a slight amount of diffusion of H+ and HCO3 through the cell membrane, although these ions require several hours to come to equilibrium with the extracellular fluid, except for rapid equilibrium that occurs in the red blood cells. C02, however, can rapidly diffuse through all the cell membranes. This diffusion of the elements of the bicarbonate buffer system causes the pH in intracellular fluid to change when there are changes in extracellular pH. For this reason, the buffer systems within the cells help prevent changes in the pH of ECF but may take several hours to become maximally effective.

صفحه 183:
buffer, as follows: H* + Hb —— HHb Approximately 60 to 70 % of the total chemical buffering of the body fluids is inside the cells, and most of this results from the intracellular proteins. In addition to the high concentration of proteins in the cells, another factor that contributes to their buffering power is the fact that the pKs of many of these protein systems are fairly close to 7.4.

صفحه 184:
tory Re The second line of defense against acid-base disturbances is control of ECF CO2 concentration by the lungs. t Ventilarom—>f co, 2۳۳۳ [E+] ‏مین‎ ‏كت حت‎ Ventilation CO, Elimination مین ۱۳1۹1

صفحه 185:
Agents that determine the concentration of CO2 1. metabolic formation rate 2. pulmonary ventilation. Increasing alveolar ventilation to about twice normal raises the pH of the ECF by about 0.23 (PH 7.4 7.63) ‏محر‎ reducing the ventilation to one fourth normal reduces the pH to 6.95.

صفحه 186:
25 05 10 15 20 Rate of alveolar ventilation (normal = 1) 668 52 Lit in body fluids ° 1 0.13 ع ‎O24‏ pH change bb S28

صفحه 187:
70 71 Alveolar ventilation (normal 72,73 74 75 76 pH of arterial blood Ena Effect of blood pH on the rete of alveolar ventilation,

صفحه 188:
اس 5 _ و6 كص ج02) م19 مسل را ۶و اون T{H*] > TAlveolar ventilation کارآنی کننرل تنقسن غلظت بون هبدروژن : کنترل تنفسی کاملا قادر به برگرداندن ۲ به میزان طبیعی نیست یعنی اینکه موثر بودن این سیستم به میزان 50 تا 75 درصد است. به عنوان مثال قادر است 2 با" را به میزان 0/2 تا 0/3 ارتقاء دهد یعنی رج رصح

صفحه 189:
بافرهای شیمیائی بدن ‎Buffer potency comparison‏ ‎respiratory system >> chemical‏ system قدرت بافری سیستم تنفسی یک تا دو برابر بیشتر از قدرت بافری تمام بافرهای دیگر موجود در "120۳ است

صفحه 190:
کلیه ها با تغيير دادن 253 ادرار, 213 مایعات خارج سلولی را تنظیم می کنند در شرایط اسیدوز دفع ادرار اسیدی : بازجذب بیشتر ۲1003 و ترشح بیشتر یون ۲1 در شرایط آلکالوز دفع ادرار بازی : بازجذب کمتر ۲1003 و کاهش ترشح پون 1

صفحه 191:
1)ترشح یون های هیدروژن 2 با زجذب یون های بیکربنات فیلتره شده 3)تولید یون های بیکربنات جدید

صفحه 192:
78 0 Rosbeoration of bicarbonate in differ feni segmenis of te tenal tubule, The percentages of the tered losd of Bicarbonate absorbed by the various lubuiar segments ste shown, as wel faethe numbsr of millecuvalente Feebsoibed per day under nommal condivons, 85% (2672 mEqiéay) 4320 mEqiday 10% (492 mE lay) وود رت رلا وعد م

صفحه 193:
onal Tubular oral “Tubular cells timer fat Na+ HCO, هيا + يمع Calla mechanisms for (1) acne secretion hydrogen ins ito the renal ube ©) buat ressasrpion cr Hicabenate fe by combination van hydrogen ns term carbons acid uth c fecintes erm cotbon douse snd wate and (3) sod um fon ‘eahcerion in exchange for hyciogen ions secreted. Th pater ‏دی مارا تسده مامت مط موش‎ tubule Wide ‏مرسمه‎ segment ofthe lop ol Henle, and the earl, dal iba

صفحه 194:
Rona! “Tubular ‏عم مهن از‎ ع Primary acive sectetion of fyctogen ions theuah the lumina ‘membrane ofthe hetcalted epthelaloele of te Ine dat and Soieeing ules Nets that ane Hleabona an ‏:د مسا ج‎ ‘ach halogen kn secreted and « chixide ion is. pecoively Secreted slong withthe hydrogen ion

صفحه 195:
O.LCOF ard WOPOFP bevowe cvareuirated io the tubular Puid bemouse oF their retaively poor ‏جومم سر‎ ©. ‏جما له اوه له‎ ure te ski acide, ood the utc pL t& crar he AK = 0.0 oP the phosphdte buPPer systew. wherever ‏بلا" جد‎ seoreted tity te tuber keoed oowbker wi ober voter tar LOO9, te wet PP Pent i addiica oP a eu/LOO9 te the bbod.

صفحه 196:
Renal Tubular interstitial Tubular cells lumen fluid Na*+NaHPO,- Nat “oO. H+ NaHPO,- ==-HCO,-+ Ht H,CO, NaH,PO, Carbonic anhydrase | ‏از‎ 3 co, Figure 30-7 Buffering of secreted hydrogen ions by filtered phosphate (NaHPO,). Note that a new bicarbonate ion is returned to the blood for each NaHPO,; that reacts with a secreted hydrogen ion

صفحه 197:
Under normal conditions, much of the filtered phosphate is reabsorbed, and only about 30 to 40 mEq/day is available for buffering H+. Therefore, much of the buffering of excess H+ in the tubular fluid in acidosis occurs through the ammonia buffer system.

صفحه 198:
۱0۵۳ 0۲ ۴۱6655 ۷۲00 Generation of New Bicarbonate by the Ammonia Buffer System A second buffer system in the tubular fluid that is even more important quantitatively than the phosphate buffer system is composed of ammonia (NH3) and the ammonium ion (NH4). Ammonium ion is synthesized from glutamine, which comes mainly from the metabolism of amino acids in the liver. The glutamine delivered to the kidneys is transported into the epithelial cells of the proximal tubules, thick ascending limb of the loop of Henle, and distal tubules (Figure 30-8). Once inside the cell, each molecule of glutamine is metabolized in a series of reactions to ultimately form two NH4 and two HCO3. The HCO3 generated by this process constitutes new bicarbonate.

صفحه 199:
Tubular = lumen Renal interstitial fluid Proximal tubular cells Glutamine ——————_ Guta ~€---2HCO,- 2NH,* | “ON cr Na+ Nat Figure 30-8 Production and secretion of ammonium ion (NH,*) by proximal tubular cells. Glutamine is metabolized in the cell, yielding NH,* and bicarbonate. The NH,° is secreted into the lumen by a sodium-NH,* pump. For each glutamine molecule metabolized, two NH." are produced and secreted and two HCO, are returned to the blood.

صفحه 200:
The addition of NH4 to the tubular fluids occurs through a different mechanism (Figure 30-9). Here, H is secreted by the tubular membrane into the lumen, where it combines with NH3 to form NH4, which is then excreted. The collecting ducts are permeable to NH3, which can easily diffuse into the tubular lumen. However, the luminal membrane of this part of the tubules is much less permeable to NH4; therefore, once the H has reacted with NH3 to form NH4, the NH4 is trapped in the tubular lumen and eliminated in the urine. For each NH4 excreted, a new HCO3 is generated and added to the blood.

