Ce diaporama a bien été signalé.
Le téléchargement de votre SlideShare est en cours. ×
Renal Physiology
6. Renal Physiology 2
6. Renal Physiology 3
1. Introduction
The urinary system includes those organs of the body that
produce and eliminate urin...
Prochain SlideShare
Renal physiology-1
Renal physiology-1
Chargement dans…3

Consultez-les par la suite

1 sur 76 Publicité

Plus De Contenu Connexe

Plus récents (20)



  1. 1. 6. Renal Physiology
  2. 2. 6. Renal Physiology 2
  3. 3. 6. Renal Physiology 3 1. Introduction The urinary system includes those organs of the body that produce and eliminate urine (a combination of water and waste products that passes out of the body as fluid) The urinary system consists of the kidneys, ureters, urinary bladder, and urethra.  The kidneys form the urine and account for the other functions attributed to the urinary system.  The ureters carry the urine away from kidneys to the urinary bladder.  Urinary bladder is a temporary reservoir for the urine.  The urethra is a tubular structure that carries the urine from the urinary bladder to the outside. FUNCTIONS OF KIDNEY List the functions of Kidney. CU May 16, RU MAY 18,NOV 16, SUST Jan 16, DU Nov 17, May 16, Jan17, 16, CU Jan 15, DU Jan 15, Ju-1 2 Discuss the functions of kidney. DU Ja-10, 09. 08, Mention four important functions of kidney. DU Ju-13 Give the function of kidney in homeostasis Write the endocrine functions of kidney. DU Jan 14, Jul 11 1. Formation of urine. 2. Excretion of metabolic waste products and foreign chemicals: • Urea, Uric acids, Creatinine, Urates. • Bilirubin. • Toxic & foreign bodies e.g. drugs • Na+ , K+ , Ca++ , Mg++ , HCO3 - , PO4 -- , water etc. 3. Endocrine functions: • Secretion of renin which helps in conversion of Angiotersinogen to Angiotensin-1. It helps in blood pressure regulation. • Formation of active from of vitamin D (1,25 dihydroxycholecalciferol) under the influence of parathyroid hormone. • Formation of Erythropoietin. Thus helps in erythropoiesis. • It also produces Prostaglandins & Thromboxanes. 4. Metabolic functions: • Transamination and deamination of amino acids • Gluconeogenesis • Metabolites of various hormones. 5. Reabsorption of substances: • Glucose • Amino acid • Electrolytes e.g. Na+, K+, HCO3-, PO4 etc. 6. Regulatory functions: Regulation of- • Water & Electrolytes balance.
  4. 4. 6. Renal Physiology 4 • Body fluid osmolality and electrolyte concentrations • Acid-base balance. • arterial pressure (Reference: Guyton, 13th , 323 and others) Excretion Excretion is the process by which metabolic waste and other toxic materials is eliminated from the body.. Excretory organs are: 1. kidney- main organ of excretion 2. Liver 3. Skin - skin eliminates metabolic wastes like urea and lactic acid through sweating. 4. Lungs - expel carbon dioxide. 5. Salivary System Viva Q Q. Explain- feces is not an excretory product, - In strict biological terminology, undigested food expelled in the feces is not considered to be an excretory product, since it is not metabolic waste. Substances secreted into the bile and then eliminated in the feces are considered to be excreted, however. MCQ Q. Kidney function includes-(DU-15Ju) a. Excretion of metabolic waste products b. Production of antbody c. Water balance d. Regulation of blood pressure e. Temperature regulation Ans. a-T, b-F, c-T, d-T, e-T Q. The kidney secretes-(DU-13, 12 Ju) a. renin b. erythropoietin c. 1,25-dihydroxy choleaclciferol d. angiotensin I e. vasopressin Ans. a-T, b-T, c-T, d-F, e-F Q. Kidney functions include-(DU-13,12J) a. excretion of metabolic waste products b. production of antibody c. water balance d. regulation of blood pressure e. temperature regulation Ans. a-T, b-F, c-T, d-T, e-F Q. Kidney function includes-(DU-10J) a. excretion of metabolic waste products (T) b. production of antibody (F) c. water balance (T) d. regulation of blood pressure (T) e. temperature regulation (T) Q. Kidney produces-(DU-10Ju) a. Eqinephrine (F) b. Calcitriol (T) c. angiotensin-II (F) d. calcitonin (F) e. calmodulin (F) Q. Kidneys regulate arterial pressure by-(Du-14Ju) a. vasoactive factros b. excreating water c. ADH d. renin angiotensin mechanism e. excreting K+ Ans. a-F, b-T, c-F, d-T, e-F Q. Renin secretion is stimulated by-(DU-14Ju) a. cardiac failure b. low Na+ in the proximal tubule c. sympathetic stimulation d. high K+ in proximal tubule e. cortisol Ans. a-T, b-T, c-T, d-F, e-F Q. Kidneys regulate arterial pressure by-(DU-13J) a. exreting Na+ b. reabsorbinfg water c. excreating urea d. secreting renin e. renin angiotensin mechanism Ans. a-T, b-T, c-F, d-T, e-T Q. The renin angiotensin aldosterone system regulates- (DU-10J) a. Potassium balance (T) b. sodium balance (T) c. nitrogen balance (F) d. fluid balance (T) e. calcium balance (F) Q. Kidney functions include (DU May 16)
  5. 5. 6. Renal Physiology 5 a. excretion of metabolic waste products b. production of antibody c. water balance d. regulation of blood pressure e. regulations of body temperature Ans. a-T, b-F, c-T, d-T, e-F Q. The Kidney functions include (DU Jan17) – a. regulate blood volume. b. participate in the synthesis of vit C. d. release angiotensin II d. release erythropoietin. e. help to regulate blood pressure Ans. a) T b) F c) F d)T e) T 2. Nephron Definition: Define nephron. CU Nov 16, RU JUL 15, JAN13 It is the structural & functional unit of kidney. Number : Each kidney consists of about 1 million nephrons. (Guyton, 13th, 325) Structure/parts: Draw and label the parts of a nephron. CU May 16, SUST Jan 16, DU Nov16, Ju-13, Ja-15, 10, 09, RU May 16, JUL 15, JAN12, 11, 09 , SUST Jan 12 It consists of two parts. (a) Renal corpuscles- i. Glomerulus ii. Bowman”s capsule (b) Renal tubule i. Proximal Convoluted Tubule (PCT)
  6. 6. 6. Renal Physiology 6 ii. Loop of Henle (LH) iii. Distal Convoluted Tubule (DCT) iv. Collecting tubule (CT) v. Collecting duct (CD) Figure: parts of nephron GLOMERULUS What is glomerulus? RU JAN 14 Draw & label a glomerular membrane. DU Jan-13, 12, CU May 15, Jul 15, SUST Jul 13 Definition: It is a tuft of capillaries through which large amounts of fluid are filtered from the blood. (Guyton) Structure Name the layers of glomerular capillary membrane through which filtration occurs. RU JAN 15 The glomerular filtration barrier is formed by 3 layers
  7. 7. 6. Renal Physiology 7 1. Endothelium of the glomerular capillaries: • fenestrated, • Pores are 70-90 nm in diameter. 2. Basement membrane (BM): • Does not contain visible gaps or pores. • stellate cells called mesangial cells are located between the basal lamina and the endothelium. Mesangial cells are contractile and play a role in the regulation of glomerular filtration. They also secrete various substances, take up immune complexes and are involved in the production of glomerular disease. The BM contains three layers: 3. Epithelium of the Bowman’s capsule: • specialized epithelium • Made up of podocytes overlying the capillaries. • The cells of the epithelium (podocytes) have numerous pseudopodia that interdigitate to form filtration slits along the capillary wall. The slits are approximately 25 nm wide, and a thin membrane closes each. Function Permits the free passage of neutral substances up to 6 nm. However, the charges on molecules as well as their diameters affect their passage into Bowman’s capsule. (Guyton, 13th , 335) Why high filtration rate occurs across the glomerular capillary membrane? SUST Jul 13 Why is glomerular capillary is more permeable than other capillaries? Answer: Because 1. The capillary endothelium is perforated by thousands of small holes called fenestrae.. 2. The basement membrane has large spaces through which large amounts of water and small solutes can filter. (Guyton, 13th , 335) Layer Location Composition Function Lamina rara interna Adjacent to endothelial cells Heparan sulfate Blocks by charge Lamina densa Dark central zone Type 4 collagen and laminin Blocks by size (MW > 69,000) Lamina rara externa Adjacent to podocyte processes Heparan sulfate Blocks by charge
  8. 8. 6. Renal Physiology 8 FUNCTION OF NEPHRON • Glomerular filtration • Tubular reabsorption – glucose, amino acid • Tubular secretion- H+ , K+ and HCO- 3 (Reference: Guyton) FUNCTIONS OF THE DIFFERENT PARTS OF THE RENAL TUBULE Give the function of DCT. SUST Jul 12, DU Ja-09, 07 SN: Collecting duct. RU JAN09; PCT. RU JUL08 1. Functions of the proximal convoluted tubule (PCT): Why maximum reabsorption occurs in PCT? (RU May 16) – (a) It has single layer of cuboidal cells with millions of microvilli which increase surface area for reabsorption. (b)The permeability of the cell membranes to water is very high because of the presence of large numbers of the water channel, aquaporin I, in both the apical and basolateral membrane. (c)The tight junction joining the cells has a very high conductance to small ions. Thus, the permeability of the paracellular pathway to these solutes is high. Thus, the proximal tubule reabsorbs 60 to 70% of the filtrate. It reabsorbs- • Na+ , Cl- & H2O (65%) • HCO3 - (>90%) • Glucose & amino acid (completely) • K+ (98%), PO4 - , Ca2 + , Urea, Uric acid, 2. Functions of the loop of Henle:  The descending limb of the loop of Henle is permeable to water whereas the ascending limb is impermeable. The descending limb causes excretion of water from the tubule. • The ascending limb causes absorption of the Na+ , K+ and Cl- but no water. 3. Function of the distal convoluted tubule (DCT): The distal tubule is a zone of transition. Salt is actively reabsorbed. Water permeability is variable: In the initial segment it is low, in the later segment it varies from low in the absence of antidiuretic hormone, ADH, to high in its presence. Permeability of the paracellular pathway to electrolytes is low. The electrolyte transport mechanisms may be classified as low-rate, high gradient mechanisms. • It reabsorbs most of the ions including Na+ , K+ , Cl- etc. • It is relatively impermeable to water but water reabsorption occurs here with the help of Vasopressin (ADH). • Secretion of K+ and H+ • It is referred to as the diluting segment because it also dilutes the tubular fluid 4. Collecting tubule: Two major cell types are present in the collecting tubule, • the principal cells which reabsorb salt and secrete potassium and • the intercalated cells which secrete protons and bicarbonate. Aldosterone stimulates this transport. Permeability of the paracellular pathway to electrolytes is very low. Permeability to water is low in the absence of ADH, high in its presence. The electrolyte transport mechanisms may be classified as low-rate, high gradient mechanisms.
  9. 9. 6. Renal Physiology 9 CLASSIFICATION OF NEPHRON Classify nephron. RU JAN13, 10 State the difference between the types of nephron. DU may 15 RU May 16, JAN13, 10, SUST Jan 12 According to the location 1. Cortical nephron- 2. Juxtamedullary Nephron Cortical nephron Juxtamedullary Nephron Location Outer cortex Deep in the renal cortex near the medulla Number 85% of the total nephrons 15% of the total nephrons loop of Henle short long Blood supply The entire tubular system is surrounded by an extensive network of peritubular capillaries. Long efferent arterioles extend from the glomeruli down into the medulla than divides into specialized peritubular capillary which concerned with maintenance of hyper osmolar medullary interstitium.
