Renal Physiology PDF

RENAL PHYSIOLOGY  Overview The kidneys represent the primary organs of homeostasis in the regulation of both volume & composition of body fluids & the excretion of metabolic waste products in urine. The kidneys are large, bean-shaped organs which lie on the dorsal side...

RENAL PHYSIOLOGY  Overview The kidneys represent the primary organs of homeostasis in the regulation of both volume & composition of body fluids & the excretion of metabolic waste products in urine. The kidneys are large, bean-shaped organs which lie on the dorsal side of the visceral cavity. They are protected by a tough fibrous coat called the renal capsule. Adipose (fatty) tissue surrounds the renal capsule & cushions the kidney. 1/11/2025 2  Components of renal system The renal system composed of Kidneys: formation of urine Ureters: transport urine from the kidneys to the bladder Urinary bladder: provides a temporary storage reservoir for urine Urethra: transports urine from the bladder out of the body 1/11/2025 3  Kidneys Bean-shaped, retroperitoneal, located in the abdominal cavity at the lumbar region. The right kidney is crowded by the liver & lies slightly lower than the left. Renal hilus: inlet/out let of ureters, arteries, veins, lymphatics and nerves At the top of each kidney there is adrenal gland (suprarenal gland). 1/11/2025 4  Kidneys… On a longitudinal section of kidney there are 2 distinct regions, cortex & medulla. The outer cortex surrounds darker triangular structures called pyramids which form the medulla. The inner part of the kidneys, the renal pelvis collects the urine from the calyces draining it into the ureter. 1/11/2025 5  Nephron § The basic functional unit of the kidneys. § Each kidney is made up of approximately 1 million nephrons, consisting: q Renal corpuscle Glomerulus Bowman’s capsule q Renal tubules Proximal convoluted tubule Loop of Henle Distal convoluted tubule 1/11/2025 6  Nephron… 1/11/2025 7  Types of Nephrons Cortical nephrons Juxtamedullary nephrons 85% of nephrons, Few in number, are located located in the cortex in the medullary region Have short loop of Have long loops of Henle Henle that deep the medulla, have extensive thin Supplied with segments peritubular capillaries Supplied with vasa recta Involved in the Involved in the production formation of diluted of concentrated urine urine. 1/11/2025 8  Types of Nephrons … Corticla nephrons Juxtamedullary nephron 1/11/2025 9 1/11/2025 10  Functions of the Urinary System 1. Regulate: Ø ABP by controlling blood volume & RAAS, RBC formation by producing EPO, Electrolytes concentration (Na+, K+, Ca2+, PO43-), ECF & blood volume, Acid-base balance, and Osmolality of the body fluid (300 Mosm/l) maintain the proper balance between water & salts. 2. Endocrine function: EPO, Calcitriol, PGE1 & PGE2. 3. Filter 200 liters of blood daily to eliminate toxins, metabolic wastes & excess ions. 4. Drug metabolism & detoxification of certain chemicals. 1/11/2025 11  Functions of the Urinary System… 5. Excretion: by forming urine, the kidneys help excrete wastes substances that have no useful function in the body. Some wastes excreted in urine result from metabolic reactions in the body. These include: – ammonia & urea from the breakdown of amino acids – bilirubin from the breakdown of hemoglobin – creatinine from the breakdown of creatine phosphate in muscle fibers and – uric acid from the breakdown of nucleic acids. Other wastes excreted in urine are foreign substances from the diet, such as drugs & environmental toxins. 1/11/2025 12  Functions of the Urinary System… 1. Filtration of the blood – Occurs in the glomerulus of the kidney nephron. – Contributes to homeostasis by removing toxins or waste. 2. Reabsorption of vital nutrients, ions & water – Occurs in most parts of the kidney nephron. – Contributes to homeostasis by conserving important materials. 1/11/2025 13  Functions of the Urinary System… 3. Secretion of excess materials – Assists filtration in removing material from the blood. – Contributes to homeostasis by preventing build-up of certain materials in the body (drugs, waste, etc). 4. Activation of Vitamin D – Vitamin D made in the skin is converted to Vitamin D3 by the kidney. – Active Vitamin D (D3) assists homeostasis by increasing calcium absorption from the digestive tract & reabsorption from renal tubules. 