صفحه 201:
Renal Tubular —_ ‎Collecting ۱‏ نس ‎a tubular cells lumen‏ ‎ ‎cr ‏دس‎ ۱60+ ۴ H,CO, Carbonic NH,*+ Cr anhydrase 0 0 ‎ ‎+ ‎co, ‎Figure 30-9 ‎Buffering of hydrogen ion secretion by ammonia (NH.) in the col- lecting tubules. Ammonia diffuses into the tubular lumen. where it reacts with secreted hydrogen ions to form NH,*, which is then excreted. For each NH,' excreted, a new HCO, is formed in the tubular cells and returned to the blood

صفحه 202:
One of the most important features of the renal ammonium-ammonia buffer system is that it is subject to physiologic control. t ۱۳۲۱ ‏عع‎ = t stimulates renal glutamine t ‏كك‎ formation of NH4 New HCO3 to be used in H buffering; A decrease in H+ concentration has the opposite effect.

صفحه 203:
لس وه طولب( ۳۲۶ ‏له موه عل روا مه بل خاب امجمه‎ systew uovouts Por bout SO per cect of the uid excreted und GO per cect oP the ce WOOO yeuersied by the ‏عولط‎ وله سا 0 و ‎Dhe rote oP OWE excretivg co reuse 7 os work‏ ‎wEqday. Therefore, wi chrooic uctdosis, the dowiccdt weckodisc by‏ whic acid is elevated is excretioa oP OWE. This usv provides the wost ispportiat weohodisw Por yeurrotiggy ‏سوه‎ ‎۱ dura chrouir uvidosis.

صفحه 204:
Factors That Increase or Decrease H* Secretion and HCO; Reabsorption by the Renal Tubules Increase H* Secretion and Decrease H* Secretion and HCO; Reabsorption HCO, Reabsorption T Pcoz 4 Pco; 11 HCO; LH’, T HCO: 4 Extracellular fluid volume T Extracellular fluid volume 7 Angiotensin II 4 Angiotensin I 7 Aldosterone 4 Aldosterone Hypokalemia Hyperkalemia

صفحه 205:
Characteristics of Primary Acid-Base Disturbances pH HY Pco, HCO,” Normal 7.4 40mEq/L 40mmHg 24 mEq/L. Respiratory acidosis 1 ٩ 11 1 Respiratory alkalosis T 1 dW L Metabolic acidosis L of 4 dw Metabolic alkalosis oT J 1 11 ‘The primary event is indicated by the double arrows (17 or 11). Note that respiratory acid-base disorders are initiated by an increase or decrease in PCO, whereas metabolic disorders are initiated by an increase or decrease in HCO.

صفحه 206:
كً ——— =a TA pH? I 274 aed i is mn Hg stat fat <40 mia wat ‏سس تست ۳ امد‎ con HCO, HCO, ‏الو 2 و0‎ oad a Hg 4 Analysis of simple acid-base disorders, If the compensatory responses are markedly different from those shown at the bottom of the figure, one should suspect a mixed acid-base disorder.

صفحه 207:
| © 79 50 0 انر ‎i Ha)‏ ی ‎eid-bae9 nomogran. showing ‘teal blood pl avail pl HOO" “and Poo. values. The Cantal open ciclo’ shove tho Spprocmate is for ‏ده تاد‎ Status In normal people. The Shae! ena in the nemaqea Show the epprouats mits ‎lasma [HCO] mE!) ‏با و‎ ۵ ۵ 9 ۶ ۵ ۵ ٩ 8 ‎ ‎Arterial ‎ ‎hone for the ‘norma, compensations: ‎respiratory bused by simple melnbalic and ‎falas Pl (mmHg) Foepratery dserdete For vate ‎areas,‏ نهاك ددن لكات ورا ‏شاه ‎suspect amie‏ رده ‎2 0 7 0 | ‘terial blood oH Cogan MG, Recter Fe dr Asie ‎gee Dsorders nthe Richey ro 3. Phiacepis. NB. Saunders, 1365)

صفحه 208:
Table ata Metabolle Acidosis Assoelaed with Normal or Iereased Plasma anion Gap Ineease fon Gap ‘Honma Anion Gap (tormoeoromia) ‏تسس‎ Diabetes malin: (Ketaedosis)Diarrhou ste aides Renal tabular acidosis (Chronic ena ite ‏ها مس رل لت‎ ‏رقم نوالسوهاه مریم‎ Adow's elsease Métharel posoning Etiylene shoe! pesoning