  10. 10. 6. Renal Physiology 10 JUXTAGLOMERULAR APPARATUS What is Juxta glomerular apparatus? CU Nov 17, RU JUL09 What is juxtaglomerular complex? SUST Jan 16 What are the components of juxtaglomerular apparatus. DU Jan 16 Write notes on: Juxta glomerular apparatus. DU Nov 17, RU JAN 14, 13, SUST Jul 11 The macula densa, extraglomerular mesangial cells, and juxtaglomerular cells are collectively known as Juxtaglomerular Apparatus. • It is named for its proximity to the glomerulus. • The juxtaglomerular apparatus is found between the vascular pole of the renal corpuscle and the returning distal convoluted tubule of the same nephron. This location is critical to its function in regulating renal blood flow and glomerular filtration rate. • The juxtaglomerular apparatus regulates the function of each nephron. Components
  11. 11. 6. Renal Physiology 11 The three cellular components of the apparatus are 1. The macula densa, 2. Extraglomerular mesangial cells, and 3. Juxtaglomerular cells (also known as granular cells). Macula Densa Cells At the end of the thick ascending limb, a short segment is present in the distal tubules. These are modified cells- called macula densa. • These are columnar epithelium thickening of the distal tubule. • The macula densa senses sodium chloride concentration in the distal tubule of the kidney and secretes a locally active (paracrine) vasopressor which acts on the adjacent afferent arteriole to decrease glomerular filtration rate (GFR), as part of the tubuloglomerular feedback loop. Juxtaglomerular cells/ Granular Cells Write short note on JG cells. CU Jul 14 These are modified pericytes of glomerular arterioles. The granular cells secrete renin in response to: • Decrease in renal perfusion pressure • Decrease in NaCl absorption in the Macula Densa (often due to a decrease in glomerular filtration rate, or GFR). • Beta1 adrenergic stimulation Extraglomerular Mesangial cells • Mesangial cells are the structural cells in the glomerulus • Under normal conditions serve as anchors for the glomerular capillaries. • The mesangial cells within the glomerulus communicate with mesangial cells outside the glomerulus (extraglomerular mesangial cells), and it is the latter cells that form part of the juxtaglomerular apparatus. These cells form a syncytium and are connected with glomerular mesangial cells via gap junctions. • They contain actin and myosin, allowing them to contract when stimulated by renal sympathetic nerves, which may provide a way for the sympathetic nervous system to modulate the actions of the juxtaglomerular apparatus. Table: Summary of Juxta glomerular apparatus Cells Location Functions Macula Densa Cells Distal tubule Senses sodium chloride concentration Granular Cells Glomerular arterioles Secrete renin Extraglomerular Mesangial cells Outside the glomerulus Contain actin and myosin, allowing them to contract when stimulated by renal sympathetic nerves, which modulate the actions of the juxtaglomerular apparatus. URINE FORMATION AND URINE PATHWAY GLOMERULUS (connecting point with blood supply) ----> filtrate ----> into space of Bowman's capsule ----> proximal convoluted tubule (smaller, brush border of microvilli, cuboidal epithelium) ----> loop of Henle (descending and ascending) ----> distal convoluted tubule (macula densa) (no microvilli, larger lumen) ----> collecting duct ----> minor calyx ----> major calyx (pl. calyces) ----> renal pelvis (sinus outside) ----> ureter ----> bladder ----> urethra ----> urethral orifice.
  12. 12. 6. Renal Physiology 12 . Write short note on: Nephron. RU JAN 15, Special Viva Questions Q: How glomerular basement membrane prevents filtration of plasma proteins? Answer: Because of strong negative electrical charges associated with the proteoglycans. (Guyton, 13th , 336) Q. Explain- mesangial cells play a key role in control of glomerular blood flow. Ans. Mesangial cells can contract . The contraction leads to kinking/obliteration of glomerular capillaries/ Q. Why is nephron called structural unit of the kidney? Ans. Because, the structure of kidney consists mostly of nephrons. Q. Why is nephron called functional unit of the kidney? Ans. The function of each kidney starts from the level of individual nephron. The functions of the kidney are represented as the collective functions of all the nephrons. MCQ Q. Nephrons-(DU-14Ju) a. are constant from birth b. can regenerate c. are of two types d. are the functional unit of kidney e. have three basic functions Ans. a-T, b-F, c-T, d-T, e-T Q. Nephrons-(RU: Ja-06) a. are the functional unit of the kidney b. function as endocrine gland c. have the ability to generate after injury d. are made up a glomerulus and tubules e. are constant from the birth Ans. a-T, b-T, c-F, d-T, e-F Q. The juxtaglomerular apparatus is formed by- (DU- 15M) a. macula densa b. principal cell c. intercalated cell d. lacis cell e. juxtaglomerular cell Ans. a-T, b-F, c-F, d-T, e-T Q. Juxtaglomerular apparatus (RU May 17) (a) is formed by distal tubules near the glomerulus (b) release angiotensinogen (c) control blood flow to the nephron (d) control GFR (e) secrets erythropoietin Ans. a-T, b-F, c-T, d-T, e-F Q. Renin (RU Nov 17) (a) Is secreted by juxtaglomerular cells (b) Is secreted by macula densa cells (c) Control arterial blood pressure (d Acts as an enzyme (e) Directly causes vasoconstriction Ans. a-T, b-F, c-T, d-T, e-F Q. Nephron (DU Nov 16) a. is the functional unit of kidney b. is about I million in each kidney c. Can regenerate d. is constant from birth e. has three basic functions Ans.a)Tb)Tc)Td)Te)T 3. Renal blood flow RENAL BLOOD VESSELS 1. Afferent arteriole: Delivers blood into the glomeruli. 2. Glomerulus: Capillary network that produces filtrate that enters the urinary tubules. 3. Efferent arteriole: Delivers blood from glomeruli to peritubular capillaries. 4. Peritubular capillaries and vasa recta: Deliver blood to renal tubule Glomerular capillary pressure is higher, 60 mm Hg, which helps in glomerular filtration. Peritubular capillary pressure is lower, 13 mm Hg, which helps in tubular reabsorption.
  13. 13. 6. Renal Physiology 13 RENAL BLOOD SUPPLY The renal artery enters the kidney through the hilum and then branches progressively to form the interlobar arteries, arcuate arteries, interlobular arteries (also called radial arteries ) and afferent arterioles, which lead to the glomerular capillaries, where large amounts of fluid and solutes ( except the plasma proteins ) are filtered to begin urine formation. The distal ends of the capillaries of each glomerulus coalesce to form the efferent arteriole, which leads to a second capillary network, the peritubular capillaries, that surrounds the renal tubules. The peritubular capillaries empty into the vessels of the venous system, which run parallel to the arteriolar vessels and progressively form the interlobular vein, arcuate vein, interlobar vein and renal vein which leaves the kidney beside the renal artery and ureter. RENAL BLOOD FLOW (RBF) It is the total volume of blood passes through the both kidney each minute. • 1100ml/minute • Two kidneys constitute only about 0.4 per cent of the total body weight. They receive an extremely high blood flow compared with other organs. (Reference: Guyton, 13th , 325) Renal plasma Flow (RPF) = RBF (1 – hematocrit)= (1–0.45)=1100 mlX0.55=650 ml RENAL FRACTION The percent of cardiac output passes through the both kidney is called renal fraction. Cardiac output in a 70 kg adult = 5000 ml/minute Renal blood flow (RBF) = 1100ml/minute So, Renal fraction =( 1100/5000)X100 = 22% Normal value= 12-30% (Reference: Guyton, 13th , 325)
  14. 14. 6. Renal Physiology 14 PECULIARITIES OF RENAL BLOOD FLOW (RBF) Mention the peculiarities of RBF with their physiological importance. RU May 16, CU Nov 16, May 15, DU Jul 14 Short note: peculiarities of renal circulation. DU May 15, 1. High blood flow - Kidneys have 100 times greater blood flow than other organs and tissues in human organism. Importance: It helps clear waste products very rapidly. 2. Have two capillary bed- • Glomerular capillary- for filtration • Peritubular capillary and vasa recta- for reabsorption and secretion. 3. High pressure capillary bed – Renal arteries are direct branch of abdominal aorta which is a high pressure artery. High pressure results in high hydrostatic pressure. Importance: high hydrostatic pressure fascilates filtration of plasma. 4. The blood distribution in kidneys is uneven - Almost 80 per cent of renal blood perfuses the outer cortical regions. This is why all changes in blood flow will be reflected in alterations of this region. Importance: High blood flow in cortex ensures filtration. Low blood flow in medulla ensures the concentrated urine formation and removal of the more waste products. 5. The arteriovenous difference in blood oxygen content is low in renal blood vessels. 6. Auto regulation of blood flow. Importance: it maintains normal GFR 7. Presence of vasa recta: Hydrostatic pressure is low in this capillary bed because of the high resistance of the afferent and efferent arterioles upstream and circulation is anti-parallel. Osmotic pressure in the vas recta is high because of glomerular filtration. Importance: Low hydrostatic pressure and high osmotic pressure helps in reabsorption of solutes and anti- parallel circulation helps in preserving medullary hyperosmolarity. (Reference: Guyton, 13th , 325 and others) Differentiate between glomerular capillary and peritubular capillary. SUST Jul 13, 11 Glomerular capillary Peritubular capillary For filtration For reabsorption and secretion High hydrostatic pressure Low hydrostatic pressure Located in renal corpuscle Located around renal tubule Exchange occurs through it due to net filtration pressure The majority of exchange through it occurs because of chemical gradients, osmosis and Na+ pumps. AUTO REGULATION Write in short about autoregulation of renal blood flow. DU Jan-13
  15. 15. 6. Renal Physiology 15 State the mechanism of autoregulation of renal blood flow. DU Ju-11 Write down the importance of auto regulation in preventing extreme changes in renal excretion. DU Ja-08 Define auto regulation of renal circulation and mention the factors that are responsible or auto regulation in this bed. DU Ja-06 Definition: Feedback mechanisms intrinsic to the kidneys normally keep the renal blood flow 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. (Guyton) Purpose of auto regulation: 1. To prevent potentially large changes in GFR and renal excretion of water and solutes that would otherwise occur with changes in blood pressure. 2. To allow unwanted substances to pass on into the urine. 3. Reabsorbing the wanted substances. 4. To maintain a constant renal blood flow. (Reference: Guyton) Mechanism: The renal blood flow is auto regulated by the following ways- A. Tubuloglomerular feedback mechanism: TGF occurs between macula densa (MD) cells and cells of the afferent arteriole (juxtaglomerular apparatus). 1. Too little flow of glomerular filtrate into the tubules causes decreased Na+ and Cl- concentration at the macula densa. 2. The decreased ionic concentration causes afferent arteriolar dilatation 3. This allows increases blood flow into the glomerulus, which increases glomerular pressure. 4. The increased glomerular pressure as well as the increased glomerular blood flow increases the glomerular filtration rate (GFR) back towards the required level. 5. The increased pressure then causes back toward normal. The opposite happens when delivery and transport at the MD are increased. B. Myogenic mechanism: Myogenic autoregulation depends on stretch activated ion channels in vascular smooth muscle. Arterial pressure rises > stretches the wall of the arteriole > secondary contraction of arteriole > decreases renal blood flow (back towards normal) Conversely, when pressure fall, an opposite myogenic response allows the artery to dilate and therefore increases renal blood flow. When both these mechanisms function together the glomerular filtration rate increases only a few percent even through the arterial pressure changes between the limits of 75 and 160 mm/Hg. Give an account of renal circulation. RU May 16 Viva Q Q: What is the purpose of high blood flow blood in kidney? Answer: the high blood flow to the kidneys greatly exceeds this need. 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.(Reference: Guyton) Q: Marked increases in renal blood flow and GFR occur with large increases in blood glucose levels in uncontrolled diabetes mellitus. Why?