1/11/2025 14  Functions of the Urinary System… 5. Release of Erythropoietin (EPO) by the kidney – EPO stimulates new RBC production. – New RBC’s assist homeostasis by insuring adequate Oxygen & Carbon dioxide transport. 6. Release of Renin by the kidney – Renin stimulates the formation of a powerful vasoconstrictor called Angiotensin II – Angiotensin II assists homeostasis by causing vasoconstriction which increases blood pressure. 1/11/2025 15  Functions of the Urinary System… 7. Release of Prostaglandins – Prostaglandins dilate kidney blood vessels. – Dilated blood vessels contribute to homeostasis by maintaining blood flow in the kidneys. 8. Secretion of H+1 & reabsorption of HCO3-1 – Eliminates excess hydrogen ions & conserves buffer material such as bicarbonate. – Contributes to homeostasis by controlling acid/base conditions in body fluids 1/11/2025 16 Kidney Structures Teka-Renal 17  Kidney Structures… v Capsule – The outer membrane that encloses, supports and protects the kidney v Cortex – The outer layer of the kidney that contains most of the nephron, main site for filtration, reabsorption & secretion v Medulla – Inner core of the kidney that contains the pyramids, columns, papillae, calyces, pelvis and parts of the nephron not located in the cortex. 1/11/2025 18  Kidney Structures… v Renal Pyramids – Triangular shaped units in the medulla that house the loops of Henle and collecting ducts of the nephron. – Site for the counter-current system that concentrates salt and conserves water and urea. vRenal Column – A passageway located between the renal pyramids found in the medulla and used as a space for blood vessels. v Nephron – The physiological unit of the kidney used for filtration of blood and reabsorption and secretion of materials. 1/11/2025 19  Kidney Structures… v Renal Papilla – tip of the renal pyramid that releases urine into a calyx v Calyx – A collecting sac surrounding the renal papilla that transports urine from the papilla to the renal pelvis v Renal Pelvis – Collects urine from all of the calyces in the kidney v Ureter – Transports urine from the renal pelvis to the bladder 1/11/2025 20  Blood supply to kidneys The kidneys receive approximately 20% of the cardiac output (about 4 ml/min/g) one of the highest blood flow values. The profile of the vascular blood pressure in the renal circulation is characteristic, with a high capillary pressure: – that reflects the need to support the filtering capacity of the kidneys. 1/11/2025 21  Blood supply to kidneys… Renal Artery – Transports oxygenated blood from the heart and aorta to the kidney for filtration. Renal Vein – Transports filtered and deoxygenated blood from the kidney to the posterior vena cava and then the heart. 1/11/2025 22  Blood supply to kidneys… v Renal blood flow/RBF – The amount of blood flow to kidney per minute. – Arterial flow into and venous flow out of the kidneys follow similar paths. 1/11/2025 23  Blood supply to kidneys… 1/11/2025 Teka-Renal 24  Capillary Beds of the Nephron Every nephron has two capillary beds – Glomerulus – Peritubular capillaries or Vasa recta Each glomerulus is: – Fed by an afferent arteriole – Drained by an efferent arteriole 1/11/2025 25  Characteristics of the RBF 1. RBF = 1200 ml/min, or 20% of the CO. 94% to the cortex. 2. Two capillary beds: glomerulus and peritubular capillaries. 3. High hydrostatic pressure in glomerular capillary (about 60 mmHg) & low hydrostatic pressure in peritubular capillaries (about 13 mmHg). 4. It is unique that glomerular capillaries are found b/n 2 arterioles. 1/11/2025 26  Nerve supply to the kidneys Kidneys receive sympathetic nerve supply from the last thoracic & upper 2 lumbar segments of the spinal cord which relay in the paravertibral and mesentric ganglia. Sympathetic stimulation results in Constriction of arteries & arterioles →↓RBF (α-AR effect) Ø ↑Na reabsorption in renal tubules (α-AR effect) Ø ↑Renin secretion by JG-cells (β-AR effect) Dilation of efferent arterioles (β-AR effect) Parasympathetic supply from vagus nerve – function is not clear so far 1/11/2025 27  Process of urine formation - The mechanism by which nephrons clear the plasma of unwanted substances is: 1. Filters the plasma through the fenestrated glomerular membrane into renal tubules. 