 Urine Formation by the Kidneys: Glomerular Filtration, Renal Blood Flow, and Their Control Dr. Mard The kidneys serve multiple functions, including the following:  Excretion of metabolic waste products and foreign chemicals  Regulation of water and electrolyte balances  Regulation of body fluid osmolality and electrolyte concentrations  Regulation of arterial pressure  Regulation of acid-base balance  Secretion, metabolism, and excretion of hormones  Gluconeogenesis Excretion of metabolic waste products and foreign chemicals : include urea (from the metabolism of amino acids)  creatinine (from muscle creatine), uric acid (from nucleic acids)  end products of hemoglobin breakdown (such as bilirubin) metabolites of various hormones  most toxins and other foreign substances such as pesticides, drugs, and food additives. Regulation of Water and Electrolyte Balances. For maintenance of homeostasis, excretion of water and electrolytes must precisely match intake. Intake = Output (excretion) Figure 26-1 Effect of increasing sodium intake 10-fold (from 30 to 300 mEq/day) on urinary sodium excretion and extracellular fluid volume. The shaded areas represent the net sodium retention or the net sodium loss, determined from the difference between sodium intake and sodium excretion.  Regulation of Arterial Pressure Long-term regulation of arterial pressure by excreting variable amounts of sodium and water. Short-term arterial pressure regulation by secreting vasoactive factors or substances, such as Renin angiotensin II  Regulation of Acid-Base Balance The kidneys contribute to acid-base regulation, along with the lungs and body fluid buffers, by excreting acids and by regulating the body fluid buffer stores. The kidneys are the only means of eliminating from the body certain types of acids, such as sulfuric acid and phosphoric acid, generated by the metabolism of proteins. Regulation of Erythrocyte Production Hypoxia production erythropoietin Erythropoietin CRF (hemodialysis) RBC Anaemia The kidneys produce the active form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), by hydroxylating this vitamin at the "number 1" position. Physiologic Anatomy of the Kidneys Location : posterior wall of the abdomen (retroperitoneal) Weight : 150 gr Hilum : entrance of renal pedicles and ureter Fibrous capsule : The kidney is surrounded by a tough, that protects its delicate inner structures. The kidney composed of : two major regions that can be visualized are the outer cortex and the inner region (medulla). Renal pyramids : The medulla is divided into multiple coneshaped masses of tissue called renal pyramids. The base of each pyramid originates at the border between the cortex and medulla and terminates in the papilla, which projects into the space of the renal pelvis. Renal pelvis : a funnel-shaped continuation of the upper end of the ureter. The outer border of the pelvis is divided into openended pouches called major calyces that extend downward and divide into minor calyces Minor calyces : collect urine from the tubules of each papilla. contractile elements : The walls of the calyces, pelvis, and ureter contain contractile elements that propel the urine toward the bladder Renal Blood Supply Blood flow: is normally about 22% of the C.O or 1100 ml/min. The renal artery enters the kidney through the hilum and then branches progressively to form : Afferent arterioles glomerular capillaries Efferent arteriole peritubular capillaries  The renal circulation is unique in that it has two capillary beds, the glomerular and peritubular capillaries, which are arranged (in series), which help regulate the hydrostatic pressure in both sets of capillaries.  High hydro-static pressure in the glomerular capillaries (60 mm Hg) causes rapid fluid filtration,  Whereas a much lower hydrostatic pressure in the peritubular capillaries (about 13 mm Hg) permits rapid fluid reabsorption.  By adjusting the resistance of the afferent and efferent arterioles, the kidneys can regulate the hydrostatic pressure in both the glomerular and the peritubular capillaries, thereby changing the rate of glomerular filtration, tubular reabsorption The Nephron Is the Functional Unit of the Kidney Each kidney (1 million nephrons) Each nephrons capable of forming urine. The kidney cannot regenerate new nephrons Therefore, with renal injury, disease, or normal aging, there is a gradual decrease in nephron number. After age 40, the number of functioning nephrons usually decreases about 10 per cent every 10 years. Each nephron contains : (1)The glomerulus (2)a long tubule in which the filtered fluid is converted into urine on its way to the pelvis of the kidney The glomerulus contains a network of branching and anastomosing glomerular capillaries that, compared with other capillaries, have high hydrostatic pressure (60 mm Hg). The glomerular capillaries are covered by epithelial cells, and the total glomerulus is encased in Bowman's glomerular capsule. Fluid capillaries filtered flows into from the Bowman's capsule and then into the proximal tubule Innervation of the Bladder Pain sensation in ureter  Reflex. The ureters are well supplied with pain nerve  fibers. When a ureter becomes blocked (e.g., by a ureteral stone), intense reflex constriction occurs, which is associated with severe pain. Also, the pain impulses cause a sympathetic reflex back to the kidney to constrict the renal arterioles, thereby decreasing urine output from the kidney. This effect is called the ureterorenal reflex and is important for preventing excessive flow of fluid into the pelvis of a kidney with a blocked ureter.  Innervation of the Bladder.  The principal nerve supply of the bladder-the pelvic nerves, which connect with the spinal cord through the sacral plexus, (S2 and S3)  The sensory fibers detect the degree of stretch in the bladder wall.  Stretch signals from the posterior urethra are especially strong and are mainly responsible for initiating the reflexes that cause bladder emptying.   The motor nerves transmitted in the pelvic nerves are parasympathetic fibers.   In addition to the pelvic nerves, two other types of innervation are important in bladder function. Most important are the skeletal motor fibers transmitted through the pudendal nerve to the external bladder sphincter.  These fibers are somatic nerve fibers that innervate and control the voluntary skeletal muscle of the sphincter.   Also, the bladder receives sympathetic innervation from the sympathetic chain through the hypogastric nerves, connecting mainly with the L2 segment of the spinal cord. These sympathetic fibers stimulate mainly the blood vessels and have little to do with bladder contraction.  Some sensory nerve fibers also pass by way of the sympathetic nerves and may be important in the sensation of fullness and, in some instances, pain.  Figure 26-8 shows the approximate changes in intravesicular pressure as the bladder fills with urine. When there is no urine in the bladder, the intravesicular pressure is about 0, but by the time 30 to 50 milliliters of urine have collected, the pressure rises to 5 to 10 centimeters of water.  Additional urine—200 to 300 milliliters—can collect with only a small additional rise in pressure; this constant level of pressure is caused by intrinsic tone of the bladder wall. Beyond 300 to 400 milliliters, collection of more urine in the bladder causes the pressure to rise rapidly.  Superimposed on the tonic pressure changes during filling of the bladder are periodic acute increases in pressure that last from a few seconds to more than a minute. The pressure peaks may rise only a few centimeters of water or may rise to more than 100 centimeters of water. These pressure peaks are called micturition waves in the cystometrogram and are caused by the micturition reflex.  MICTURITION REFLEX  As the bladder fills, many superimposed micturition contractions begin to appear, as shown by the dashed spikes. They are the result of a stretch reflex initiated by sensory stretch receptors in the bladder wall, especially by the receptors in the posterior urethra when this area begins to fill with urine at the higher bladder pressures.   Sensory signals from the bladder stretch receptors are conducted to the sacral segments of the cord through the pelvic nerves and then reflexively back again to the bladder through the parasympathetic nerve fibers by way of these same nerves.  When the bladder is only partially filled, these micturition contractions usually relax spontaneously after a fraction  of a minute, the detrusor muscles stop contracting, and pressure falls back to the baseline.   