  16. 16. 6. Renal Physiology 16 Because glucose (like some of the amino acids) is also reabsorbed along with sodium in the proximal tubule, increased glucose delivery to the tubules causes them to reabsorb excess sodium along with glucose. This, in turn, decreases delivery of sodium chloride to the macula densa, activating a tubuloglomerular feedback–mediated dilation of the afferent arterioles and subsequent increases in renal blood flow and GFR. Explain: Capillary BP in the glomeruli is high. This because efferent arteriole from the glomerulus is narrow while the afferent arteriole to the glomerulus has a wider diameter (p. 443). The high glomerular BP aids in glomerular filtration. MCQ Q. Renal blood flow is incrased due to-(DU-14Ja) a. intake of high protein diet b. hyperglycaemia c. aging d. hypoglycemia e. increase blood glucocorticoid level. Ans. a-T, b-T, c-T, d-F, e-F Q. Renal blood flow-(DU-13J) a. is 10% of cardiac output b. is auto regulated c. when decreases cuases decreased GFR d. is measured by PAH clearance test e. 1.2 to 1.31/min Ans. a-F, b-T, c-T, d-F, e-F Q. Factors that increase the renal blood flow are- (DU-10Ju) a. norepinephrine (F) b. old age (F) c. hyperglycemia (F) d. glucocorticoids (F) e. prostaglandin E2 (T) Q. Approximate pressure in renal circulation- (RU: Ja- 05) a. renal arteray: 100 mm of Hg. (T) b. afferent arteriole 85 mm of Hg.(?) c. glomerular capillaries: 10 mm of Hg. (F) d. efferent arteriole: 60mm of Hg (?) e. renal vein: 4 mm of Hg. (T) Q. Autoregulation of renal blood flow: (CU:Ja-07) a. occurs at pressure of 90 to 220 mm of Hg b. is present in denervated kidney c. is due to contraction of afferent arteriole d. is due to constriction of efferent arteriole e. is increased with arterial pressure Ans. a-T, b-T, c-T, d-T, e-T Q. Peritubular capillaries (DU May 16) a. end in the venous system b. have hydrostatic pressure about 32 mm Hg c. arise from afferent arterioles d. surround renal tubules e. permit filtration of fluid Ans. a-T, b-F, c-F, d-T, e-F Q. RBF is increased when (DU Nov 17) a. increased intake of high protein diet b. hyperglycaemia occurs c. glucocorticoid secretion is increased d. renal artery constricts e. aging occurs Ans. a-F, b-T, c-F, d-F, e-T Q. Renal blood flow: (CU May-16) a) Rises during emotional stress b) Rises with increased circulating catecholamines c) Falls gradually from the inner medulla to the outer cortex d) Falls when arterial pressure fall; 10% below normal e) Falls after moderate hemorrhage Ans: a) T b) F c)F d) T d) T 4. Glomerular Filtration Rate (GFR) DEFINITION Define GFR. DU May 17, 15, Jan 14, Jul 15, Ja-11, 10, Ju-11, CU Nov 17, 16, Jul 15, Jan 15, 14, RU MAY 18, 17, NOV 15, JAN 13, 11, 10, 09, SUST Jan 16, Jul 12 The quantity of glomerular filtrate formed in each minute by all the nephrons of both kidneys is called Glomerular Filtration Rate (GFR). NORMAL GFR • The GFR in an average-sized normal man is approximately 125 ml/min (>7.5 L/h, or 180 L/d). • Its magnitude correlates fairly well with surface area, but values in women are 10% lower than those in men even after correction for surface area.
  17. 17. 6. Renal Physiology 17 • Normal urine volume is about 1 L/d. Thus, 99% or more of the filtrate is normally reabsorbed. At the rate of 125 mL/min, the kidneys filter in 1 day an amount of fluid equal to 4 times the total body water, 15 times the ECF volume, and 60 times the plasma volume (Ganong) FILTRATION PRESSURE Calculate net filtration pressure. CU May 16, DU Nov 17, 16, 15, Jan 14, Jul 15 RU JUL 14, SUST Jul 12, 11 Write down the mechanism of filtration in the glomerular membrane. CU May 15, Jul 15, DU Jan-13 How is the effective filtration pressure created? DU Jan-12, 11 List the pressure involve for filtration through filtrating membrane. RU JAN11,09 The filtration pressure is the net pressure forcing fluid through the glomerular membrane. It is about 10 mm Hg. Factors favoring filtration (mm of Hg) Factors against filtration (mm of Hg) Glomerular hydrostatic pressure 60 Bowman’s capsule hydrostatic pressure 18 Bowman’s capsule colloid osmotic pressure 0 Glomerular capillary colloidal osmotic pressure 32 Total 60 Total 50 So net filtration pressure = (60-50) mm of Hg = +10 mm of mg. Net filtration pressure +10 mm of mg causes the filtration of glomerular filtrate. (Guyton, 13th , 337) THE FILTRATION COEFFICIENT The GFR can be expressed as the following formula: GFR = Kf x net filtration pressure Kf = the filtration coefficient It is defined as the GFR of both kidneys per mm Hg of filtration pressure. Kf can furthermore be expressed by the following formula Kf = membrane permeability x filtration area
  18. 18. 6. Renal Physiology 18 The GFR is practically proportional to metabolic body mass. Therefore the bigger the animal the greater the GFR. What is the normal value of filtration coefficient for glomerular membrane? RU NOV 15 Normal Kf for glomerular membrane is 12.5. So, GFR = Kf x net filtration pressure = 12.5X10= 125 ml/minute. (Guyton, 13th , 337) FACTORS CONTROLLING GFR Explain the factors affecting GFR. SUST Jan 16 Mention the factors affecting GFR. CU Jul 15, 14, Jan15, 14, DU Nov 15, Jan 14,11, 10, Jul 12,15 RU MAY 18, 17, JAN 15, 14 State the major factors affecting/control GFR. RU NOV 15, JAN 13, 11 10, 09 Primary factors: 1. Glomerular hydrostatic pressure: It promotes filtration through glomerular membrane. 2. Colloidal osmotic pressure of plasma: It opposes filtration. 3. Bowman’s capsular pressure: It opposes filtration. Secondary Factors Factors that cause ↑ glomerular pressure ↑ GFR. On the other hand the factors that causes ↑ bowman’s capsular pressure or colloidal osmotic pressure causes ↓GFR. Thus following factors can secondarily affects GFR : 1. Renal blood flows: ↑Renal blood flow→ ↑ Glomerular hydrostatic pressure → ↑GFR. But when plasma filters through it, it causes accumulation of plasma protein thus ↓GFR later. 2. Afferent arteriolar constriction: This causes ↓blood flow into glomerular capillary→ ↓glomerular hydrostatic pressure → ↓GFR. 3. Efferent arteriolar constriction: This causes↓ blood flow into glomerular capillary → ↑ glomerular hydrostatic pressure → ↑ GFR. But when constriction is prolonged, plasma will remain for a long period → ↑ colloidal osmotic pressure which paradoxically causes ↓GFR. 4. Changes in hydrostatic pressure in Bowman's capsule: increased pressure will decrease GFR. This pressure may increased in- • Ureteral obstruction • Edema of kidney inside tight renal capsule 5. Changes in concentration of plasma proteins: decreased concentration will increase GFR. concentration of plasma proteins decreased in dehydration, hypoproteinemia, etc (minor factors) 6. Sympathetic stimulation: Arterial constriction > ↓ GFR. 7. Change in the total area of capillary bed: ↓Total glomerular capillary bed of glomerular membrane → ↓GFR. 8. Permeability of capillary membrane: Directly proportional to GFR change. Increase permeability increase GFR and Decreased permeability decrease GFR. 9. Contraction of mesangial cells – decrease GFR 10. Tubo glomerular feedback 11. Protein meal- increase GFR after 1-2 hour of intake. 12. Blood Glucose – increase blood glucose increase GFR. 13. Hormones/Autacoids: o increase a. Endothelial-derived nitric oxide b. Prostaglandin’s (PG) c. Bradykinins d. Atrial Natriuretic peptide (ANP) e. brain Natriuretic peptide (BNP)
  19. 19. 6. Renal Physiology 19 o Decrease a. Angiotensin II b. Epinephrine , Nor epinephrine c. Endothelin (Guyton, 13th , South Asian edition, 474) Substances filtered through the glomerular membrane Filtered Not filtered Low molecular weight substances (including smaller peptides) Most plasma proteins ie. Albumins & Globulins. water Plasma calcium and fatty acids (Guyton, 13th , 335) GLOMERULAR FILTRATE It is the fluid that filters through the glomerular membrane into the Bowman’s capsule. Daily amount of Glomerular filtrate: Normally glomerular filtration rate is 125 ml/min or 180 liter/day. Composition (character) of glomerular filtrate/Differences with blood What are the differences between blood and glomerular filtrate? RU JUL 14 Its composition is as the fluid that filters from the arterial ends of the capillaries into the interstitial fluid. 1. It is isotonic to plasma. Osmolarity is 280-300 mosm/L 2. The electrolyte and other solute composition is similar to that of plasma, But- a. concentration of anion is 5% greater to that of plasma b. concentration of cation is 5% lesser to that of plasma c. Almost one half of the plasma calcium and most of the fatty acids are bound to proteins, and these bound proteins are not filtered through the glomerular capillaries. 3. Devoid of cellular elements including RBC 4. It is essentially protein free, may contains about 0.03 mg % proteins only. 5. pH is 7.40 6. Specific gravity is 1.009-1.010 So, glomerular filtrate is almost same as the plasma except that it has no significant amount of protein. (Reference: Guyton and Ganong) ULTRAFILTRATION ULTRAFILTRATION Production of filtrate from the blood is called ultrafiltration. Blood enters the capillaries of the glomerulus, and water/solutes are forced into Bowman’s capsule to create the filtrate. Mediated by hydrostatic pressure and colloid osmotic pressure. Explain- Glomerular filtrate is called an ultrafiltrate. An ultrafiltrate is filtrate minus the proteins. Glomerular filtrate contains only negligible amount of protein, so it is an ultrafiltrate MEASURING GFR How can you measure GFR? RU MAY 18, 17, CU Jul 14, Jan 15, 14, DU Ju-10
  20. 20. 6. Renal Physiology 20 • The glomerular filtration rate (GFR) can be measured in intact experimental animals and humans by measuring the excretion and plasma level of a substance that is freely filtered through the glomeruli and neither secreted nor reabsorbed by the tubules. • If o the substance is X o concentration of X in urine UX o the urine flow per unit of time V o the arterial plasma level of X is PX GFR will be = (UX/PX) X V This value is called the clearance of X (CX). (Ganong) Inulin, a polymer of fructose with a molecular weight of 5200 that is found in dahlia tubers, meets these criteria. Plasma and urinary inulin concentrations are determined and the clearance calculated as follows. Clearance of creatinine (CCr) is used to determine the GFR. (Ganong) Explain why is inulin clearance equal to GFR? RU JUL12 Why inulin is used for measuring GFR. DU Jan 14, SUST Jul 13 Clearance of creatinine (CCr) is used to determine the GFR, as it is freely filtered through the glomeruli and neither secreted nor reabsorbed by the tubules. Criteria of Substances Used to Measure GFR List the characteristics of a substance suitable for measuring GFR. RU JAN10 Substance (such as inulin) should 1. be freely filtered 2. neither reabsorbed nor secreted in the tubules 3. Should be nontoxic and 4. Not metabolized by the body. 5. Not bound to plasma proteins 6. Not stored in the kidney 7. Have no any effect on filtration rate (Ganong) Explain the differences in the concentration of proteins, glucose and urea between blood plasma, glomerular filtrate and urine. Molecule Concentration (mg/100 ml) Blood plasma Glomerular filtrate Urine Proteins >700 0 0 Glucose >90 >90 0 Urea 30 30 >800
  21. 21. 6. Renal Physiology 21 1. Proteins are too large to fit through basement membrane, so don’t become parts of filtrate or urine. Also negative charge of glomerular membrane cause repulsion of protein. 2. Glucose becomes part of filtrate but active transport takes 100% of glucose back into capillary bed. 3. Urea is not toxic in low levels in blood plasma. High concentration of urea in urine is due to reabsorption of water. FILTRATION FRACTION Define filtration fraction. DU Nov 17, 16, Ja-11, 10 If plasma flow through both kidneys is 650 ml/ min, GFR is 125 ml/min, What will be the filtration fraction? DU Jan 15, Ju-12, Ju- 09 It is the portion of plasma that filters through the renal glomerular membranes. Glomerular Filtration Rate Filtration Fraction = X100 Renal Plasma Flow 125 ml/minute = X100 650 ml/minute = 19.23% (Guyton, 13th , 335) AUTOREGULATION OF GFR Briefly describe the autoregulation of GFR. CU Nov 16 How GFR is autoregulated by tubuloglomerular feedback. CU May 16 How GFR is auto regulated? DU May17 State tubuloglomerular feed back mechanism for controlling GFR. DU May 16, CU May 15, Jul 15, RU JUL09, 08 What is autoregulation? - Feedback mechanisms intrinsic to the kidneys normally keep the renal blood flow and GFR relatively constant, despite marked changes in the arterial blood pressure. This relative constancy of GFR and renal blood flow is called autoregulation. Importance- 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. Mechanism- 1. Sodium changes in macula densa causes control of renal arteriolar resistance and renin release. When GFR is decreased, the flow of fluid in the loop of Henle is decreased. Thus the reabsorption of sodium chloride in the ascending limb is increased and the concentration of sodium