2. Reabsorption of needed substances , as the filtrate flows through the tubules. 3. Secretion of unwanted substances into the renal tubules. 1/11/2025 28  Process of urine formation… GFR  125 ml/min, 180L/day, about 1% is excreted 1/11/2025 29  Process of urine formation… 1/11/2025 30  Glomerulus and Bowman’s capsule 1/11/2025 31  Glomerular Filtration Filtration of fluid through the glomerular capillaries. The kidneys filter the body’s entire plasma volume 60 times each day. The filtrate contains: – all plasma components (except protein); water, nutrients, and essential ions to become urine (Plasma proteins are not filtered and are used to maintain oncotic pressure of the blood). Glomerulus is more efficient than other capillary beds because: Ø Its filtration membrane is significantly more permeable. Ø Glomerular blood pressure is higher ;it has a higher net filtration pressure. 1/11/2025 32  Glomerular filtration… Mechanism: bulk flow Direction of movement : - from glomerular capillaries to capsule space Driving force: - Pressure gradient (net filtration pressure, NFP) Types of pressure: Favoring Force: Capillary Blood Pressure (BP) Opposing Force: Blood colloid osmotic pressure(COP), and Capsule Pressure (CP) 1/11/2025 33  Filtration Membrane 1/11/2025 34  Glomerular membrane – Made up of 3 layers 1. Endothelial layer 2. Basement membrane 3. Epithelial cell (podocytes) – Thickness: 1 µm – Fenestrated, highly permeable – Allows the passage of all components of plasma except plasma proteins and blood cells 1/11/2025 35  Glomerular Filtration Rate (GFR) The amount of fluid filtered per minute in all nephrons of both kidneys. [GFR = 125 ml/min, or 180 L/day]. Filtration fraction (FF): the fraction of RPF (renal plasma flow) that becomes glomerular filtrate RBF = 1200 ml/min RPF = 55% of RBF, 650 ml/min FF = GFR/RPF, 125/650 = 19% Filtration pressure (FP): the net pressure forcing fluid to be filtered through the glomerular membrane. Determined by 1. Glomerular capillary pressure (60 mm Hg) 2. Glomerular capillary colloid osmotic pressure (32mm Hg) 3. Capsular hydrostatic pressure (18 mm Hg) FP = GCP – (GCCOP + CHP) = 60 – (32 + 18) = 10 mm Hg 1/11/2025 36 1/11/2025 37  Glomerular Filtration Pressure 1/11/2025 38  Factors affecting GFR 1. Filtration pressure 2. Permeability of the glomerular capillary membrane 3. Diameter of afferent arterioles: dilation ↑ GFR - Caffeine & diuretics dilate AA & ↑ GFR. - Sympathetic stimulation constricts AA and ↓ GFR. 4. Diameter of efferent arterioles: dilation ↓ GFR ↓RBF→↓GFR →↑Renin →↑Ang-II →EA constriction → ↑GFR 5. Concentration of plasma proteins: ↑Proteins → ↑PCOM →↓GFR 6. Renal blood flow: ↑RBF → ↑GFR 7. Arterial blood pressure: ↑ABP (limits) → ↑GFR 1/11/2025 39  Diameter of AA vs. GFR 1/11/2025 40  The Juxtaglomerular apparatus Initial portion of the DT passes in the angle between the AA & EA. Epithelial cells that come in contact with the arterioles are being modified & become secretory & collectively called macula densa. – secret PG - E1 & E2, vasodilator action on AA & EA The smooth muscles of AA & EA at the contact site become thickened and granulated called JG cells – responsible for the secretion of renin & erythropoietin The whole complex of macula densa and JG cells or granular cells is called JG-complex 1/11/2025 41 1/11/2025 42  Juxtaglomerular Apparatus (JGA) 1/11/2025 43 GFR regulation : Adjusting blood flow GFR is regulated by three mechanisms 1. Renal Autoregulation 2. Neural regulation 3. Hormonal regulation All three mechanism adjust; ü Renal blood pressure & resulting blood flow 1/11/2025 44  Autoregulation of GFR When the GFR is increased: – tubular fluid will pass with minimum reabsorption of the required substances. When the GFR is decreased: – tubular fluid will pass with maximum reabsorption of unwanted substances. Therefore, the glomerular filtrate must flow into the tubular system at an appropriate rate to: - allow unwanted substances to pass into the urine - reabsorb nutritionally important substances GFR shows only little change with a broad change in ABP b/n 80 – 220 mm Hg. 1/11/2025 45  Autoregulation of GFR … There are two autoregulation mechanisms of GFR 1. Afferent arteriole vasodilator feedback mechanism ↓GFR →Tubular fluid flows slowly →↑Na+, Cl- reabsorption →Detected by the macula densa, secret PG-E 1 & E 2 →Dilation of AA → ↑GFR 2. Efferent arteriole vasoconstrictor Feed.b mechanism ↓GFR →Tubular fluid flows slowly →↑Na+, Cl- reabsorption →Detected by the macula densa, secret PG-E 1 & E 2 →Stimulate JG-cel ls to secret renin → ↑Ang-II → vasoconstriction of EA → ↑GFR 1/11/2025 46  Neural regulation of GFR Sympathetic nerve fibers innervate afferent and efferent arteriole ü Sympathetic stimulation is low but can increase during hemorrhage and exercise ü Sympathetic stimulation constricts AA and ↓GFR Vasoconstriction occurs as a result which Ø Conserves blood volume (hemorrhage) and Ø Permits greater blood flow to other body parts (exercise) 1/11/2025 47  Hormonal regulation of GFR q Several hormones contribute to GFR regulation 1. Angiotensin II produced by renin (released by JG-cells) is a potent vasoconstrictor. ↓ GFR. 2. ANP released by atria when stretched, ↑ GFR by increasing capillary surface area available for filtration. 3. NO: a potent vasodilator, ↑ GFR 4. Endothelin: a potent vasoconstrictor, ↓ GFR 5. Prostaglandin E2 a potent vasodilator on AA, ↑ GFR 1/11/2025 48  Regulation of renin-angiotensin system 1/11/2025 49 Renin Release  Tubular reabsorption & secretions q Proximal convoluted tubule (PCT) - Composed of cuboidal cells with numerous microvilli and mitochondria. [15 mm long & 55 µm in diameter]. - Reabsorbs water and solutes from filtrate and secretes substances into it. q Loop of Henle – a hairpin-shaped loop of the renal tubule (U-shaped tubules), lie b/n PCT and DCT , has descending & ascending limbs with 2 segments: thin & thick segments q Distal convoluted tubule (DCT) – Cuboidal cells without microvilli that function more in secretion than reabsorption. 5 mm long, 35 µm in diameter. 1/11/2025 51 Tubular reabsorption & secretions… 1/11/2025 53  Function of proximal tubules 1. Reabsorption of nutrients. 2. Reabsorption of Na+ (70-75%). 3. Almost total reabsorption of K+. Fluid in the Loop of Henle is free of K+. K+ is secreted in the DT. 4. Passive reabsorption of Cl-, HCO3- Obligatory reabsorption of H2O (70-75%) along with Na, K, Cl, HCO3 independent of ADH. 5. Reabsorption of urea. 6. Secretion of H+, NH4, creatinin sulphate and drug metabolites. 1/11/2025 54  Function of proximal tubules… 1/11/2025 55  Glucose reabsorption in the PCT ü Glucose is reabsorbed along with Na+ in the early portion of the proximal tubule. üGlucose is typical of substances removed from the urine by secondary active transport. üEssentially all of the glucose is reabsorbed, and no more than a few milligrams appear in the urine per 24 hours. 1/11/2025 56  Na+ reabsorption in the PCT Paracellular transport of Trans-cellular transport of Na+ involves: Na+ involves: – Passage of Na+ through – Antiport carriers the tight junction b/n Na-H ATPase, Na-K ATPase cells – Symport carriers – Passive diffusion of Na+ Na-Glu, Na-aa, Na-HCO3- through Na-channels Transcellular Pathway Lumen Cells Plasma - Active/carrier mediated Paracellular Transport - Passive transport 1/11/2025 57  Na+ reabsorption in the PCT… 1/11/2025 58  Secondary active transport Tubular Interstitial Tubular Interstitial lumen Tubular Cell Fluid lumen Tubular Cell Fluid Co-transport Counter-transport (symport) (antiport) out in out in Na+ Na+ glucose H+ Co-transporters will move one Counter-transporters will move moiety, e.g. glucose, in the one moiety, e.g. H+, in the same direction as the Na+. opposite direction to the Na+. Tubular reabsorption & secretion (cont’d) q Loop of Henle Descending limb passive reabsorption of H2O Ascending limb active reabsorption of NaCl impermeable to H2O q Distal tubules (diluting segment) active reabsorption of NaCl impermeable to H2O & urea late DT is permeable is to H2O ADH dependently q Collecting ducts reabsorption of Na, Ca and H2O hormone dependently 1/11/2025 60  Tubular transport maximum (Tm) The maximum amount of substance (mg) transported (reabsorbed/secreted) by tubules per minutes. TmG (Tmax of glucose =350 mg/min) – the maximum amount of glucose in mg that can be reabsorbed by the renal tubules per minute it means glucose that is filtered in the glomerulus is reabsorbed. Determination of TmG is used as a renal function test – b/c it measures the reabsorptive power of the kidneys. 