As the bladder continues to fill, the micturition reflexes become more frequent and cause greater contractions of     the detrusor muscle. Once a micturition reflex begins, it is “self-regenerative.” That is, initial contraction of the bladder activates the stretch receptors to cause a greater increase in sensory impulses from the bladder and posterior urethra, which causes a further increase in reflex contraction of the bladder; thus, the cycle is repeated again and again until the bladder has reached a strong degree of contraction.   Once the micturition reflex becomes powerful enough, it causes another reflex, which passes through the pudendal  nerves to the external sphincter to inhibit it. If this inhibition is more potent in the brain than the voluntary  constrictor signals to the external sphincter, urination will occur. If not, urination will not occur until the bladder fills still further and the micturition reflex becomes more powerful. Macula densa : At the end of the thick ascending limb is a short segment, which is actually a plaque in its wall, known as the macula densa Distal tubule : Beyond the macula densa, fluid enters the distal tubule, which, like the proximal tubule, lies in the renal cortex. This is followed by the connecting tubule and the cortical collecting tubule, which lead to the cortical collecting duct.  The initial parts of 8 to 10 cortical collecting ducts join to form a single larger collecting duct that runs downward into the medulla and becomes the medullary collecting duct.  The collecting ducts merge to form progressively larger ducts that eventually empty into the renal pelvis through the tips of the renal papillae. In each kidney, there are about 250 of the very large collecting ducts, each of which collects urine from about 4000 nephrons. Regional Differences in Nephron Structure (Length of Henle & the vascular structures) Cortical : 1. Glomeruli located in the outer cortex 2. They have short loops of Henle that penetrate only a short distance into the medulla 3. The entire tubular system is surrounded by an extensive network of peritubular capillaries Juxtamedullary Nephrons (20 to 30 % of the nephrons) : 1. glomeruli that lie deep in the renal cortex near the medulla 2.These nephrons have long loops of Henle that dip deeply into the medulla 3. long efferent arterioles extend from the glomeruli down into the outer medulla and then divide into specialized peritubular capillaries called vasa recta (this specialized network of capillaries in the medulla plays an essential role in the formation of a concentrated urine).  Urine Formation Results from Glomerular Filtration, Tubular Reabsorption, and Tubular Secretion  The rates at which different substances are excreted in the urine represent the sum of three renal processes, shown in  (1) glomerular filtration  (2) reabsorption  (3) secretion Expressed mathematically: Urinary excretion rate= Filtration rateReabsorption rate + Secretion rate Urinary excretion rate= Filtration rate- Reabsorption rate + Secretion rate Ultrafiltation : Urine formation begins when a large amount of fluid that is virtually free of protein is filtered from the glomerular capillaries into Bowman's capsule. Most substances in the plasma, except for proteins, are freely filtered, so that their concentration in the glomerular filtrate in Bowman's capsule is almost the same as in the plasma. Panel A is freely filtered by the glomerular capillaries but is neither reabsorbed nor secreted. Therefore, its excretion rate is equal to the rate at which it was filtered (such as creatinine) Panel B, the substance is freely filtered but is also partly reabsorbed from the tubules back into the blood (rate of urinary excretion < rate of filtration): electrolytes In this case, the excretion rate is calculated as the filtration rate minus the reabsorption rate. Panel C, the substance is freely filtered at the glomerular capillaries but is not excreted (comp[letly absorbed) shuch as : nutritional substances (amino acids and glucose) Panel D is freely filtered at the glomerular capillaries and is not reabsorbed, but additional quantities of this substance are secreted from the peritubular capillary blood into the renal tubules (organic acids and bases. The excretion rate in this case is calculated as filtration rate plus tubular secretion rate. Filtration, Reabsorption, and Secretion of Different Substances In general, tubular reabsorption is quantitatively more important than tubular secretion in the formation of urine, but secretion plays an important role in determining the amounts of K and H ions Most substances that must be cleared from the blood, especially the end products of metabolism such as urea, creatinine, uric acid, and urates, are poorly reabsorbed and are therefore excreted in large amounts in the urine. Why Are Large Amounts of Solutes Filtered and Then Reabsorbed by the Kidneys? One might question the wisdom of filtering such large amounts of water and solutes and then reabsorbing most of these substances. 1. One advantage of a high GFR is that it allows the kidneys to rapidly remove waste products from the body that depend primarily on glomerular filtration for their excretion. 2. A second advantage of a high GFR is that it allows all the body fluids to be filtered and processed by the kidney many times each day. Because the entire plasma volume is only about 3 liters, whereas the GFR is about 180 L/day, the entire plasma can be filtered and processed about 60 times each day. This high GFR allows the kidneys to precisely and rapidly control the volume and composition of the body fluids. Glomerular Filtration-The First Step in Urine Formation Filtrate composition s Free from proteins and devoid of cellular elements, including red blood cells. The concentrations of other constituents of the glomerular filtrate, including most salts and organic molecules, are similar to the concentrations in the plasma. Exceptions for calcium and fatty acids because of almost one half of the plasma calcium and most of the plasma fatty acids are bound to proteins GFR Is About 20 % of the Renal Plasma Flow GFR is determined by: (1) P and π (2) the capillary filtration coefficient (Kf) [the product of the permeability x A] Kf of glomerular capillaries=400 other capillaries In the average adult human, the GFR is about 125 ml/min, or 180 L/day. The fraction of the renal plasma flow that is filtered (the filtration fraction) averages about 0.2; this means that about 20 % of the plasma flowing through the kidney is filtered through the glomerular capillaries Filtration fraction : GFR/Renal plasma flow Glomerular Capillary Membrane The glomerular capillary membrane is similar to that of other capillaries, except that it has three (instead of the usual two) major layers:    Endothelium A basement membrane A layer of epithelial cells (podocytes) Together, these layers make up the filtration barrier, which, despite the three layers, filters several hundred times as much water and solutes as the usual capillary membrane. Ultra-filtration : Even with this high rate of filtration, the glomerular capillary membrane normally prevents filtration of plasma proteins. Filterability of Solutes Is Inversely Related to Their Size The glomerular capillary membrane is thicker than most other capillaries, but it is also much more porous and therefore filters fluid at a high rate. Despite the high filtration rate, the glomerular filtration barrier is selective in determining which molecules will filter, based on their size and electrical charge. Negatively Charged Large Molecules Are Filtered Less Easily Than Positively Charged Molecules of Equal Molecular Size  The molecular diameter of the plasma protein albumin is only about 6 nm, whereas the pores of the glomerular membrane are thought to be about 8 nanometers  Albumin is restricted from filtration, however, because of its negative charge and the electrostatic repulsion exerted by negative charges of the glomerular capillary wall proteoglycans  In certain kidney diseases, the negative charges on the basement membrane are lost even before there are noticeable changes in kidney histology, a condition referred to as minimal change nephropathy. As a result of this loss of negative charges on the basement membranes, some of the lower-molecularweight proteins, especially albumin, are filtered and appear in the urine, a condition known as proteinuria or albuminuria. Determinants of the GFR GFR is determined by (1) the sum of the hydrostatic and colloid osmotic forces across the glomerular membrane, which gives the net filtration pressure, and (2) the glomerular capillary filtration coefficient, Kf. Expressed mathematically, the GFR equals the product of Kf and the net filtration pressure: GFR = Kf * Net filtration pressure  The net filtration pressure represents the sum of the hydrostatic and colloid osmotic forces that either favor or oppose filtration across the glomerular capillaries .  