  22. 22. 6. Renal Physiology 22 chloride is decreased at the macula densa cells. This decreased sodium in macula densa is associated with tubuloglomerular feedback preventing much decrease in GFR. 2. Tubuloglomerular feedback includes a) afferent arteriolar feedback mechanism and b) efferent arteriolar feedback mechanism A. Afferent arteriolar feedback mechanism: Decreased concentration of NaCl at the macula densa cell causes decreased resistance to blood flow in afferent arteriole ↓ increased glomerular hydrostatic pressure ↓ Increased GFR towards normal. B. Efferent arteriolar feedback mechanism: Decreased concentration of sodium chloride at the macula densa cells causes increased renin release from JG cells of the efferent and afferent arteriole. Consequently it causes increased formation of angiotensin I and angiotensin II. Angiotensin II constricts the efferent arteriole. As a result, the glomerular capillary hydrostatic pressure is increased which causes increased GFR towards normal. (Reference: Guyton, 13th , 342-345) Write short note on GFR. SUST Jul 13 Special Viva Questions Q. Explain the mechanism of proteinuria The negative charges of the basement membrane and the podocytes provide an important means for restricting large negatively charged molecules, including the plasma proteins. In certain kidney diseases, the negative charges on the basement membrane are lost even before there are noticeable changes in kidney histology, a condition called minimal change nephropathy. As a result of this loss of negative charges on the basement membranes, some of the lower molecular weight proteins, specially albumin, are filtered and appear in the urine. This condition is called proteinuria or albuminuria. Q. Explain the presence of glucose in the urine of untreated diabetic patients. • untreated diabetic patients have elevated blood glucose levels • after ultrafiltration, the glomerular filtrate therefore also has elevated glucose levels • reabsorption in the convoluted tubules cannot move enough glucose back to the blood plasma • therefore, the urine contains glucose MCQ Q. GFR is increased when-(SU-14Ju) a. plasma oncotic pressure is increased b. glomerular capillary hydrostatic pressure is increased c. afferent arteriolar constriction occurs d. renal blood flow in increased e. when blood pressure is decreased Ans. a-F, b-T, c-T, d-T, e-F Q. GFR increases in increased-(DU-14J) a. plasma oncotic pressure b. Bowman's capsular hydrostatic pressure c. tubular hydrostatic pressure d. renal blood flow e. glomerular capillary hydrostatic pressure Ans. a-F, b-F, c--F, d-T, e-T Q. The determinants of GFR are-(DU-14J) a. Kf b. filtration fraction c. net filtration d. TmG e. clearance of water Ans. a-T, b-T- c-F, e-F Q. GFR is increased when-(DU-12Ju) a. plasma oncotic pressure increased (F) b. glomerular pressure in increased (T) c. renal blood flow is increased (T) d. plasma protein is decreased (T) e. Bowman's capsule pressure is increased (F) Q. GFR is reduced deu to-(DU-12J) a. elevated blood pressure (F)
  23. 23. 6. Renal Physiology 23 b. constriction of afferent arterioles (T) c. decrease in Bowman's capsular hydrostatic pressure (F) d. increase in plasma proteins (F) e. dilation of efferent arteriols (T) Q. GFR is reduced due to- (DU-10Ju) a. elevated blood pressure (F) b. constriction of afferent arterioles (T) c. decrease in Bowman's capsular hydrostatic pressure (F) d. increase in plasma proteins in blood (F) e. dilation of efferent arterioles (T) Q. GFR (RU: Ja06) a. increases when oncotic pressure in increased. b. is decreased in efferent arteriolar constriction c. decreases markedly when perfusion pressure below 80mm Hg. d. is increased in ureteric obstruction e. is relatively constant when perfusion pressure changes from 90-220 mm Hg. Ans. a-F, b-F, c-T, d-F, e-T Q. GFR increase in : (RU: Ju-07) a. Urethral obstruction b. Afferent arteriole constriction c. Increased hydrostatic pressure in glomeruli d. Mild constriction of efferent arteriole e. Hypoproteinemia Ans. a-F, b-F, c-T, d-F, e-T Q. GRF is increased when: (CU: Ja-07) a. glomerular capillary hydrostatic pressure is increased b. plasma oncotic pressure is increased c. Bowman's capsule pressure is increased d. Renal blood flow is increased e. Glomerular capillary filtration coefficient is decreased Ans. a-T, b-F, c-F, d-T, e-F Q. GFR is increased when (RU May 16 a. afferent arteriolar resistance (RA) is increased b. filtration coefficient(kf) is increased c. there is urinary tract obstruction d. angiotensin II effect in increased e. net filtration pressure is increased Ans. (a) T (b) T (c) F (d) F (e) T Q. GFR increase due to a. increase Bowman’s capsular hydrostatic pressure b. increase in colloidal osmotic pressure in glomerular capillary c. increase in Bowman’s capsular colloidal osmotic pressure d. decrease in Bowman’s capsular hydrostatic pressure e. rise in glomerular capillary hydrostatic pressure Ans. (a) F (b) F (c) T (d) T (e) T Q. GFR is increased when (DU Nov 16) a. blood pressures decreased b. glomerular hydrostatic pressure is increased c. plasma oncotic pressure is increased d. renal blood flow increased e. Bowman’s capsular hydrostatic pressure is increased Ans. a)F b)T c)F d)T e)F Q. GFR is: (CU May-16) a. relatively constant b. is about 20% of the renal plasma flow c. increased by angiotensin II stimulation d. altered by mesangial cells excitation e. is 125 L/min Ans: a) T b) T c)F d) F d) T e)T Q. GFR is increased when: CU/Jan 09 (a) Glomerular capillary hydrostatic pressure is increased (b) Plasma oncotic pressure is increased (c) Bowman’s capsule pressure is increased (d) Renal blood flow is increased (e) Glomerular capillary filtration coefficient is decreased Ans: (a)T (b)F (c)F (d)T (e)F 5. Tubular Reabsorption and Secretion Reabsorption (movement from tubular fluid to peritubular blood) and secretion (movement from peritubular blood to tubular fluid) refer to direction of movement of solutes and water across the renal tubular epithelium. TERMINOLOGY • The luminal cell membranes are those that face the tubular lumen (“urine” side) • The basolateral cell membranes are those are in contact with the lateral intercellular spaces and peritubular interstitium (“blood” side) • The term transcellular refers to movement of solutes and water through cells • The term paracellular refers to movement of solutes and water between cells • Epithelial cell junctions can be “leaky” (proximal tubule) or “tight” (distal convoluted tubule, collecting duct)
  24. 24. 6. Renal Physiology 24 • • Figure: Locations for filtration, reabsorption, secretion & excretion • • Diagramatic representation of tubular epithelium (Widmaier E. et al, 2008) ROUTES OF TRANSPORT ACROSS PROXIMAL TUBULAR EPITHELIUM 1. Transcellular • 99% of surface area • 90-95% of water transfer • Passive or active transport • All active transport occurs by this route 2. Paracellular • 1% of surface area • 5-10% of water transfer • Passive diffusion or solvent drag only
  25. 25. 6. Renal Physiology 25 • Requires favorable electrochemical gradient • Passive diffusion of ions and large non-polar solutes TYPES OF TRANSPORT PROCESSES 1. Primary Active Transport: ATP-driven pump in basolateral membrane pumps Na+ out/K+ in -sets up electrochemical gradient to cause other solutes and water to move out of lumen. Examples • Na+ -K+ ATPase o Example of active transport: Na+ -K+ pump: o Most of the filtered Na+ is reabsorbed by the Na pump in the proximal tubule (~65%) o Na+ pumping in the ascending loop of Henle sets of osmotic gradients that are used to regulate water (~25%) o Fine tuning of Na+ is done by Na+ pumps in the distal tubule and collecting duct, which are controlled by the hormone, aldosterone • H+ ATPase • H+ -K+ ATPase • Ca+2 ATPase 2. Secondary Active Transport: other solutes move by co-transport or symport with Na+ ions -energy for this transport comes from the electrochemical gradient Examples • Glucose, amino acids, or phosphate with sodium in luminal membranes of proximal tubules • Sodium and hydrogen ions in luminal membranes of proximal tubules 3. Osmosis and Passive Diffusion: passive movement of substances down electrochemical gradient -Osmosis: water follows the salt and other solutes out of lumen -as water leaves> the concentration ↑ for other solutes in filtrate > ↑ their diffusion out -Passive Diffusion: works for urea, some ions (Cl- , K+ ) 4. Facilitated Diffusion: carriers in basolateral membrane passively move some solutes into IF -used for glucose and some other organic solutes -no cotransport with Na+ is involved with this process • Glucose, amino acids: Basolateral membranes of proximal tubules • Sodium: luminal membranes of proximal tubules 5. Pinocytosis • Endocytosis: Filtered proteins absorbed to sites on luminal membranes that are internalized to form endosomes. Fusion with lysosomes forms endolysosomes in which digestion of proteins occurs • Hydrolysis of filtered proteins to constituent amino acids by enzymes in brush border of proximal tubular cell. 6. Solvent drag: A solvent such as water moving across an epithelium by osmosis can drag dissolved solutes with it 7. ultrafiltration (bulk flow) SUBSTANCES REABSORBED AND SECRETED IN THE KIDNEY List the substances completely reabsorbed in PCT. RU NOV 17, JUL14, JAN13, 10, DU Nov 17, 15, Ju-12,15 Name the substances that are reabsorbed & secreted from PCT & DCT. CU May 17 Name the substances that are reabsorbed in proximal convoluted.tubule. RU JUL 15 List the sites of Na+ reabsorption in the renal tubules. RU JUL13 List the substances that are reabsorbed in the different parts of renal tubules. DU Jan-13, Jul 14 State Mechanism of Na+ reabsorption in the different part of the renal tubular system. DU Ju-09
  26. 26. 6. Renal Physiology 26 Table: Substances reabsorbed and secreted in the kidney Parts of Nephron Reabsorption Secretion PCT- “workhorse’ of the nephron. • Actively reabsorbed: Glucose, amino acid, vitamin, acetoacetate. Ions: Na+ , K+ , HCO3 - , Ca++ , SO4 - • Actively and completely: Glucose, amino acids, vitamins, proteins. • Passively reabsorbed: Water, Cl- Secretion: K+ , H+ creatinine, drugs thin descending segment* • Highly permeable to water and • Moderately permeable to most solutes, including urea and sodium. thin ascending segment* Same as thin descending limb except less absorption of water thick ascending segment* • Impermeable to urea & water. • Active reabsorption of sodium, chloride and potassium. • There is also significant paracellular reabsorption of cations, such as Mg++ , Ca++ , Na+, and K+ , Distal convoluted tubule: Diluting segment: • Reabsorbs most of the ions, including sodium, potassium, and chloride, • But is virtually impermeable to water and urea. For this reason, it is referred to as the diluting segment . Late distal tubule and cortical collecting tubule The second half of the distal tubule and the subsequent cortical collecting tubule have similar functional characteristics. • impermeable to urea, • K+ (controlled by Aldosterone). • H+
  27. 27. 6. Renal Physiology 27 • reabsorb sodium ions (controlled by Aldosterone). • Water – Reabsorption in presence of ADH. Medullary Collecting Duct • Water (controlled by ADH) • urea H+ , NH3 *The loop of Henle consists of three functionally distinct segments: the thin descending segment, the thin ascending segment, and the thick ascending segment (Reference: Guyton) PRIMARY FUNCTIONS OF TUBULAR RE-ABSORPTION As the filtered liquid, known as filtrate, flows through nephrons, useful materials are returned to the blood by the process of re-absorption PRIMARY FUNCTIONS OF TUBULAR SECRETION a. Clear body of certain substances such as drugs or wastes (urea, creatinine, NH4 + . b. removing excess K+ from blood c. regulating pH (H+ ion removal) Table: Amount of different substances reabsorbed into the blood as the filtrate passes down the nephron Substance % Reabsorbed Water 99.4% Na+ 99.4% K+ 93.3% HCO3 - 100% Glucose 100% Urea 53% Inulin 0% (Reference: Ganong) MECHANISM OF TRANSPORT OF Na+ State the mechanism of reabsorption of Na+ from renal tubules. CU Jan 16, nov 15,RU NOV 17, 16, JUL15, 14, 13, JAN12, SUST Jan 12 State the Na+ reabsorption from thick segment of LH & distal convoluted tubule. RU JUL08 State the reabsorption of Na+ from thick segment of loop Henle. RU JUL08 Path of transport Mechanism From Tubular lumen into tubular epithelial • Passive diffusion • Secondary active transport (e.g. Na+ -glucose co-transport or Na+ -H+