1/11/2025 61  Tubular transport maximum (Tm)… Renal threshold for glucose is 180 mg/dl – When BGC > 180 mg/dl, small amount start to be appeared in urine – When the TLoad of glucose is 400 mg/min, the amount excreted in urine is 400-350=50 mg/min. Tm for creatinin is 16 mg/min TmPAHA = 80 mg/min 1/11/2025 62  Tubular load (TLoad) of substances The rate of a particular substance filtered through the glomeruli into the tubules per minute It equals GFR times the concentration of the substance in the filtrate. TLoad of a subs (freely filtered) = Conc. In the filtrate X GFR TLoad of Glucose = 100 mg/dl X 125 ml/min = 125 mg/min TLoad of Na+ = 142 meq/1000 ml X 125 ml/min=18 meq/min TLoad of Cl- = 13 meq/min TLoad of Urea = 33 mg/min 1/11/2025 63  Renal plasma clearance A measure of the volume of plasma that is completely cleared of a given substance per minute. A measure of the efficiency of the kidneys with which the plasma is cleared of a given substance It is the ratio of the renal excretion rate of the substance to its concentration in plasma It can be calculated using the following formula: Cx = ____ Ux V Px Where: Cx = Clearance of the subs (ml/min) Ux = Concent. Of the subs. In urine (mg/ml) V = Volume of UO (ml/min) Px = Concent. of the subs in plasma (mg/ml) 1/11/2025 64  Importance of renal plasma clearance 1. Measurement of GFR GFR can be determined by inulin clearance test. The plasma clearance value of inulin (Cin) = GFR Inulin is a fructose polysaccharide, freely filtered in the glomerulus, neither reabsorbed nor secreted by the renal tubules 2. Measurement of RBF and RPF RBF/RPF is measured by PAHA, completely cleared 3. Indicator of the renal handling of different substances - reabsorption or secretion in the renal tubules Examples: Plasma clearance of glucose = 0 , Inulin= 125 ml/min, GFR Urea < GFR, partially reabsorbed Cx > GFR, Partially secreted 4. Gives quantitative information about renal diseases 1/11/2025 65  Function of Loop of Henle in the process of urine formation Create & maintain osmotic gradient in the renal medullary interstitium It involves in the formation of concentrated urine up to 1200 Mosm/l It acts as a counter-current multiplier system which creates Ø osmotic gradient in the renal medullary interstitium as well as in the tubule. 1/11/2025 66  Function of Loop of Henle… q A counter-current system is any system where there are two currents flowing parallel, opposite and adjacent to each other. q Counter-current multiplier operates actively to create an osmotic or chemical gradient in the renal interstitial space by the Loop of Henle and vasa recta q Counter-current exchanger operates passively to maintain an osmotic or chemical gradient 1/11/2025 67  Countercurrent system The U-shaped loop forms the counter-current system, which means fluid passes in opposite direction through 2 loops, Loop of Henle and vasa recta It has also a counter- current multiplier function, b/c it acts to increase (multiply) the osmolality of fluid in the loop of Henle as well as in the medullary interstitium. 1/11/2025 68  Counter-current multiplier system… v Osmolality of tubular fluid & interstitial fluid increases progressively as we go deep into the renal medulla from the cortex. v Formation of multiple stratification of osmolality by the flow of fluid in opposite directions in the LH and in VR. 1/11/2025 69  Countercurrent Mechanism… q Descending limb of Loop of Henle Permeable to water, but impermeable to Na+, K+, Cl-, urea Water flows out down the osmotic gradient Osmolality of tubular fluid increases progressively up to 1200 mosm/L q Thick segment of the ascending limb of Loop of Henle Impermeable to water & urea, but active reabsorption of electrolytes (Na+, Cl- and K+) The osmolaltiy of tubular fluid is progressively decreases up to 150 mosm/l 1/11/2025 70 1/11/2025 71 1/11/2025 72  Countercurrent system Function of vasa recta as a counter current exchanger maintains hyper-osmolarity of medullary interstitium through: a. Uptake of NaCl & urea & removal of water from the descending limb b. Removal of NaCl & urea & uptake of water in the ascending limb c. Slaggish flow of blood in it 1/11/2025 73 Hyperosmotic Gradient in the Renal Medulla Interstitium q Causes of hyperosmolality in the medullary interstitium 1. Counter-current arrangement of the ascending & descending limb of the LH 2. Both passive & active reabsorption of Na, Cl & K in the ascending limb of LH 3. Active reabsorption of Na+ and passive reabsorption of urea from CD q Importance of medullary hyperosmolarity It is essential for the formation of concentrated urine. This is b/c it leads to passive reabsorption of water from the CD (ADH). 