These forces include (1) hydrostatic pressure inside the glomerular capillaries (glomerular hydrostatic pressure, PG), which promotes filtration  (2) the hydrostatic pressure in Bowman's capsule (PB) outside the capillaries, which opposes filtration  (3) the colloid osmotic pressure of the glomerular capillary plasma proteins (πG), which opposes filtration  (4) the colloid osmotic pressure of the proteins in Bowman's capsule (πB), which promotes filtration. (Under normal conditions, the concentration of protein in the glomerular filtrate is so low that the colloid osmotic pressure of the Bowman's capsule fluid is considered to be zero.)  The GFR can therefore be expressed as  Increased Glomerular Increases GFR Capillary Filtration Coefficient Increased Bowman's Capsule Hydrostatic Pressure Decreases GFR In certain pathological states associated with obstruction of the urinary tract, Bowman's capsule pressure can increase markedly, causing serious reduction of GFR. For example, precipitation of calcium or of uric acid may lead to "stones" that lodge in the urinary tract, often in the ureter, thereby obstructing outflow of the urinary tract and raising Bowman's capsule pressure. This reduces GFR and eventually can damage or even destroy the kidney unless the obstruction is relieved. تنگی آرتريول آوران : کاهش GFR ‏تنگی متوسط وابران :افزايش GFR ناشی از افزايش فشار هيدروستاتيک تنگی شديد وابران : کاهش GFRناشی از افزايش فشار اسمزی کلوئيدی  Increased Glomerular Capillary Colloid Osmotic Pressure Decreases GFR Thus, two factors that influence the glomerular capillary colloid osmotic pressure are  (1) the arterial plasma colloid osmotic pressure and (2) the fraction of plasma filtered by the glomerular capillaries (filtration fraction). Increasing the arterial plasma colloid osmotic pressure raises the glomerular capillary colloid osmotic pressure, which in turn decreases GFR. Increasing the filtration fraction also concentrates the plasma proteins and raises the glomerular colloid osmotic pressure (see Figu re 26-13). Because the filtration fraction is defined as GFR/renal plasma flow, the filtration fraction can be increased either by raising GFR or by reducing renal plasma flow. For example, a reduction in renal plasma flow with no initial change in GFR would tend to increase the filtration fraction, which would raise the glomerular capillary colloid osmotic pressure and tend to reduce GFR. For this reason, changes in renal blood flow can influence GFR independently of changes in glomerular hydrostatic pressure. With increasing renal blood flow, a lower fraction of the plasma is initially filtered out of the glomerular capillaries, causing a slower rise in the glomerular capillary colloid osmotic pressure and less inhibitory effect on GFR. Consequently, even with a constant glomerular hydrostatic pressure, a greater rate of blood flow into the glomerulus tends to increase GFR, and a lower rate of blood flow into the glomerulus tends to decrease GFR.  Increased Glomerular Capillary Hydrostatic Pressure Increases GFR  The glomerular capillary hydrostatic pressure has been estimated to be about 60 mm Hg under normal conditions. Changes in glomerular hydrostatic pressure serve as the primary means for physiologic regulation of GFR. Increases in glomerular hydrostatic pressure raise GFR, whereas decreases in glomerular hydrostatic pressure reduce GFR.  Glomerular hydrostatic pressure is determined by three variables, each of which is under physiologic control: (1) arterial pressure, (2) afferent arteriolar resistance, and (3) efferent arteriolar resistance.  Renal Blood Flow  In a 70-kg man, the combined blood flow through both kidneys is about 1100 ml/min (22 % of the CO). Considering the fact that the two kidneys constitute only about 0.4 % of the TBW, one can readily see that they receive an extremely high blood flow compared with other organs. Aims of the highly BF :  Supplies nutrients and removes waste products  The purpose of this additional flow is to supply enough plasma for the high rates of glomerular filtration that are necessary for precise regulation of body fluid volumes and solute concentrations. As might be expected, the mechanisms that regulate renal blood flow are closely linked to the control of GFR and the excretory functions of the kidneys. Renal Blood Flow and Oxygen Consumption The kidneys oxygen consumption=2 times of brain Thus, the oxygen delivered to the kidneys far exceeds their metabolic needs A large fraction of the oxygen consumed by the kidneys is related to the high rate of active sodium reabsorption by the renal tubules. Therefore, renal oxygen consumption varies in proportion to renal tubular sodium reabsorption, which in turn is closely related to GFR and the rate of sodium filtered. Determinants of Renal Blood Flow Renal blood flow is determined by the pressure gradient across the renal vasculature (the difference between renal artery and renal vein hydrostatic pressures), divided by the total renal vascular resistance:  Most of the renal vascular resistance resides in three major segments: interlobular arteries, afferent arterioles, and efferent arterioles.  Resistance of these vessels is controlled by the sympathetic nervous system, various hormones, and local internal renal control mechanisms, as discussed later.  An increase in the resistance of any of the vascular segments of the kidneys tends to reduce the renal blood flow, whereas a decrease in vascular resistance increases renal blood flow if renal artery and renal vein pressures remain constant  Although changes in arterial pressure have some influence on renal blood flow,  The kidneys have effective mechanisms for maintaining renal blood flow and GFR relatively constant over an arterial pressure range between 80 and 170 mm Hg, a process called autoregulation (myogenic and metabolic regulations).  This capacity for autoregulation occurs through mechanisms that are completely intrinsic to the kidneys  Blood Flow in the Vasa Recta of the Renal Medulla Is Very Low Compared with Flow in the Renal Cortex  Blood flow in the renal medulla accounts for only 1 to 2 % of the total renal blood flow.  Physiologic Control of Glomerular Filtration and Renal Blood Flow  The determinants of GFR include 1. the glomerular hydrostatic pressure 2. and the glomerular capillary colloid osmotic pressure. These variables, in turn, are influenced by 1. the sympathetic nervous system 2. hormones and autacoids (vasoactive substances that are released in the kidneys and act locally) Sympathetic Nervous System Activation Decreases GFR Strong activation : constrict the renal arterioles and 1. decrease renal blood flow and 2. GFR. Moderate or mild has little influence on renal blood flow and GFR. Under normal condition, sympathetic tone appears to have little influence on renal blood flow. Hormonal and Autacoid Control of Renal Circulation 1. Norepinephrine 2. Epinephrine 3. Endothelin Constrict Renal Blood Vessels and Decrease GFR. NE and Epinephrine (severe hemorrhage) constrict afferent and efferent arterioles GFR and RBF Endothelin (vascular injury, such as toxemia of pregnancy, acute renal failure, and chronic uremia) renal vasoconstriction and GFR Prostaglandins and Bradykinin Tend to Increase GFR. PGE2 and PGI2 and bradykinin cause 1. Vasodilation 2. increased renal blood flow 3. and GFR These agents # sympathetic effect Under stressful conditions, such as volume depletion or after surgery, the administration of nonsteroidal anti-inflammatory agents, such as aspirin, that inhibit prostaglandin synthesis may cause significant reductions in GFR. Autoregulation of GFR and Renal Blood Flow Feedback mechanisms intrinsic to the kidneys normally keep the RBF and GFR relatively constant, despite marked changes in arterial blood pressure. This relative constancy of GFR and renal blood flow is referred to as autoregulation. In the kidneys, the normal blood flow is much higher than that required for these functions. The major function of autoregulation in the kidneys is to maintain a relatively constant GFR and to allow precise control of renal excretion of water and solutes Figure 26-16 Autoregulation of renal blood flow and glomerular