  28. 28. 6. Renal Physiology 28 cells counter-transport) by electrochemical gradient (-70 mv) established by Na+ -K+ ATPase pump on the basolateral side of the membrane. From tubular epithelial cells into interstitium Na+ -K+ ATPase pump From interstitium into blood Ultrafiltration MECHANISM OF TRANSPORT OF GLUCOSE: State the mechanism of glucose reabsorption from PCT. DU Nov 17, SUST Jan 16, RU JUL 15, JAN 14, 13, 10 How is glucose reabsorbed in renal tubules? CU Jan 16, Nov 15, DU Nov 15, Jan-13 State the mechanism of reabsorption of glucose from nephron. RU MAY 17, JAN 11 Path of transport Mechanism From Tubular lumen into tubular epithelial cells By Secondary active transport (Na+ -glucose co-transport): • The carrier in the cell membrane has two binding sites- one for Na+ and another for glucose. • When Na+ and glucose binds with the respective sites, a conformational change of the carrier protein takes palace. • The carrier moves from tubular lumen to the interior of tubular epithelial cell with the help of energy derived from the concentration gradient of Na+ between outside and inside. • Then inside the epithelial cell, the Na+ and the glucose split from the carrier. From tubular epithelial cells into interstitium Facilitated diffusion From interstitium into blood Ultrafiltration MECHANISM OF REABSORPTION OF HCO3 - FROM RENAL TUBULE Illustrate the mechanism of reabsorption of bicarbonate ions by the-renal tubules. DU Jul 10, 14 Path of transport Mechanism
  29. 29. 6. Renal Physiology 29 From Tubular lumen into tubular epithelial cells The renal tubules are not permeable to HCO3 + ion because it is a large ion and also ECF is electrically negative charged. HCO3 is reabsorbed as CO2 by the following ways: In the kidney tubules, HCO3 + reacts with H+ secreted in the tubular fluid to from H2CO3 This H2CO3 is then dissociated to from CO2 & H2O. From tubular epithelial cells into interstitium The tubular epithelial membrane is highly permeable to CO2. This causes diffusion of CO2 from tubular fluid into extracellular fluid through tubular epithelium. Figure: Mechanism of transport of HCO3 + RENAL CONTROL OF K+ LEVELS • 10-15% constantly lost in urine • Most reabsorption occurs in proximal tubule • Regulation - changing amount secreted into urine in the collecting tubules o Low K+ ----> less secretion (intercalated cells in collecting tube can reabsorb more) o High K+ -----> more secretion Factors Controlling K+ Secretion  Tubule cell intracellular K+ level : when low, secrete less; when high, secrete more  aldosterone : help K+ secretion, Na+ reabsorbtion a. increase aldosterone -> more K+ secretion b. decrease aldosterone -> less K+ secretion  pH : K+ and H+ compete for antiport with Na+ a. lower pH (high H+ ) -> less K+ secretion b. higher pH (low H+ ) -> more K+ secretion POTASSIUM REABSORPTION BY THE KIDNEY
  30. 30. 6. Renal Physiology 30 Site Amount Mechanism Proximal Tubule About 65% There are no specific K-transporter, reabsorption is managed with the absorption of water (solvent drag). Loop Of Henle 25–30% Potassium is actively co transported along with sodium and chloride. Distal Nephron 5–15% controlled by aldosterone (Depending on the metabolism there are possibilities of potassium reabsorption or excretion) RENAL CALCIUM REABSORPTION 60% of the filtered calcium is reabsorbed in the proximal tubule with the paracellular absorption of water (solvent drag). Additionally, there are active transport mechanisms. RENAL PHOSPHATE REABSORPTION Phosphate is completely filtered, 80–90% of the phosphate are reabsorbed in the proximal tubule. With high phosphate concentrations in serum, a saturation of the phosphate reabsorption is reached and phosphate is excreted till the normalization of the phosphate concentration. An increased phosphate concentration is the stimulus for the parathyroid hormone release and leads to phosphate excretion, calcium phosphate deposition into the bone and lowers the serum calcium. REABSORPTION OF WATER Normally about 99.3% of the filtered load of water is reabsorbed in the renal tubular system with excretion of averages 1 ml/minute urine. Table: Reabsorption at water at different pats of the tubules: Name the sites of water re-absorption of water in renal tubule. RU MAY 18, 16, JUL 14 Site Amount of filtered water reabsorbed Mechanism PCT 65-70% Osmosis Descending limb of LH 15% Osmosis Ascending limb of LH 0% DCT 5-10% Osmosis. Reabsorption depends on the presence of circulating ADH.
  31. 31. 6. Renal Physiology 31 Collecting system 14.3% (2% in the absence of ADH) Osmosis. Reabsorption depends on the presence of circulating ADH. (Reference: Ganong) Aquaporins Rapid diffusion of water across cell membranes depends on the presence of water channels, integral membrane proteins called aquaporins. To date, 13 aquaporins have been cloned; however, only 4 aquaporins (aquaporin-1, aquaporin-2, aquaporin- 3, and aquaporin-4) play a key role in the kidney. (Ganong, 25th ) Types of water reabsorption How is water reabsorbed in renal tubules? DU Ju-12 1. Obligatory water reabsorption: When the water reabsorption occurs as result of osmotic force generated by solute reabsorption, the reabsorption is called Obligatory water reabsorption. Mechanism: – Increased sodium reabsorption  increased water reabsorption 2. Facultative reabsorption of water: When water reabsorption occurs under the influence of Anti- diuretic hormone (ADH), it is called Facultative reabsorption of water. (Ref. Guyton & Hall) Mechanism: Osmoreceptors in hypothalamus sense increased osmolarity → posterior pituitary releases ADH → activates the enzyme adenyl cyclase in the basolateral membrane → adenyl cyclase causes formation of cyclase in the membrane → cyclase then causes formation of cyclic adenosine monophosphate (cyclic AMP) in the cell cytoplasm → cyclic AMP then diffuses to the luminal membrane of the cells → phosphorylation of water channels (aquaporin-2) → more water is reabsorbed. (Ref. Guyton & Ganong) Difference between obligatory and facultative water reabsorption Obligatory Facultative 1. It takes place in the PCT. 2. It occurs along with the reabsorption of (electrolyte) Na+ . 3. Rate of reabsorption is proportional to GF of the iso-osmotic condition. 1. It takes place in the DCT and CT. 2. It occurs under the influence of ADH. 3. Rate of reabsorption is proportional to the ADH secretion. Non-reabsorbed Substances Urea, creatinine, uric acid - most is not reabsorbed because of the following reasons  no carrier molecules for active transport  not lipid-soluble  too large (as with most proteins) HORMONAL REGULATION OF TUBULAR REABSORPTION AND SECRETION Name the hormones acting on kidney with functions of any 3 of them. DU Jan 14. CU Jan14 Name the hormones acting on kidney. DU Nov 17, 16, Jan 17, CU Jan 16, Nov 15, RU MAY 15, SUST Jan 12
  32. 32. 6. Renal Physiology 32 Name the hormones that regulate tubular reabsorption. DU Ju-12 Make a list of 05 hormones that regulate tubular reabsorption. DU Ju-07 1. Aldosterone  Site of Action: Collecting tubule and duct  Effects: ↑ NaCl, H2O reabsorption, ↓K+ secretion Release stimulated by: • Decreased blood volume (via Angiotensin II) • Increased plasma K+ 2. Renin-Angiotensin System Site of Action: Proximal tubule, thick ascending loop of Henle/distal tubule, collecting tubule Effects: ↑ NaCl, H2O reabsorption, ↓K+ secretion Release stimulated by: Decreased blood volume (via renin) Mechanism: • Blood pressure decrease results in renin release by JG cells • Renin converts angiotensin into Angiotensin I • Angiotensin I converted to active form Angiotensin II which: 1. Decreases glomerular filtration rate 2. Enhances reabsorption of Na+ , Cl- , and water 3. Stimulates release of aldosterone to reabsorb more Na+ , Cl- , and water 3. Antidiuretic Hormone / Vasopressin Site of Action: Distal tubule/collecting tubule and duct Effects: ↑ facultative water reabsorption by principal cells of distal tubule/collecting tubule and duct. It has negative feedback role. Release stimulated by: decreased • Blood water concentration in blood • Blood volume 4. Atrial Natriuretic Peptide (ANP) Site of Action: Distal tubule/collecting tubule and duct Effects: 1. Inhibits electrolyte and water reabsorption 2. Suppresses secretion of aldosterone and ADH Released from: heart Release stimulated by: increased atrial pressure due to large increase in blood volume Mechanism: Stretch of atrial wall → ANP secretion → reduces Na+ and water reabsorption in PCT and CD and inhibits secretion of ADH and aldosterone 5. Parathyroid hormone Site of Action: Proximal tubule, thick ascending loop of Henle/distal tubule. Effects: a. Increase tubular reabsorption of Ca++ b. Increase tubular excretion of PO4 ++ . Release stimulated by: decreased plasma Ca++ 6. Calcitonin. Effects: a. increase excretion of Ca++ & PO4 ++ . b. Inhibit the synthesis of calcitriole RENAL THRESHOLD
  33. 33. 6. Renal Physiology 33 What do you mean by renal threshold of glucose? Du May 15, CU Nov 17,16, Jan 15 Explain the renal threshold of glucose is 180 mg/dl. CU Jan 15, Define the terms renal threshold. RU MAY 17, DU Ju-11 Short notes: Renal threshold DU Ju-11, Ja-07 It is the plasma concentration of a substance at or below which the substance will not appear in urine, but above which it will appear in urine gradually. When the renal threshold of a substance is exceeded, reabsorption of the substance is incomplete; consequently, part of the substance remains in the urine. Example: Renal threshold for glucose is 180 mg/dl. This means when plasma level of glucose is 180 mg/dl or below 1 80 mg/dl, glucose will not appear in the urine; but whenever plasma glucose level exceeds 180 mg/dl, glucose will appear in the urine. (Ref Guyton) The most common reason for the glucose renal threshold ever being exceeded is diabetes. TRANSPORT MAXIMUM (Tm) Explain transport maximum of glucose is 320 mg/min? CU Nov 17, Jan 15, DU May 15 What do you mean by transport maximum? RU NOV 16, DU Ju-13, What do you mean by TmG? CU Nov 16 Short notes: TmG. SUST Jan 16, DU Ju-08 It is the maximum rate of secretion or reabsorption of a substance by the renal tubules. In this maximum limit, increases in concentration do not result in an increase in movement of a substance across a membrane. For example, Tm of glucose =375 mg/ minute. It means that maximum 375 mg glucose can be reabsorbed through the tubule in each minute. If the tubular load of glucose is above this value, then excess glucose is excreted out through the urine. Cause: This limit is due to saturation of the specific transport systems involved when the amount of solute delivered to the tubule (referred to as tubular load) exceeds the capacity of the carrier proteins and specific enzymes involved in the transport process. (Ref Guyton) Glucose transport maximum (TmG): The maximal rate of reabsorption of glucose from the glomerular filtrate; it amounts to approximately 375 mg/minute in humans. Table: transport Maximum of different substances Substance Transport Maximum Glucose 375 mg/min Amino acids 1.5 mM/min Plasma protein 30 mg/min Creatinine 16 mg/min Para-aminohippuric acid 80 mg/min (Ref Guyton)
  34. 34. 6. Renal Physiology 34 PLASMA LOAD What do you mean by renal plasma load? DU Ju-10,11 Short notes: Plasma load DU Ju-06 The plasma load of a substance means the total amount of that substance present in plasma that passes through the Kidney in each minute. Plasma load = Renal plasma flow × Plasma concentration of the substance Example: Plasma conc. of glucose = 100 mg/100ml Rate of plasma flow through both kidneys = 650 ml/min So, plasma load of glucose = 100 mg/100ml x 650 ml/min = 650 mg/minute (Ref Guyton) TUBULAR LOAD Define the terms tubular load. SUST Jan 16, DU Ju-13, 11,10 Calculate tubular load of glucose if plasma glucose 200 mg/dl. GFR = 127 ml/minute. DU May 15 Calculate tubular load of glucose if plasma glucose 120 mg/dl. GFR = 120 ml/minute and Renal plasma flow = 650 ml/minute. DU Ju-13,06 Total amount of substance that passes through filtration membrane into nephrons each minute is called tubular load. Tubular load = GFR x Plasma concentration of the substance Example:  Tubular load of glucose = 125 mg/min  Tubular load urea = 33 mg/min RENAL TUBULAR SECRETION Renal tubule secretes hydrogen ion, potassium ion, uric acid, ammonia and creatinine. Uric acid and creatinine are secreted by proximal convoluted tubule. Creatinine is filtered, secreted and reabsorbed. The amount of secretion and reabsorption of creatinine is equal. Therefore, the amount of creatinine that is filtered is excreted through the urine. Secretion of potassium ion Potassium ion is secreted from distal tubule and collecting duct. Potassium ion is secreted from the blood into the tubular fluid by principal cells in two steps. First, K+ uptake across the basolateral membrane occurs via the action of sodium-potassium ATPase pump. In the second step, potassium ion leaves the cells by diffusion. Although the negative potential inside the cells tends to retain the potassium ion within the cell, the electrochemical gradient across the apical membrane favors potassium ion secretion from the cell into the tubular fluid.