1/11/2025 74 Formation of concentrated and diluted urine Importance: 1. When there is excess water in the body and body fluid osmolarity is reduced: v the kidney can excrete urine with an osmolarity as low as 50 mOsm/liter, v a concentration that is only about 1/6 the osmolarity of normal extracellular fluid. 2. Conversely, when there is a deficient of water and extracellular fluids osmolarity is high: v the kidney can excrete urine with a concentration of about 1200 to 1400 mOsm/liter. 1/11/2025 75  The basic requirements for formation of concentrated or diluted urine 1. Controlled secretion of antidiuretic hormone (ADH) which regulates the permeability of the distal tubules and collecting ducts to water 2. High osmolarity of the renal medullary interstitial fluid which provides the osmotic gradient necessary for water reabsorption to occur in the presence of high level of ADH. 1/11/2025 76  Water reabsorption Facultative (selective) Obligatory water reabsorption water reabsorption Using sodium & other solutes. Occurs mostly in Water follows solute to the collecting ducts interstitial fluid (transcellular Through the water and paracellular pathway). poles (channel) Largely influenced by sodium Regulated by the reabsorption ADH 1/11/2025 77  The Role of ADH There is a high osmolarity of the renal medullary interstitial fluid, which provides the osmotic gradient necessary for water reabsorption to occur. Reabsorption of water in the DT & CT is determined by the hormone ADH. Osmoreceptors in the hypothalamus detect the low levels of water (high osmolarity), so the hypothalamus sends an impulse to the pituitary gland which releases ADH into the bloodstream. ADH makes the wall of the DT and CT more permeable to water. Therefore, when ADH is present more water is reabsorbed and high amount of electrolytes are excreted. 1/11/2025 78  Formation of Water Pores: Mechanism of Vasopressin Action 1/11/2025 79  Mechanism of formation of concentrated urine When there is a shortage of H2O in the body ↓ECF volume, ↑Osmolality Stimulates osmoreceptors in the HT ↑ADH secretion ADH ↑ H2O reabsorption in the DT & CD ↑Excrition of solutes Concentrated (1200 mosm/l), in small volume of urine is produced 1/11/2025 80  Mechanism of formation of diluted urine When there is excess H2O in the body ↑ECF vlume, ↓Osmolality ↑Aldosterone secretion ↓ADH secretion ↑NaCl reabsorption in the DT & CD ↑H2O excretion 1/11/2025 Diluted urine (50-100 mosm/l) 81  The Effects of ADH on the distal collecting duct and Collecting Ducts 1/11/2025 82  Water handling of the renal tubules 1/11/2025 83 Tubular reabsorption of H2O and electrolyte 1. Reabsorption of H2O in the DT and CD is dependent on the presence of ADH 2. Reabsorption of Na+ in the DT and CD is dependent on aldosterone 3. Reabsorption of Ca2+ in the DT and CD is dependent on the presence of PTH and calcitriol 1/11/2025 84  Regulation of [Na+] and osmolality ↑[Na+] and ↑Osmolality ↓[Na+] or ↓Osmolality & ↑[K+] Stimulates osmoreceptors in the SON of HT Stimulates adrenal cortex ↑ADH secretion ↑Aldosterone secretion ↑H2O reabsorption in the ↑Na+ reabsorption DT and CD ↑K+ excretion in DT and CD ↓[Na+] and ↓Osmolality ↑[Na+] &↑Osmolality ↓[K+] back to normal back to normal  Diuretics Drugs that increase the urine output. Of 3 classes 1. Drugs increasing solute excretion a. Na+ reabsorption inhibitors Mercurials, thiazides, frusemide b. Na-H pump inhibitors: acetazolamide, NH4Cl c. Osmotic diuretics: mannitol, dextran, glucose 2. Drugs increasing GFR - cardiac glycosides, plasma expanders , xanthenes derivatives 3. Drug inhibiting release of ADH - water, ethanol alcohol 1/11/2025 86  Normal urine & blood values Urine pH ~ 6.0 Blood pH = 7.4 Blood [HCO3-] = 24 mM Blood PCO2 = 40 mmHg Plasma osmolality = 300 mOsm/kg water Urine osmolality = 600 mOsm/kg water – depends upon hydration status – note that this can vary between 50-1200 depending