filtration rate but lack of autoregulation of urine flow during changes in renal arterial pressure. The GFR autoregulated relatively considerable fluctuations normally remains (that remains is, constant), despite arterial pressure that occur person's usual activities during a (a decrease in arterial pressure to as low as 75 mm Hg or an increase to as high as 160 mm Hg changes GFR only a few percentage points). Importance of Preventing GFR Extreme Autoregulation Changes in in Renal Excretion The autoregulatory mechanisms of the kidney are not 100 per potentially excretion cent perfect, large of but changes water and in they GFR solutes do prevent and that renal would otherwise occur with changes in blood pressure. Normally, GFR is about 180 L/day and tubular reabsorption is 178.5 L/day, leaving 1.5 L/day of fluid to be excreted in the urine. In the absence of autoregulation, a relatively small increase in blood pressure (from 100 to 125 mm Hg) would cause a similar 25 per cent increase in GFR (from about 180 to 225 L/day). If tubular reabsorption remained constant at 178.5 L/day, increase the urine flow to 46.5 L/day this would But in reality, such a change in arterial pressure exerts much less of an effect on urine volume for two reasons: (1) renal autoregulation prevents large changes in GFR that would otherwise occur, and (2) there are additional adaptive mechanisms in the renal tubules that allow them to increase their reabsorption rate when GFR rises, a phenomenon referred to as glomerulotubular balance Role of Tubuloglomerular Feedback in Autoregulation of GFR  To perform the function of autoregulation, the kidneys have a feedback mechanism that links changes in NaCl concentration at the macula densa with the control of renal arteriolar resistance. This feedback helps ensure a relatively constant delivery of NaCl to the distal tubule and helps prevent spurious fluctuations in renal excretion that would otherwise occur. The juxtaglomerular complex consists of 1- macula densa cells in the initial portion of the distal tubule and 2- juxtaglomerular cells in the walls of the afferent and efferent arterioles. The macula densa is a specialized group of epithelial cells in the distal tubules that comes in close contact with the afferent and efferent arterioles. The macula densa cells contain Golgi apparatus, which are intracellular secretory organelles directed toward the arterioles, suggesting that these cells may be secreting a substance toward the arterioles. Decreased Macula Densa NaCl Causes Dilation of Afferent Arterioles and Increased Renin Release The macula densa cells sense changes in volume delivery to the distal tubule. GFR flow rate in the loop of Henle reabsorption NaCl NaCl at the macula densa cells signal from the macula densa that has two effects initiates a renin Angiotensinogen angiotensin II ACE(Lung) angiotensin I Angiotensin II constricts the efferent arterioles, thereby increasing PG and returning GFR toward normal.  Blockade of Angiotensin II Formation Further Reduces GFR During Renal Hypoperfusion As discussed earlier, a preferential constrictor action of angio II on efferent arterioles helps prevent serious reductions in PG and GFR when renal perfusion pressure falls below normal. The administration of drugs that block the formation of angio II (inhibitors) or that block the action of angio II (angio II antagonists) causes greater reductions in GFR than usual when the renal arterial pressure falls below normal. Therefore, an important complication of using these drugs to treat patients who have hypertension because of renal artery stenosis (partial blockage of the renal artery) is a severe decrease in GFR that can, in some cases, cause acute renal failure. Nevertheless, angiotensin II-blocking drugs can be useful therapeutic agents in many patients with hypertension, congestive heart failure, and other conditions, as long as they are monitored to ensure that severe decreases in GFR do not occur. Other Factors That Increase Renal Blood Flow and GFR: High Protein Intake and Increased Blood Glucose Tubular Reabsorption Is Selective and Quantitatively Large Filtration = Glomerular filtration rate* Plasma concentration Proximal tubule Reabsorption & secretion Concentrations of Solutes Along the Proximal Tubule 20% Solute and Water transport in the Loop of Henle 0 mv inhibition Early distal tubule Approximately 5% of the filtered load of sodium chloride is reabsorbed in the early distal tubule. The sodium-chloride co-transporter moves inhibition Early distal tubule Late distal tubule Principal C. Reabsorb Na and Secrete K. Medullary collecting duct Urine concentration اسالم بر خالف مذاهب دیگری که توجیه کننده ی فقر را مناسبات زندگی اجتماعی میدانند ،بزرگترین آموزش یافته ی مکتبش ابوذر میگوید“ :وقتی فقر وارد خانه ای میشود ،دین از درب دیگر خارج میشود” و یا پیامبر اسالم حضرت محمد (ص) که بنیانگذار مکتبی است که همه ما مسلمانان به آن اعتقاد راسخ داریم چه شیوا و ساده بیان فرموده است: “من ال معاش له ال معاد له” کسی که زندگی مادی ندارد زندگی معنوی هم نخواهد داشت. ‏چون؛ شکم خالی هیچ ندارد ،جامعه ای که دچار کمبود اقتصادی و مادی است مسلمًا کمبود های معنوی بسیاری خواهد داشت و آنچه را که در جامعه های فقیر ،آنرا اخالق و مذهب می نامند ،متاسفانه معنویت در آن جایی ندارد. میخواهم بگویم؛ فقر همه جا سر میکشد … فقر ،گرسنگی نیست ،عریانی هم نیست …فقر ،حتی گاهی زیر شمش های طال خود را پنهان میکند… فقر ،چیزی را “نداشتن” است ؛ ولی آن چیز پول نیست ؛ طال و غذا هم نیست … فقر ،ذهن ها را مبتال میکند … فقر ،اعجوبه ایست که بشکه های نفت در عربستان را تا ته سر میکشد … فقر ،همان گرد و خاکی است که بر کتابهای فروش نرفته ی یک کتابفروشی می نشیند … فقر ،تیغه های برنده ماشین بازیافت است که روزنامه های برگشتی را خرد میکند … فقر ،کتیبه ی سه هزار ساله ای است که روی آن یادگاری نوشته اند … فقر ،پوست موزی است که از پنجره یک اتومبیل به خیابان انداخته میشود … فقر ،همه جا سر میکشد … فقر ،شب را “بی غذا” سر کردن نیست … فقر ،روز را “بی اندیشه” سر کردن است … مایع خارج سلولی..... کلسیم و، تنظیم غلظت پتاسیم میلی ایکی واالن در لیتر4/2 غلظت طبیعی پتاسیم پالسما برابر با-  افزایش پتاسیم پالسما منجر به ایست قلبی می گردد-  توزیع پتاسیم در بخش های مختلف به ترتیب ذیل است ICF=98%  ECF=2%  بنابراین سلول ها می توانند در ایجاد تعادل پتاسیم یعنی هوموستاز آن نقش مهمی داشته باشند  An overflow site for excess ECF potassium during hyperkalemia  A resource of potassium during hypokalemia  Therefore, redistribution of k+ between the intra- and extracellular compartments provides a first line of defense against changes in ECF potassium concentration فاکتورهای افزایش دهنده جذب سلولی پتاسیم انسولین ،آلدوسترون ،تحریک بتا آدرنرژیک و آلکالوز ‏فاکتورهای کاهش دهنده جذب سلولی پتاسیم دیابت ،آدیسون ،بلوک بتا آدرنرژیک ،تخریب سلولی (سلول خونی و عضالنی) ، ورزش سنگین و افزایش یافتن اسموالریته خارج سلولی س :در صورت عدم وجود مکانیزم های تنظیمی دریافت مقدار 100ملی ایکی واالن پتاسیم چه تاثیری بر پتاسیم پالسما و عملکرد بدن داشت؟  ANG II Has Many Effects                     Angiotensin II has significant effects on fluid balance and blood pressure beyond stimulating aldosterone secretion, underscoring the integrated functions of the renal and cardiovascular systems. ANG II increases blood pressure both directly and indirectly through four additional pathways (Fig. 20.10): 1 ANG II increases vasopressin secretion. ANG II receptors in the hypothalamus initiate this reflex. Fluid retention in the kidney under the influence of vasopressin helps conserve blood volume, thereby maintaining blood pressure. 2 ANG II stimulates thirst. Fluid ingestion is a behavioral response that expands blood volume and raises blood pressure. 3 ANG II is one of the most potent vasoconstrictors known in humans. Vasoconstriction causes blood pressure to increase without a change in blood volume. 4 Activation of ANG II receptors in the cardiovascular control center increases sympathetic output to the heart and blood vessels. Sympathetic stimulation increases cardiac output and vasoconstriction, both of which increase blood pressure. 5 ANG II increases proximal tubule Na reabsorption. ANG II stimulates an apical transporter, the Na -H exchanger (NHE). Sodium reabsorption in the proximal tubule is followed by water reabsorption, so the net effe + + + :اختالالت اسید و باز اسیدوز متابولیک منجر به هیپرکالمی آلکالوز متابولیک منجر به هیپوکالمی علل احتمالی هیپرکالمی در اسیدوز تاثیر منفی یون هیدروژن تجمع یافته بر فعالیت پمپ پتاسیم-سدیم  Acute acidosis: a decrease in potassium secretion due to Na/K pump inhibition  Chronic acidosis: an increase in potassium secretion due to inhibition of reabsorption of water and sodium in proximal tubule lead to increase delivery them to distal portions of nephron which should reabsorb in these segments and also an increase in GFR. مروری بر دفع پتاسیم هر چه مقدار فیلتراسیون گلومرولی بیشتر باشد میزان دفع؟ ‏میزان بازجذب پتاسیم در لوله نزدیک 65درصد و بخش ضخیم هنله 27درصد ‏ترشح پتاسیم که سلول های اصلی متخصص این امر بوده و در حالت طبیعی روزانه 31میلی اکی واالن برابر 4درصد از پتاسیم را ترشح می کنند. -در صورتی که روزانه مقدار دریافت پتاسیم 100میلی اکیواالن باشد کلیه ها باید حدود 92 درصد آن را دفع کنند و از این مقدار 31درصد در بخش های انتهایی نفرون جمع آوری می گردد. -حدود 8میلی اکیواالن از طریق مدفوع دفع می گردد. -نکته 90درصد سلول های توبول دور و مجاری جمع کننده سلول اصلی هستند. ‏ترشح پتاسیم بوسیله سلول های اصلی یک فرآیند دو مرحله است -1ورود پتاسیم به سلول از طیق غشا قاعده ای بوسیله پمپ سدیم-پتاسیم -2خروج پتاسیم از سلول های فوق از طریق غشا لومینال  Luminal membranes of principal cells are highly permeable to potassium. They have epithelial potassium channels in this membrane.   Intercalated cells can reabsorb potassium during potassium depletion.  It maybe occurs through K-H ATPase located in the luminal membrane.   Key factors stimulate potassium secretion by principal cells  [K+ ] 2. Aldosterone increment and 3. High flow rate of tubular fluid ECF   The most potent releaser of aldosterone is hyperkalemia.  If potassium concentration increases from 3.5 to 6, plasma aldosterone levels increase up to 10 times. Control of renal calcium excretion and calcium ECF concentration  [Ca]ECF=2.4 meq/L  50% as ionized or free form  40%= bound to plasma proteins  10%=complex with phosphate and citrate.  Hypocalcemia leads to neuronal hyper-excitability (Tetany)   Hypercalcemia leads to decrease neuronal excitability (Coma)  Unlike other ions such as sodium, potassium and …, a large share of calcium excretion occurs in the feces.  PTH Day to day regulation of calcium concentration is mediated in large part by the effect of PTH on bone resorption This hormone 1. Stimulate bone resorption 2. Activate vitamin D and 3. directly increases renal tubular calcium reabsorption Control of renal calcium ‏excretion چون کلسیم ترشح نمی گردد بنابراین میزان دفع ان از فرمول ذیل محاسبه می گردد ‏ Renal calcium excretion=Ca filtered-Ca reabsorbed 99درصد کلسیم به ترتیب در لوله نزدیک ( ،)65ضخیم هنله ()25-30و لوله دور و جمع کننده ( )4-9بازجذب می گردد. عوامل افزایش دهنده بازجذب کلسیم ‏PTH, Hypocalcemia, hypotention, hyperphostamemia, ‏metabolic acidosis, VitD ‏عوامل کاهش دهنده بازجذب کلسیم ‏عکس موارد فوق ‏در زمان هیپرتانسیون یا افزایش حجم مایع خارج سلولی به دلیل باال بودن GFRو افزایش سرعت مایع توبولی بازجذب؟؟؟؟ دفع فسفات از یک سیستم لبریز شونده تبعیت می کند توبول های کلیوی برای بازجذب این ترکیب کاینیتیک حداکثر اشباع (0.1 )mMنشان می دهند. ‏هرگاه غلظت پالسمایی از 0/8میلی موالر بیشتر شود در ادرار ظاهر می گردد. )1000 CC (Plasma 0.8mM )125 CC (GFR 0.1 mM PTHنقش کلیدی در دفع فسفات دارد ‏منیزیم ‏محل بازجذب توبول نزدیک ( ،)25ضخیم هنله ( )65و لوله دور 5درصد در شرایط هیپرمنیزمی ،هیپرکلسمی و افزایش حجم ECFمیزان دفع منیزیم افزایش می یابد. مکانیزم های کلیوی کنترل حجم مایع خارج سلولی ‏حجم مایع خارج سلولی به وسیله تعادل بین دریافت آب و نمک تعیین می گردد. ‏دفع سدیم به وسیله دو متغیر GFR-1و -2میزان بازجذب کنترل می گردد. ‏Sodium excretion= GFR-Reabsorption. ‏درصورتی که اختاللی هریک از دو متغیر فوق را تحت تاثیر قرار دهد مکانیزم های بافری وارد عمل می گردد ‏Glomerulotubular balance ‏Macula densa feedback اهمیت دیورز و ناتریورز فشاری در تنظیم تعادل آب و سدیم ‏تعریف دیورز؟ ‏به اثر فشار خون بر دفع سدیم ناتریورز فشاری و بر دفع آب دیورز فشاری گویند. ‏دو پدیده فوق مکانیزم های فیدبکی کلیدی بدن برای تنظیم مایعات بدن و فشار شریانی می باشند ‏افزایش دریافت آب و نمک :افزایش حجم مایع : ECFافزایش حجم خون: ‏افزایش میانگین فشار پرشدگی عروقی :افزایش بازگشت وریدی :افزایش برون ده قلبی: افزایش فشار خون :افزایش : GFRدیورز فشاری ‏بنابراین تغییرات بزرگ در دریافت مایع و نمک در شرایط فیزیولوژیک تاثیر کمی بر حجم خون ،فشار خون و حجم ECFخواهد داشت. Distribution of ECF between the ISF ‏and plasma در صورتی که مقدار کمی مایع به دلیل نوشیدن زیاد یا کاهش برون ده کلیوی در خون تجمع یابد حدود 20-30درصد آن پس از مدتی به ISFوارد شده مابقی در سیستم عروقی باقی خواهد ماند ‏ولی اگر میزان تجمع مایع زیاد باشد 50درصد از آن به ISFوارد می شود که این مساله باعث ایجاد ادم می گردد ولی از طرفی ورود این بار اضافی به فضای میان بافتی در شرایط تحت حاد از Overloadقلب می کاهد (نقش کاردیوپروتکتیو). Neuronal and hormonal mechanisms usually act in concert with the pressure natriuresis and pressure diuresis, making them more effective in minimizing the changes in blood volume, ECF volume and arterial pressure that occur in response to day-to-day challenges. سیستم عصبی سمپاتیک رفلکس گیرنده بارورسپتو شریانی و گیرنده حجمی:کنترل دفع کلیوی Hemorrhage: a decrease in pressure of pulmonary blood vessel: activation of sympathetic system leads to 1. Vasoconstricing the afferent arteriole 2. decrease GFR 3. Activation of RAS 4. And ultimately increase tubular reabsorption (water and salt) 5. افزایش های فارماکولوژیک یا پاتولوژیک Angio2تاثیر قابل مالحظه ای بر حجم ECFندارد زیرا ‏افزایش آنژیو :2احتباس آب و سدیم توسط کلیه ها :افزایش حجم : ECFافزایش : BPدیورز و ناتریورز فشاری :تصحیح حجم خارج سلولی. ‏آلدوسترون نیز با بازجذب سدیم منجر به احتباس آب و سدیم و دفع پتاسیم می گردد. ‏فرار آلدوسترونی: ‏در صورت انفیوژن آلدوسترون یا تومور غده فوق کلیه (سندرم کن ) افزایش بازجذب توبولی سدیم و کاهش دفع ادراری آن گذرا خواهد بود .زیرا: ‏یک تا سه روز پس از احتباس آب و سدیم :افزایش حجم ECFبه میزان 10-15درصد: افزایش هم زمان : BPدیورز فشاری (در این زمان کلیه ها از احتباس آب و نمک فرار کرده و از آن پس مقادیر ورودی با خروجی برابر خواهد بود) فقدان آلدوسترون یا کاهش یافتن ترشح آن :افت شدید حجم ECF ‏ The most important role of aldosterone is to ‏maintain the volume of ECF در شرایط فیزیولوژیک محرومیت از آب به مدت 24-48ساعت به دلیل افزایش ترشح ADHتاثیر اندکی بر حجم ECFو BPدارد. ‏افزایش ADHنیز تاثیر اندکی بر بر حجم ECFو BPدارد که به دلیل ایجاد دیورز فشاری می باشد. ‏ولی افزایش ADHمی تواند منجر به هیپوناترمی گردد (هم رقیق شدن سطح پالسمایی سدیم به دلیل افزایش بازجذب آب و هم ایجاد دیورز فشاری) Regulation of Acid-Base Balance Definitions : Acids : Molecules can release hydrogen ions in solutions (HCl & H2CO3) Bases : A base is an ion or a molecule that can accept an H+. For example, HCO3 & HPO4 The proteins in the body also function as bases, because some of the amino acids that make up proteins have net negative charges that readily accept H+. The protein hemoglobin in the RBCs and proteins in the other cells of the body are among the most important of the body’s bases. انواع اسيدها )1فرار :اسيدهائی که می توانند توسط ريه ها دفع شوند ()H2CO3 )2غيرفرار :به طور عمده توسط متابوليسم پروتئين ها توليد می شوند و نمی توانند توسط ريه ها دفع شوند mEq 80اسيد غيرفرار توليد می کند بدن روزانه حدود (از متابوليسم پروتئين ها که فقط توسط کليه ها بايد دفع گردد The terms base and alkali are often used synonymously An alkali is a molecule formed by the combination of one or more of the alkaline metals—sodium, potassium, lithium, and so forth—with a highly basic ion such as a hydroxyl ion (OH–). The base portion of these molecules reacts quickly with H+ to remove it from solution; they are, therefore, typical bases. For similar reasons, the term alkalosis refers to excess removal of H+ from the body fluids, in contrast to the excess addition of H+, which is referred to as acidosis. Alkalosis pH>7.4, Acidosis pH<7.4 Strong and Weak Acids and Bases A strong acid is one that rapidly dissociates and releases especially large amounts of H+ in solution (HCl). Weak acids …………H2CO3 A strong base is one that reacts rapidly and strongly with H+ and, therefore, quickly removes these from a solution (example is OH–, which reacts with H+ to form water (H2O) A typical weak base is HCO3 because it binds with H+ much more weakly than does OH– Most of the acids and bases in the ECF that are involved in normal acid-base regulation are weak acids and bases Body buffer systems Buffer systems do not eliminate H+ from or add them to the body but only keep them tied up until balance can be reestablished. 1. Chemical B. : a few seconds 2. Respiratory B. system : a few minutes (acts within a few minutes to eliminate CO2 and, therefore, H2CO3 from the body) . 