  35. 35. 6. Renal Physiology 35 Special Viva Questions Explain: If the tubular load of glucose is above the TmG value, then excess glucose is not reabsorbed but excreted in the urine. The filtered load of glucose is 125 mg/minute. When GFR is largely increased or plasma glucose level is largely increased, the filtered load of glucose increases above 375 mg/minute and the excess glucose filtered is not reabsorbed and passes into the urine. When the plasma glucose concentration is 100 mg/100 ml and the filtered load is normal (125 mg/minute ), there is no loss of glucose in urine. When the plasma concentration of glucose rises above 200 mg/100 ml, increasing the filtered load to about 250mg/minute, a small amount of glucose appear in the urine. This point is termed the threshold for glucose. This appearance of glucose in urine occurs before the transport maximum is reached, because: 1. Not all nephrons have the same transport maximum for glucose. 2. Some of the nephrons excrete glucose before others have reached their transport maximum. The overall transport maximum for the kidneys which is normally about 375 mg/minute is reached when all nephrons have reached their maximal capacity to reabsorb glucose. In diabetes mellitus, Tubular load> TmG. So, glucose appears in urine (Reference: Guyton, 13th , 351-352) Why are large amounts of solutes filtered and then reabsorbed by the kidneys? 1. High glomerular filtration rate allows the kidneys to rapidly remove waste products from the body that depend primarily on glomerular filtration for their excretion. Most waste products are poorly reabsorbed by the tubules and therefore, depend on a high GFR for effective removal from the body. 2. High GFR allows all the body fluids to be filtered and processed by the kidney many times a 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. MCQ Q. The cells of distal convoluted tuble-(DU-15M) a. reabsorb most of the potassium ion in glomerular filtrate b. contain main target cells for ADH c. from NH4 + ions d. reabsorb most of the chloride ion in glomerular filtrate e. reabsorb sodium ion in exchange for hydrogen ions. Ans. a-F, b-T, c-T, d-T, e-T Q. Substances secreted by proximal convoluted tuble are-(DU-15M) a. chloride ion b. urate c. bicarbonate d. PAH e. Hydrogen ion Ans. a-F, b-T, c- F, d-T, e-T Q. Substances that are freely filtered but no reabsorbed by the kidney include-(DU-15M) a. creatinine b. inulin c. glucose d. urea e. bicarbonate Ans. a-T, b-T, c-F, d-F, e-F Q. Substances that have no transport maximum process include-(DU-15J) a. amino acid b. plasma protein c. creatinine d. chloride e. urea Q. Thin segment of loop of henle is highly permeable to (DU-15J) a. sodium b. urea c. wate d. glucose e. amino acid Ans. a-T, b-T, c-T, d-F, e-F Q. Substances completely reabsorbed in the proximal tubule are-(DU-14Ju) a. Water b. Na+ c. uric acid d. glucose e. PAH Ans. a-F, b-F, c-F, d-T, e-F Q. Following substances are completely reabsorbed in PCT (RU Nov 17) a. Glucose b. Amino acids c. Water d. PAH e. urea
  36. 36. 6. Renal Physiology 36 Ans. a-T, b-T, c-F, d-F, e-F Q. Proximal tubule of kidney-(DU-14Ju) a. is situated in cortex b. reabsorbs sodium completely c. contains macula densa d. reabsorbs 95% water e. secretes H+ Ans. a-T, b-F, c-F, d-F, e-T Q. The cells of the distal convoluted tuble-(SU-14Ju) a. reabsorbs about 50% of water flitered by teh blomeruli b. secrete hydrogen ions into the tubular lumen c. from NH4 + . d. reabsorb sodium in exchange for potassium ions e. determine the final composition of urine Ans. a-F, b-T, c-T, d-T, e-T Q. Secretion in proximal tubule are-(DU-14J) a. amino acid b. bile salt c. oxalate d. urate e. sodium ion Ans. a-F, b-F, c-F, d-T, e-F Q. Substance completely reabsorbed by kidney-(DU- 13Ju) a. water b. Na ion c. uric acid d. glucose e. PAH Ans. a-F, b-F, c-F, d-T, e-F Q. Water reabsorption in kidney is-(DU-13Ju) a. obligatory in PCT b. observed in all parts of renal tubules c. ADH dependent in DCT and CT d. cyclic GMP dependent e. about 65% in PCT Ans. a-T, b-F, c-T, d-F, e-T Q. Site of ADH action on the nephron is-(DU-13Ju) a. proximal tubule b. collecting tubule c. vasa recta d. loop of Henle e. Ans. a-F, b-T, c-F, d-F, e-T Q. Substances partially reabsorbed in the proximal convoluted tubule are- (DU-13J) a. Na+ b. water c. glucose d. amino acid e. urea Ans. a-T, b-T, c-F, d-F, e-T Q. Substances partially reabsorbed in the PCT are- (DU-11Ju) a. Water (T) b. Na+ (T) c. Amino acid (F) d. Glucose (F) e. PAH (F) Q. The following substance are secreted by teh renal tubular epithelium- (DU-13J) a. ilulin b. H+ c. creatinine d. amino acid e. PAH Ans. a-F, b-T, c-F, d-T, e-T Q. Water reabsorption is kidney is-(DU-12J) a. obligatory in PCT (T) b. ADH dependent (F) c. ADH dependent (F) d. cyclic GMP dependent (F) e. about 65 in PCT (T) Q. Tm limited reabsorption of a substance implies that: (CU:Ja07) a. reabsorption is active b. reabsorption is related to tubular transit time c. reabsorption is complete below a threshold value d. renal clearance falls with its plasma concentration e. excretion rate is zero until Tm value reached Ans. a-T, b-T, c-T, d-T, e-F Q. In absence of ADH, maximum water is reabsorbed in the-(RU: Ju06/05k) a. PCT b. Loop of Henle c. distal tubules d. cortical collecting ducts e. medullary collecting duct Ans. a-T, b-F, c-F, d-F, e-F Q. Regarding PCT-(RU: Ju-06) a. Maximum water is reabsorbed b. acidification of urine occurs c. secret H+ in exchange of Na+ d. glucose is reabsorbed e. presence of epithelial brush border Ans. a-T, b-F, c-T, d-T, e-T Q. Principal cell of collecting duct are responsible: (RU: Ja-07) a. For Na+ reabsoprtiong b. For H+ secretion c. For HCO3 - preservation d. For water reabsorption e. For production of renin Ans. a-T, b-T, c-T, d-F, e-F Q. Renal tubules normally reabsorbed-(RU: Ja-05) a. about 99% of the glomerular filtrate b. all filtered HCO3 - in respiratory acidosis c. all filtered amino acid d. More K+ than Cl- e. all filtered plasma protein Ans. a-T, b-T, c-T, d-F, e-T Q. Renal tubules normally reabsorb (DU Jan17) a. about 85% of the glomerular filtrate b. all filtered amino acid. c. all filtered glucose d. all filtered bicarbonate ion.
  37. 37. 6. Renal Physiology 37 e. all filtered Na Ans.a)F b)T c) T d)F e)F Q. Aldosterone acts on the following part renal tubule (DU Jan17) a. proximal convoluted tubule b. ascending limb of loop of Henle c. early part of distal tubule d. collecting tubule e. collecting duct Ans. a) F b) F c)T d) F e) F Q. Substance completely reabsorbed from PCT are- (RU: Ju-06) a. glucose b. Na+ c. K+ d. amino acid e. acetone Ans. a-T, b-F, c-F, d-T, e-T Q. Substances partially reabsorbed in proximal convoluted tubule is a. Water b. Na + c. amino acid d. glucose e. PAH Ans. a) T b) T c) F d) F e) T Q. Hormones acting on kidneys are- (DU-15Ju) a. ADH b. atrial natriuretic peptide c. aldosterone d. renin e. ACTH Ans. a-T, b-T, c-T, d-F, e-F Q. Following hormones act on proximal tubule-(DU- 13Ju) a. aldosterone (F) b. angiotensin II (T) c. ADH (F) d.. prostaglandin (F) e. bradykinin (F) Q. Hormones acting on the kidney are-(DU-11J) a. Aldosterone (T) b. Parathormone (T) c. ADH (T) d. Growth hormone (F) e. Thyroxine (F) Q. The hormones that regulate the renal tabular re- absorptions are- (DU-10Ju) a. ANP (T) b. T3, T4 (F) c. PTH (F) d. Brain natriuretic peptide (T) e. Angiotensin-II (F) Q. The hormones acting on kidney are- (DU-11Ju) a. Parathormone (T) b. Thyroxine (F) c. Angiotensin II (T) d. Aldosterone (T) e. Growth hormone (F) Q. The following hormones and autocoids decrease GFR (DU-11Ju) a. Norepinephrine (T) b. Endothelin (F) c. Prostaglandin (F) d. Endothelial derived nitric oxide (F) e. Bradykinin (F) Q. Administration of ADH: (CU: Ja.07) a. decreases water loss by lungs b. decreases water loss by kidney c. increases respiration d. decreases reabsorption of Na+ by PCT e. increases reabsorption of water by distal tubule Ans. a-F, b-T, c-F, d-F, e-T Q. In the presence of ADH, maximum water is reabsorbed in the- (RU: Ja-06) a. DT b. PCT c. LH d. CCT e. MCT Ans. a-F, b-F, c-F, d-T, e-F Q. Name the hormones acting on kidney-(RU: Ju-05) a. aldosterone b. angiotensin II c. ADH d. 1.25 dihydroxycholecalciferol e. erythropoietin Ans. a-T, b-T, c-T, d-T, e-T Q. The hormones acting on kidneys are (DU May 16) a. angiotensin II b. aldosterone c. Growth hormone d. parathormone e. thyroxin Ans. a-T, b-T, c-F, d-T, e-F Q. Water reabsorption in kidney is (DU Nov 16) a. obligatory in PCT b. about 65% in PCT c. ADH dependent in PCT d. observed in all parts of renal tubules e. cyclic AMP dependent Ans.a)Tb)Tc)Fd)Fe)T Q. Water reabsorption occur in (RU Nov 16) (a) proximal] convoluted tubules (b) descending limb of L.H (c) ascending limb of L.H (d) early part of D.C.T (e) collecting tubules Ans. a-T, b-T, c-F, d-F, e-T Q. Hormones acting on kidneys are (DU Nov 17) a. ADH b. atrial natriuretic peptide c. aldosterone d. renin e. ACTH Ans. a-T, b-T, c-T, d-F, e-F Q. Hormones act on kidney (RU Nov 16)
  38. 38. 6. Renal Physiology 38 (a) ADH (b) erythropoietin (c) renin (d) parathormone (e) aldosterone Ans. a-T, b-F, c-F, d-T, e-T Q. Administration of ADH: (CU May-16, Jan 09) a) decreases water loss by lungs b) decreases water loss by kidney c) increases perspiration d) decreases reabsorption of Na + by PCT e) increases reabsorption of water by distal tubule Ans: a) F b) T c) F d) F d) T Q. Substance secreted by renal tubules (RU May 17) (a) HCO3 - (b)H+ (c) Cl- (d) K+ (e) Na+ Ans. a-F, b-T, c-F, d-T, e-F Q. Primary active transport related molecules in renal tabular cells are (RU Nov 17) (a) Sodium-potassium ATPase (b) Sodium-glucose co-transporter (c) Glucose transporter (d) Proton pump (e) Hydrogen-potassium ATPase Ans. a-T, b-F, c-F, d-T, e-T Q. Tubular reabsorption: (CU Jan10) (a) Is highly selective (b) Is very large relative to excretion (c) Is only by passive mechanism (d) of water is active process (e) from DCT is obligatory Ans: (a) T (b) T (c) F (d) F (e) F Q. Proximal tubule: (CU May-16) a) reabsorb 65% na and H20 b) is the site of glomerulotubular balance c) fluid is slightly iso-osmotic d) reabsorbed 50% of filtered glucose e) secrete H+ and K+ Ans: a) T b) T c)T d) F d) T Q. H+ secretion in proximal tubule is associated with: CU/Jan 12 (a) Excretion of k+ (b) Excretion of Na+ (c) Reabsorption of HCO+ (d) Reabsorption of Ca+ (e) Reabsorption of HPO+ Ans: (a) F (b) F (c) T (d) F (e) F Q. Renal tubules normally reabsorb: (CU Jan 09) (a) All filtered glucose (b) All filtered plasma proteins (C) About 60% filtered of water (d) More k+ ion than C- l ion (e) All filtered amino acid Ans: (a)T (b) T (c) F (d) F (e) T Q. Aldosterone on renal tubule normal reabsorb: (CU May 16) a) All filtered glucose b) All filtered plasma proteins c) About 5-10% of filtered water d) More K+ ion than CI- ion e) Na+ ,Cl- ion & water Ans: a) F b) F c) T d) F d) T 6. Formation of Urine Mechanism of Urine formation Discuss the mechanism of formation of urine RU MAY 18, CU May 16 Mention the basic mechanisms of formation of urine. DU Nov16 What are the process involved in urine formation? CU Jan 15, RU NOV 16, JUL14, 11, DU Ju-11, SUST Jan 16 Describe the processes of urine formation. DU Ja-08, Ja-09 Urine formation takes place by the following three mechanisms- A. Formation of glomerular filtrate B. Tubular reabsorption C. Tubular secretion Urine Excretion = Filtration – Reabsorption + Secretion (Reference: Guyton, 13th , 331) A. Filtration (formation of glomerular filtrate): Due to the effective filtration pressure (about 10 mmHg) glomerular filtrate is formed through the glomerular membrane. Normally glomerular filtration rate is 125ml/min or 180 liter/day. B. Tubular reabsorption:
  39. 39. 6. Renal Physiology 39 Parts of the tubule reabsorption PCT • 65 to 70% of the glomerular filtrate is reabsorbed. • glucose, amino acids, vitamins are reabsorbed completely. • 25 to 30 % of the glomerular filtrate remains. Descending limb of LH • Reabsorption of water and Na+ take place. • 15% of glomerular filtrate absorbed • 15 % of the glomerular filtrate remains. Ascending limb of LH Reabsorption of • sodium, chloride, and potassium. • Mg++ , Ca++ , Na+, and K+ , DCT • Water reabsorption occurs under the influence of ADH. • Na+ & Cl- are also reabsorbed. Collecting system • Reabsorption of Na+ and water (due to ADH) Takes place. • 0.7% filtrate passes as urine. C. Tubular secretion: Parts of the tubule secretion PCT K+ , H+ creatinine, drugs NH4 + is Descending limb of LH Na+ by passive diffusion. Ascending limb of LH Urea & H+ by passive diffusion. DCT • K+ (controlled by Aldosterone). • H+ Collecting system Secretion of K+ and NH4 + by exchange pump. Describe and show the relationship among the processes of filtration, secretion, and re- absorption. • Filtration: Blood is filtered – Proteins and other large molecules stay in blood. – Water and small solutes are sent to the excretory system. This creates filtrate