on water intake etc. 1/11/2025 87  Physical Characteristics of Urine Color and transparency – Clear, pale to deep yellow Concentrated urine has a deeper yellow color – Drugs, vitamin supplements, & diet can change the color – Cloudy urine may indicate infection of the urinary tract Odor – Fresh urine is slightly aromatic – Standing urine develops an ammonia odor – Some drugs and vegetables alter the usual odor pH – Slightly acidic (pH = 6) with a range of 4.5 to 8.0 – Diet can alter pH Specific gravity – Ranges from 1.001 to 1.035 – Is dependent on solute concentration 1/11/2025 88  Chemical Composition of Urine Urine is 95% water and 5% solutes Nitrogenous wastes include: - urea, uric acid, and creatinine Other normal solutes include: – Sodium, potassium, phosphate, and sulfate ions – Calcium, magnesium, and bicarbonate ions Abnormally high concentrations of any urinary constituents may indicate pathology. 1/11/2025 89 1/11/2025 90 1/11/2025 91  Ureters Slender tubes that convey urine from the kidneys to the bladder. Enter the base of the bladder through posterior wall – As bladder pressure increased (increased urine volume in bladder) distal ends of ureters are closed off & prevent backflow of urine into ureters Ureters have a trilayered wall – Epithelial mucosa – Smooth muscle – Fibrous connective tissue Ureters actively propel urine to the bladder via response to smooth muscle stretch. 1/11/2025 92  Urinary Bladder Smooth muscular sac that temporarily stores urine. It lies on the pelvic floor posterior to the pubic symphysis. v Males – prostate gland surrounds the neck inferiorly v Females – anterior to the vagina and uterus Trigone – triangular area outlined by the openings for the ureters & the urethra. Clinically important because infections tend to persist in this region. The bladder wall has 3 layers; epithelium, a thick muscular layer (detrusor muscle), a fibrous layer. It is distensible and collapses when empty. Accommodates as high as 1.5 L of urine. 1/11/2025 93  Urinary Bladder… 1/11/2025 94  Urethra Muscular tube that drains urine from the bladder & moves urine out of the body Sphincters keep the urethra closed when urine is not being passed Ø Internal sphincter – involuntary sphincter at the bladder-urethra junction Ø External sphincter – voluntary sphincter surrounding the urethra as it passes through the urogenital diaphragm Levator ani muscle – voluntary urethral sphincter 1/11/2025 95  Urethra … The female urethra is tightly bound to the anterior vaginal wall. – Its external opening lies anterior to the vaginal opening and posterior to the clitoris The male urethra has three named regions § Prostatic urethra – runs within the prostate gland § Membranous urethra – runs through the urogenital diaphragm § Spongy (penile) urethra – passes through the penis and opens via the external urethral orifice 1/11/2025 96  Micturition reflex 1. Stimulation of stretch receptors by large volume of urine (200- 400 ml) 2. Sensory impulse transmitted to the spinal cord through PNS 3. Motor impulse stimulates smooth muscle lining bladder & 4. Relax internal urethral sphincter (IUS) 5. Stretch receptors also send impulse to higher centers (Pons, HT and cerebral cortex) 6. Motor impulse from higher centers promote readiness to urinate 7. Identify places for urination 8. Relax external urethral sphincter 1/11/2025 97  Regulation of acid-base balance Normal blood pH: 7.35 – 7.45 - pH < 7.35 is called acidosis, >7.45 is called alkalosis - Acidosis & alkalosis disturb the function of cells, hormones, enzymes. The body has 5 pH regulatory mechanisms that control the normal range: 1. The chemical buffer system: has 3 components – Bicarbonate system: H2CO3 & NaHCO3 – Phosphate buffer system: NaH2PO4/Na2HPO4 – Hb & protein buffer system that can trap H+ or OH- 1/11/2025 98  Regulation of acid-base balance… 2. The respiratory buffer system: – Regulates pH by controlling PCO2 3. The renal buffer system: – Regulates pH by controlling the concentration of HCO3- and H+ – The kidneys regulate the concentration of H in the blood by excreting a variable amount of H in the urine. – They also conserve blood bicarbonate ions (HCO3), an important buffer of H. – Both activities help regulate blood pH. 1/11/2025 99  Pathopysiology of kidneys q Renal failer Ø a