3. Kidneys B. (a few hours to days) : can eliminate the excess acid or base from the body, the strongest system H ions origin : In the body : 0.00004 mEq/L (40 nEq/L). Produced during or ingested : 80 mEq/day (Without buffering, the daily production and ingestion of acids would cause huge changes in body fluid H+ concentration) Buffering of Hydrogen Ions in the Body Fluids A buffer is any substance that can reversibly bind H+. The general form of the buffering reaction is Factors that determinates the ability of buffer system 1.PK system 2.Buffer ingredients concentration 3.Regulation of ingredients concentration by other system Bicarbonate Buffer System The bicarbonate buffer system consists of a water solution that contains two ingredients: (1) a weak acid, H2CO3, and (2) a bicarbonate salt, such as NaHCO3. H2CO3 is formed in the body by the reaction of CO2 with H2O. CA CO2 + H2O H2CO3 H2CO3 H+ + HCO3Carbonic anhydrase is especially abundant in the walls of the lung alveoli, where CO2 is released & also present in the epithelial cells of the renal tubules, where CO2 reacts with H2O to form H2CO3. When a strong acid such as HCl is added to the bicarbonate buffer solution, the increased H+ released from the acid (HCl H + Cl) is buffered by HCO3 HCl + NaHCO3 NaCl + H2CO3 As a result, more H2CO3 is formed, causing increased CO2 and H2O production In this case, the OH– from the NaOH combines with H2CO3 to form additional HCO3 . Thus, the weak base NaHCO3 replaces the strong base NaOH. At the same time, the concentration of H2CO3 decreases (because reacts with NaOH), causing more CO2 to combine with H2O to replace the H2CO3 The net result, therefore, is a tendency for the CO2 levels in the blood to decrease, but the decreased CO2 in the blood inhibits respiration and decreases the rateof CO2 expiration.The rise in blood HCO3 that occurs is compensated for by increased renal excretion of HCO3 Bicarbonate Buffer System 1. PK = 6.1 2. Concentration of ingredients regulates by kidneys and respiratory system Thus, Bicarbonate Buffer System is the most important and strongest system in ECF Phosphate Buffer System 1. The phosphate buffer system is not important as an ECF buffer 2. It plays a major role in buffering renal tubular fluid and ICF 3. The main elements of the phosphate buffer system are H2PO4 and HPO4 When a strong acid such as HCl is added to a mixture of these two substances, the hydrogen is accepted by the base HPO4 and converted to H2PO4 When a strong base, such as NaOH, is added to the buffer system, the OH is buffered by the H2PO4to form additional amounts of HPO4 + H2O. Phosphate Buffer System 1. pK = 6.8 which is not far from the normal pH = 7.4 in the body fluids 2. Its concentration in the ECF is low (about 8 % of the concentration of the bicarbonate buffer) In contrast to its rather insignificant role as an extracellular buffer , the phosphate buffer is especially important in the tubular fluids of the kidneys and intracellular fluid 1. It usually becomes greatly concentrated in the tubules 2. the tubular fluid usually has a considerably lower pH than the ECF does, bringing the operating range of the buffer closer to the pK (6.8) of the system 3.The concentration of phosphate in this fluid (ICF) is many times that in the ECF 4 . Also, the pH of intracellular fluid is < that of ECF and therefore is usually closer to the pK of the phosphate buffer system compared with the ECF. Proteins: Important Intracellular Buffers Proteins are among the most plentiful buffers in the body because of their high concentrations, especially within the cells. The pH of the cells, although slightly < in the ECF, nevertheless changes approximately in proportion to ECF pH changes. There is a slight amount of diffusion of H+ and HCO3 through the cell membrane, although these ions require several hours to come to equilibrium with the extracellular fluid, except for rapid equilibrium that occurs in the red blood cells. CO2, however, can rapidly diffuse through all the cell membranes. This diffusion of the elements of the bicarbonate buffer system causes the pH in intracellular fluid to change when there are changes in extracellular pH. For this reason, the buffer systems within the cells help prevent changes in the pH of ECF but may take several hours to become maximally effective. In the red blood cell, hemoglobin (Hb) is an important buffer, as follows: Approximately 60 to 70 % of the total chemical buffering of the body fluids is inside the cells, and most of this results from the intracellular proteins. In addition to the high concentration of proteins in the cells, another factor that contributes to their buffering power is the fact that the pKs of many of these protein systems are fairly close to 7.4. Respiratory Regulation of Acid-Base Balance The second line of defense against acid-base disturbances is control of ECF CO2 concentration by the lungs. Ventilation [H+] [ECF] Ventilation [H+] CO2 Elimination [ECF] CO2 Elimination Agents that determine the concentration of CO2 1. metabolic formation rate 2. pulmonary ventilation. Increasing alveolar ventilation to about twice normal raises the pH of the ECF by about 0.23 (PH 7.4 7.63) reducing the ventilation to one fourth normal reduces the pH to 6.95. تاثير غلظت يون هيدروژن بر تهويه حبابچه ای Feedback Control of Hydrogen Ion Concentration by the Respiratory System کارآئی کنترل تنفسی غلظت يون هيدروژن : کنترل تنفسی کامال قادر به برگرداندن Phبه ميزان طبيعی نيست يعنی اينکه موثر بودن اين سيستم به ميزان 50تا 75درصد است. به عنوان مثال قادر است PH =7را به ميزان 0/2تا 0/3ارتقاء دهد يعنی PH مقايسه قدرت سيستم بافری سيستم تنفسی با سيستم بافرهای شيميائی بدن ‏Buffer potency comparison ‏respiratory system >> chemical ‏system قدرت بافری سيستم تنفسی يک تا دو برابر بيشتر از قدرت بافری تمام بافرهای ديگر موجود در ECFاست کنترل کليوی تعادل اسيد – باز کليه ها با تغيير دادن PHادرار PH ،مايعات خارج سلولی را تنظيم می کنند در شرايط اسيدوز دفع ادرار اسيدی :بازجذب بيشتر HCO3و ترشح بيشتر يون H در شرايط آلکالوز دفع ادرار بازی :بازجذب کمتر HCO3و کاهش ترشح يون H مکانيزم های کليوی برای تنظيم غلظت يون هيدروژن ECF )1ترشح يون های هيدروژن )2بازجذب يون های بيکربنات فيلتره شده )3توليد يون های بيکربنات جديد Phosphate Buffer System Carries Excess Hydrogen Ions into the Urine and Generates New Bicarbonate 1.HPO4 and H2PO4 become concentrated in the tubular fluid because of their relatively poor reabsorption 2. Under normal conditions, the urine is slightly acidic, and the urine pH is near the pK = 6.8 of the phosphate buffer system. whenever an H secreted into the tubular lumen combines with a buffer other than HCO3, the net effect is addition of a newHCO3 to the blood. Under normal conditions, much of the filtered phosphate is reabsorbed, and only about 30 to 40 mEq/day is available for buffering H+. Therefore, much of the buffering of excess H+ in the tubular fluid in acidosis occurs through the ammonia buffer system. Excretion of Excess Hydrogen Ions and Generation of New Bicarbonate by the Ammonia Buffer System A second buffer system in the tubular fluid that is even more important quantitatively than the phosphate buffer system is composed of ammonia (NH3) and the ammonium ion (NH4). Ammonium ion is synthesized from glutamine, which comes mainly from the metabolism of amino acids in the liver. The glutamine delivered to the kidneys is transported into the epithelial cells of the proximal tubules, thick ascending limb of the loop of Henle, and distal tubules (Figure 30–8). Once inside the cell, each molecule of glutamine is metabolized in a series of reactions to ultimately form two NH4 and two HCO3. The HCO3 generated by this process constitutes new bicarbonate. In the collecting tubules The addition of NH4 to the tubular fluids occurs through a different mechanism (Figure 30–9). Here, H is secreted by the tubular membrane into the lumen, where it combines with NH3 to form NH4, which is then excreted. The collecting ducts are permeable to NH3, which can easily diffuse into the tubular lumen. However, the luminal membrane of this part of the tubules is much less permeable to NH4; therefore, once the H has reacted with NH3 to form NH4, the NH4 is trapped in the tubular lumen and eliminated in the urine. For each NH4 excreted, a new HCO3 is generated and added to the blood. Chronic Acidosis Increases NH4 Excretion One of the most important features of the renal ammonium-ammonia buffer system is that it is subject to physiologic control. [H+] [ECF] formation of NH4 stimulates renal glutamine metabolism New HCO3 to be used in H buffering; A decrease in H+ concentration has the opposite effect. Under normal conditions The amount of H eliminated by the ammonia buffer system accounts for about 50 per cent of the acid excreted and 50 per cent of the new HCO3 generated by the kidneys. Chronic acidosis The rate of NH4 excretion can increase to as much as 500 mEq/day. Therefore, with chronic acidosis, the dominant mechanism by which acid is eliminated is excretion of NH4. This also provides the most important mechanism for generating new bicarbonate during chronic acidosis.

62,000 تومان