  40. 40. 6. Renal Physiology 40 • Reabsorption: Filtrate has water and other ions (glucose, salts, amino acids) that the body still needs. As a result, these substances are taken back through active or passive means. The water and ions move into the tissue fluid or into the neighboring capillaries/arterioles • Secretion: Opposite of reabsorption. – Molecules are moved back into the filtrate (hormones, hydrogen ions) MCQ Q. Urine formation result from-(DU-14J) a. glomerular filtration b. tubular reabsorption c. ultrafiltration of afferent arteriole d. tubular secretion e. secretion on efferent arteriole Ans. a-T, b-T, C-F, d-T, e-F Q. Urine formation results from-(DU-13J) a. glomerular filtration b. tubular reabsorption c. peritubular capillary secretion d. ultrafiltration of afferent arteriole e. tubular secretion Ans. a-T, b-T, c-F, d-F, e-T Q. Urine formation results from (DU May 16) a glomerular filtration b tubular reabsorption c ultrafiltration of afferent arterioles d secretion of efferent arterioles e tubular secretion Ans. a-T, b-T, c-F, d-F, e-T 7. Urinary concentration (Counter Current Mechanism) The normal kidney has tremendous capability to vary the relative proportions of solutes and water in the urine in response to various challenges. When there is excess water in the body and body fluid osmolarity is reduced, the kidney can excrete urine with an osmolarity as low as 50 mOsm/L, a concentration that is only about one sixth the osmolarity of normal extracellular fluid. Conversely, when there is a deficit of water and extracellular fluid osmolarity is high, the kidney can excrete urine with a concentration of 1200 to 1400 mOsm/L. Equally important, the kidney can excrete a large volume of dilute urine or a small volume of concentrated urine without major changes in rates of excretion of solutes such as sodium and potassium. This ability to regulate water excretion independently of solute excretion is necessary for survival, especially when fluid intake is limited. [Guyton] FORMATION OF DILUTE URINE What are the basic principles of concentrated urine formation? RU JUL10, DU Briefly discuss the mechanisms of formation of dilute urine. CU Nov 17, 15, DU May 17, CU Jan 16 'Kidney excretes excess water by forming dilute urine'- explain it in short. DU Nov 15, Ju-14, 11, 10
  41. 41. 6. Renal Physiology 41 Discuss briefly the reabsorption of water from different parts of the kidney. DU Jan17 1. When water removal is needed, no ADH is released, so the Distal and Collecting Tubules will not reabsorb water but solute will be reabsorbed > water moves out with urine with low ion solute content > dilute urine 2. Urine osmolarity will be as low as 50 mosm/L in such cases The mechanism and pathway of formation of dilute urine through the nephron is as follows: Site Amount of filtrate reabsorbed Solute reabsorbed Result of tubular fluid PCT 65-70% yes Isotonic (300 mosmole/L). Descending limb of Henle 15% no Hyperosmotic solution. At the tip of the LH the osmolarity reaches to some 1200 mosmole/L. Ascending limb of loop or Henle 0% Yes (Na+ , Cl- ) Hyposmotic solution. Osmolarity: 100 mosmole/L. Distal tubule and Collecting system No or very small amount of water reabsorption in the absence of ADH Yes(Na+ , Cl- urea, ) Osmolarity: 50 mosmole/L. The remaining tubular fluid will excreted as dilute urine with this low osmolarity (50 mosmole/L) with the urine volume of about 20 liter/day or 16 ml/minute Figure: Formation of dilute urine FORMATION OF CONCENTRATED URINE Discuss the mechanism of formation of concentrated urine. CU May 17, Jul 14 State how urine is concentrated in collecting duct? RU MAY 18,16, JAN 14 ADH hormone and the countercurrent mechanism helps in concentrated of urine A. In the presence of ADH, more than 99% of the water in filtrate may be reabsorbed
  42. 42. 6. Renal Physiology 42 1. ADH is released  reabsorbtion of more water in DCT and Collecting system concentrated urine. 2. Urine osmolarity will be as high as 1400 mosm/L in such cases The mechanism and pathway of formation of concentrated urine through the nephron is as follows: Site Amount of filtrate reabsorbed Solute reabsorbed Result of tubular fluid PCT 65-70% yes Isotonic (300 mosmol/L). Descending limb of Henle 15% no hyperosmotic solution. At the tip of the LH the osmolarity reaches to some 1200 mosmole/L. Ascending limb of loop or Henle 0% Yes (Na+ , Cl- ) hyposmotic solution. Osmolarity: 100 mosmol distal tubule 5-10% (In the presence of ADH) Yes (Na+ , Cl- ) Collecting system 14.3% (In the presence of ADH) Yes(Na+ , Cl- urea, ) Osmolarity: Hypertonic (up to 1400 mosmol/L) The remaining only 0.3% tubular fluid will excrete as concentrated urine, with this high osmolariy up to 1400 mosmol /L). B. The countercurrent mechanism THE COUNTER-CURRENTS MECHANISM What is countercurrent mechanism? CU May 17, DU Ju-13, RU May 17, RU JUL09, 08 JUL12, SUST Jul 12 Give the hypothesis of countercurrent mechanism. DU Jan-12 Write about the genesis of hyperosmolarity of renal medullary interstitium. RU MAY 15, DU Jan-12 Discuss about the counter-current mechanism. DU Ja-12, 08 It is a system in which inflow runs parallel to, counter to, and in close proximity to outflow. (Ganong) Counter-currents system produces (Countercurrent Multiplier) and maintain (countercurrent exchanger at Hyperosmotic Renal Medulla. • The two limbs of Henle's loop are a Countercurrent Multiplier • The two limbs of the vasa recta are countercurrent exchanger
  43. 43. 6. Renal Physiology 43 Osmotic gradient in the medulla is useful in producing concentrated urine. COUNTERCURRENT MULTIPLIER Countercurrent multiplication is a hypothesis describing the mechanism whereby urine is concentrated in the nephron. Initially proposed in the 1950s by Gottschalk and Mylle. Definition The repetitive reabsorption of sodium chloride by the thick ascending loop of Henle and continued inflow of new sodium chloride from the proximal tubule into the loop of Henle is called countercurrent multiplier Loop of Henle as Countercurrent Multiplier  The descending loop of Henle: o Is relatively impermeable to solutes o Is permeable to water  The ascending loop of Henle: o Is permeable to solutes o Is impermeable to water  A distinctive feature of the tubule is the sharp bend at the loop of Henle (Hair pin bend) o Because of the bend, tubule fluid moves downward into regions of increasing osmotic pressure o After the bend the tubule fluid moves upward through regions of decreasing osmotic pressure The kidney is able to produce the high osmotic gradient because the loop of Henle’s this hair pin turn. It is the thin descending limb and the entire ascending limb (thin and thick) that are involved in the countercurrent mechanism. Only the juxtamedullary nephrons with long loops of Henle are involved in the countercurrent mechanism Mechanisms Explain how the countercurrent mechanism in the kidney operate to produce hypertonic urine. RU May 17, JUL12, 11 Narrate the mechanism that produces hyper osmotic renal medullary interstitium. DU Ju-13, Ja-12, 11, Ju-09, State the mechanism that produce hyper osmotic renal medullary interstitium. RU JUL10 Explain the mechanism of production of gradient of hyperosmolarity of medulla. How this gradient, of hyperosmolarity of medulla is maintained. RU JUL08 The osmotic gradient in medulla is produced by 3 separate flows: 1. Pump –Na+ is pumped out of the ascending tubule by active transport (Cl- accompanies it to keep the flow electrically neutral) 2. Equilibration- Water leaves the descending tubule by osmosis (attracted by the high osmotic pressure in the interstitial fluid) 3. Shift- Glomerular filtration, driven by the blood pressure, constantly pushes new fluid into the tubule
  44. 44. 6. Renal Physiology 44 Steps
  45. 45. 6. Renal Physiology 45 1. the tubule initially filled with isotonic (300 mosm/L) fluid from PCT. (Figure A) 2. Na+ is pumped out of the ascending loop, raising the osmotic pressure in medullary interstitium and lowering it in the tubule. Note that the maximum gradient (inside to out) is 200 mosm/L. (Pump) (Figure B) 3. Water flows out of the descending tubule by osmosis, raising the osmotic pressure in the descending tubule to 400 mosm/L (eequilibration) (Figure C) 4. Fresh fluid enters from the glomerulus, pushing concentrated fluid (400 mosm/L) into the ascending limb (Shift) (Figure D) 5. In the 2nd round the Na pump produces another 200 mosm/L gradient across the membrane, but it is starting from a more concentrated solution, so the external osmolarity rises to 500 mosm/L. (Pump) (Figure E) 6. The 3rd round of Na pumping raises interstitial concentration to 700 mosm/L, and so on. (Pump) (Figure F) 7. with sufficient time, this process gradually traps solutes in the medulla and multiplies the concentration gradient established by the active pumping of ions out of the thick ascending loop of Henle, eventually raising the interstitial fluid osmolarity to 1200 to 1400 mOsm/L. (Pump). In times of dehydration, Collecting Tubules leak urea to interstitial space, further increasing water retention by increasing osmolarity. Role of Urea State how urine is concentrated in collecting duct? RU JAN 14 Absorption of urea in the collecting tubules, under the influence of ADH, enhances the concentration gradient formed in the medullary interstitium. (Guyton) Benefits of Countercurrent Multiplication
  46. 46. 6. Renal Physiology 46 Efficiently reabsorbs solutes and water before tubular fluid reaches DCT and collecting system. (Guyton) Single effect The ascending limb of the loop of Henle transports solutes (NaCl) out of the tubule lumen with little or no water, generating an hyperosmotic medullary interstitium and delivering an hyposmotic tubule fluid to the distal tubule. This is called the "single effect". The osmolarity of the interstitium rises progressively from cortex to medulla and papilla through multiplication of the "single effect" by countercurrent flow in the branches of the loop: The single effect in fluid processed by loop segments located near the tip of the papilla occurs in fluid already subject to the single effect when the fluid was in loop segments located closer to the cortex. Why called the "single effect"? The model is called the "single effect" model because the osmolarity gradient is created by a series of the two discrete steps (single effects). • First step: a concentration step in which the solute pump creates a 200 mosmoles/L water gradient at each transverse segment. • Second step: a flow step in which tubular fluid courses through the loop. By repeating these two steps, the dynamic process of counter current multiplication is achieved. Variables that affect tip osmolarity The three variables that most affect tip osmolarity are … 1. the strength of the ascending thick limb's active transport pump 2. the length of the loop of Henle. 3. the flow rate of tubular fluid through the nephron 1. Pump strength: The pump strength of the active transporter in the ascending limb of the loop of Henle can alter tip osmolarity. "Loop" diuretics, extensively used in medicine to reduce edema (the pathological accumulation of extracellular fluid), decrease salt reabsorption from the thick ascending limb of the loop of Henle. This means that the transport of the solutes, Na+ and Cl- , out of the ascending limb is reduced. (Hint: Using your model from part I, move solutes to a gradient that is only 100 mOsm with each step. This represents reduced pump strength.) 2. Length of the Loop of Henle: A longer loop of Henle will function to produce a greater concentration of urea and salt in the medulla. The higher concentration gradient enables the removal of more water as fluid moves through the collecting duct. • Animals with a need for very concentrated urine (such as desert animals) have very long loops of Henle to create a very large osmotic gradient resulting in very little water loss. • Animals that have abundant water on the other hand (such as beavers) have very short loops. The vasa recta have a similar loop shape so that the gradient does not dissipate into the plasma. The flow rate of tubular fluid through the loop of Henle can affect tip osmolarity by moving fluid through the loop faster. COUNTERCURRENT EXCHANGER There are two special features of the renal medullary blood flow that contribute to the preservation of the high solute concentrations: 1. The medullary blood flow is low, accounting for less than 5 per cent of the total renal blood flow. This sluggish blood flow is sufficient to supply the metabolic need of the tissue but help to maintain solute loss from the medullary interstitium.. 2. The vasa recta serve as countercurrent exchangers, minimizing washout of solutes from the medullary interstitium.