decrease or cessation of glomerular filtration Acute renal failure Chronic renal failure q Renal stone/ calculi – Nephrolithiasis/ Kidney stone/Urolithiasis q Glomerulonephritis q Nocturnal enuresis q Urinary tract infections 1/11/2025 100  Acute Renal Failure Pathophysiology v Prerenal Acute Renal Failure Dysfunction before the level of kidneys –Most common and most easily reversible v Renal Acute Renal Failure Dysfunction within the kidneys themselves v Postrenal Acute Renal Failure Dysfunction distal to the kidneys 1/11/2025 101  Acute Renal Failure … 1/11/2025 102  Chronic Renal Failure Chronic Renal Failure – Permanent Loss of Nephrons – End-Stage Renal Failure, 90% of the nephrons have been lost. Pathophysiology – Similar to Renal ARF Microangiopathy Glomerular injury Tubular cell injury Interstitial injury 1/11/2025 103  Renal Stone/Calculi Pathophysiology – Results when “too much insoluble stuff” accumulates in the kidneys. – Stone types: Calcium salts Struvite stones Uric acid Cystine 1/11/2025 104 Nephrolithiasis/Kidney stone/Urolithiasis - Crystalline structures made up of renal excreta in urine. - Mechanism of renal stone formation; 3 theories 1. The saturation theory: - ↑Stone components. e.g. Ca salt 2. The inhibitor deficiency theory: - ↓Inhibitor components 3. The matrix theory: - organic materials produced by renal epithelial cells serve as a nucleus for the formation of renal stone. 1/11/2025 105  Nephrolithiasis… q Types of kidney stone: 1. Ca-stone (Ca-oxalate, Ca-phosphate): - Causes: hypercalcemia, ↑↑PTH, Vit-D over dose 2. Magnisium ammonium phosphate stone (Struvite stone) - Cause: UTI 3. Uric acid stone - Causes: ↑Urine acidity (pH 5.5), Gout due to high protein diet 4. Cyctine stone - Cause: Cyctinurea due to genetic defect in aa metabolism 1/11/2025 106  Glomerulonephritis An inflammation of the glomeruli of the kidney. One of the most common causes is an allergic reaction to the toxins produced by streptococcal bacteria that have recently infected another part of the body, especially the throat. Because inflamed & swollen glomeruli allow blood cells & plasma proteins to enter the filtrate, – the urine contains many red blood cells (hematuria) & large amounts of protein. 1/11/2025 107  Urinary Incontinence Lack of voluntary control over micturition. Under about 2–3 years of age, urinary incontinence is normal because neurons to the external urethral sphincter muscle are not completely developed. Infants void whenever the urinary bladder is sufficiently distended to trigger the reflex. In stress incontinence, the most common type of urinary incontinence, physical stresses that increase abdominal pressure, such as coughing, sneezing, laughing, exercising, straining, lifting heavy objects, pregnancy, or simply walking, cause leakage of urine from the urinary bladder. 1/11/2025 108  Nocturnal enuresis Discharge of urine during sleep, resulting in bed-wetting. Occurs in about 15% of 5-year-old children and generally resolves spontaneously, afflicting only about 1% of adults. Possible causes include: – smaller-than-normal urinary bladder capacity – failure to awaken in response to a full urinary bladder – above-normal production of urine at night (nocturia). 1/11/2025 109  Urinary tract infections (UTIs) The most common bacterial infections and the second most common illness (after colds) among women. About 10–15% of women develop UTIs several times a month. Men get UTIs, too, but much less frequently. The female’s shorter urethra allows bacteria to enter the urinary bladder more easily. In addition, the urethral and anal openings are closer in females. Most first-time UTIs are caused by Escherichia coli (E. coli) bacteria that have migrated to the urethra from the anal area. 1/11/2025 110  Urinary tract infections… E. coli bacteria are necessary for proper digestion and are welcome in the intestinal tract, but they cause much pain and suffering if they infect the urinary system. Personal hygiene is the first line of prevention. Care must be taken to avoid transporting bacteria from the anal area to the urethra. Girls should be taught to wipe from front to back and to wash hands thoroughly after using the toilet. When bathing, women and girls should wash from front to back as well. 1/11/2025 111 1/11/2025 112 1/11/2025 113