  47. 47. 6. Renal Physiology 47 (Guyton, SA, 13th , 485) Vasa recta as countercurrent exchangers Write down the importance of vasa recta in forming concentrated urine. DU may 15 Blood enters and leaves the medulla by way of the vasa recta at the boundary of the cortex and renal medulla. The vasa recta, like other capillaries, are highly permeable to solutes in the blood, except for the plasma proteins. As blood descends into the medulla towards the papillae, it becomes progressively more concentrated, partly by solute entry from the interstitium and partly by loss of water into the interstitium. By the time the blood reaches the tips of the vasa recta, it has a concentration of about 1200 mOsm/L, the same as that of the medullary interstitium. As blood ascends back towards the cortex, it becomes progressively less concentrated as solutes diffuse back out into the medullary interstitium and as water moves into the vasa recta. Although there are large amounts of fluid and solute exchange across the vasa recta, there is little net dilution of the concentration of the interstitial fluid at each level of the renal medulla because of the U shape of the vasa recta capillaries, which act as countercurrent exchangers. Thus, the vasa recta do not create the medullary hyperosmolarity, but they do prevent it from being dissipated. The U-shaped structure of the vessels minimizes loss of solute from the interstitium but does not prevent the bulk flow of fluid and solutes into the blood through the usual colloid osmotic and hydrostatic pressures that favor reabsorption in these capillaries. Under steady-state conditions, the vasa recta carry away only as much solute and water as is absorbed from the medullary tubules and the high concentration of solutes established by the countercurrent mechanism is preserved. (Guyton, SA, 13th , 485-486) The major factors that contribute to the buildup of solute concentration into the renal medulla are as follows: What are the factors that produce hyperosmotic renal medullary interstitium? SUST Jul 12 1. Active transport of sodium ions and cotransport of potassium, chloride and other ions out of the thick portion of the ascending limb of the loop of Henle into the medullary interstitium. 2. Active transport of ions from the collecting ducts into the medullary interstitium. 3. Facilitated diffusion of large amounts of urea from the inner medullary collecting ducts into the medullary interstitium. Diffusion of only small amounts of water from the medullary tubules into the medullary interstitium, far less than the reabsorption of solutes into the medullary interstitium. [Reference: Guyton]
  48. 48. 6. Renal Physiology 48 Osmole: Concentration of osmotically active particles is expressed in osmole. Osmolarity: Number of osmoles per liter of solution is called osmolarity. Osmolality: Number of osmoles per kilogram of solvent is called osmolality. Value of plasma osmolarity: 300 mOsm/liter. Value of osmolarity of glomerular filtrate which is just filtered: About 300 mOsm/liter. Value of osmolarity of urine: 600 mOsm/liter. Range is 500-800 mOsm/liter. OBLIGATORY URINE VOLUME What do you mean by obligatory urine volume? CU May 17,Jan 16, Nov 15, DU Jan17, Ju-11, 15  The obligatory urine volume is the volume of urine that must be excreted each day to rid the body of waste products of metabolism and ions that are ingested.  A normal 70 kg human must excrete about 600 milliosmoles of solute each day. The maximal urine concentrating ability is about 1200 mOsm/L. Therefore, obligatory urine volume can be calculated by: Obligatory solute excretion/day ------------------------------------------------------------------ Maximum ability of kidney to concentrate the urine 600 mOsm/day = --------------------- 1200 mOsm/L = 0.5 liter/day. (Reference: Guyton, 13th , 373) DISORDERS OF URINARY CONCENTRATING ABILITY 1. Inappropriate secretion of ADH (too much or too little secretion of ADH). Failure to produce ADH from hypothalamus or to release ADH from the posterior pituitary causes “central” diabetes insipidus. These conditions may follow a) head injury b) infections or c) congenital abnormalities In these conditions, a large volume of dilute urine is formed. 2. Impairment of countercurrent mechanism. 3. Inability of the distal tubule, collecting tubule and collecting ducts to respond to ADH. There are circumstances in which normal or elevated levels of ADH are present but the renal tubular segments cannot respond appropriately. This condition is called “nephrogenic”diabetes insipidus because the abnormality resides in the kidneys. This condition results in the formation of a large volume of dilute urine. Special Viva Question
  49. 49. 6. Renal Physiology 49 Q:Explain-very low velocity of blood flow in the vasa recta helps preservation of medullary gradient. Answer: Very low velocity of blood in the vasa recta helps the blood of vasa recta to unload its Na load in the medullary interstitium satisfactorily and thus to retain the medullary gradient Q:Upon which concentrating ability of the kidney depends Answer: Maximum concentrating ability of the kidney is determined by 1. the level of ADH 2. the osmolarity of the renal medulla interstitial fluid Q: What is the maximum urine production rate daily? Answer: When there is a large excess of water in the body, the kidney can excrete as much as 20 L/day of dilute urine, with a concentration as low as 50 mOsm/L. Urine volume increases to about six times normal within 45 minutes after the water has been drunk. MCQ Q. Countercurrent mechanism involves with- (DU-15J) a. vasa recta b. peritubular arteries c. the loop of Henle d. glomerulus e. collecting duct Ans. a-T, b-F, c-T, d-F, e-F Q. Countercurrent exchange mechanism includes- (DU- 14Ju) a. proximal tubule b. vasa recta c. loop of Henle d. distal tubule e. collecting duct Ans. a-F, b-T, c-F, d-F, e-F Q. The ability of the kidney to concentrate urine is due to (SU-14Ju) a. presence of juxtamedullary nephrons b. presence of countercurrent multiplier c. presence of countercurrent exchange d. presence of ADH e. presence of aldosterone Ans. a-T, b-T, c-T, d-T, e-F Q. Hyperosmolarity of renal medulla is due to increased concentration of (DU Nov 17) a. K+ b. glucose c. water d. NaCl e. urea Ans. a-F, b-F, c-F, d-T, e-T Q. Hyperosmolarity of medulla is produced by: (RU: Ju06) a. Na b. K c. urea d. creatinine e. Cl Ans. a-F, b-F, c-T, d-F, e-F Q. To produce a concentrated urine, ADH-(RU:Ja-06) a. increases the aquaporin the PCT b. increases the movement of aquaporin-2 in CD c. binds the receptors in CD cells. d. increases Na reabsorption from PCT e. produces hyperosmotic medullary interstitium Ans. a-F, b-T, c-T, d-F, e-F Q. Following structure take part in the formation of concentrated urine (DU Nov 17) a. loop of Henle b. early distal convoluted tubule c. collected duct d. proximal convoluted tubule e. Vasa recta Ans. a-T, b-T, c-F, d-F, e-T Q. Urea is transported through (DU Jan17) a. proximal tubule b. thin limb of loop of Henle c. thick limb of loop of Henle d. distal tubule e. cortical collecting tubule Ans. a) F b) T c) F d)F e) F 8. Acidification of Urine The pH of blood plasma is kept within normal limits by controlling the excretion of H+ in the urine and the re-absorption of bicarbonate into blood plasma. If acid (H+ ) is excreted in the urine, it is in effect removed from the blood when an equal quantity of bicarbonate is added to the blood. Bicarbonate (as a base) neutralizes hydrogen ions in the blood.
  50. 50. 6. Renal Physiology 50  If the blood is too acidic more hydrogen ions are excreted,  if the blood is too basic, then less hydrogen ions are excreted. HCO3 - + H+ <===> H2CO3 <===> CO2 + H2O The renal tubules excrete hydrogen ions by an unknown series of reactions into the tubular urine. The amount of hydrogen ions excreted is controlled by the concentration of H+ (pH), bicarbonate, and the partial pressure of CO2 (pCO2) in the blood plasma and by the amount of Na+ and bicarbonate in the developing urine. Hydrogen ions and sodium ions exchange places throughout the formation of urine. For every H+ which enters the urine, one sodium ion is reabsorbed from the urine into the blood and is conserved. For every H+ ion excreted and every Na+ ion conserved, one bicarbonate ion is also reabsorbed into the blood. The charges on sodium and bicarbonate are thus always balanced H+ SECRETION Why secrete H+ ? To 1. Provides a mechanism for the reabsorption of bicarbonate filtered by glomerulus. 2. Provides a mechanism to enable net hydrogen ion gain or loss for acid/base balance 3. Adjust excretion of H+ and HCO3 - to compensate for net retention or elimination of CO2, GIT losses of acid/base Factors The renal acid secretion is mainly regulated by the changes in the intracellular pCO2, potassium concentration, carbonic anhydrase activity and adrenocortical hormone concentration. Processes Involved in the Secretion of H+ into the Renal Tubules Name the processes involved in the secretion of H + into the renal tubules. RU JUL11 Name the processes involved in the secretion of H + into the renal tubules. RU NOV 15, JUL 14, 12 Give the processes of H + secretion in renal tubules. RU JAN10 The process of H+ secretion and HCO3 - reabsorption occurs throughout the nephron with the exception of the DLH The processes are - 1. Na+ - H+ counter transport:  The epithelial cells of the proximal tubule, the thick segment of ascending loop of Henle and the early distal tubule all secrete H+ into the tubular fluid by sodium-hydrogen counter- transport (secondary active transport)  About 95% H+ is secreted by Na counter transport.
  51. 51. 6. Renal Physiology 51 2. H+ -K+ ATPase pump:  in the DCT & CT by  5% Mechanism Illustrate the mechanism of secretion of hydrogen ions by the-renal tubules. DU Ju-10 H+ secretion in proximal and distal tubules In the Proximal tubule: • CO2, binds with H2O to form H2CO3 catalyzed by carbonic anhydrase. H2 CO3 dissociates into HCO3 and H+ CO2 + H2O <====> H2CO3 <===> HCO3 - + H+ • H+ is secreted into tubular lumen by Na+ -H+ counter transport (the energy is derived from Na+ -K+ pump). In the distal tubule: • In the intercalated cells, CO2 & H2O binds to form H2CO3 which dissociates into H+ & HCO3 • H+ is secreted into tubular lumen by a primary active transport called H+ -K+ ATPase. (Ref. Ganong) Acidification of Urine Mechanism (Fate of H+ secreted in renal tubule) How does the alkaline glomerular filtrate become acidic urine? DU Ju-12, 10, RU JUL 14, 12, 10 State the fate of H+ that is secreted in real tubules. RU NOV 15, JAN 11, 09 Name the acid substances present in urine. RU JAN10