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HUMAN PHYSIOLOGY PDF.pdf

The document provides information on renal physiology and kidney function. It discusses the structure and functions of the kidneys, including regulating blood volume, wastes, electrolytes and pH. It describes the gross structure of the urinary system and microscopic kidney structure, focusing on the nephron as the functional unit. Key concepts covered include glomerular filtration, reabsorption of salt and water in the proximal tubule and nephron loop, and the countercurrent multiplier system for concentration gradients.

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©McGraw-Hill Education RENAL PHYSIOLOGY PRESENTED BY N. G. AKUNGA BPHARM, MSc
© 2019 McGraw-Hill Education 2 I. Structure and Function of the Kidneys
© 2019 McGraw-Hill Education 3 A. Kidney Functions 1. Regulation of the extracellular fluid environment in the body, including: a. Volume of blood plasma (affects blood pressure) b. Wastes c. Electrolytes d. pH e. Secrete erythropoietin
© 2019 McGraw-Hill Education 4 B. Gross Structure of the Urinary System (1) 1. Introduction a. Urine made in the kidney nephrons drains into the renal pelvis, then down the ureter to the urinary bladder. b. It passes from the bladder through the urethra to exit the body. c. Urine is transported using peristalsis.
© 2019 McGraw-Hill Education 5 Organs of the Urinary System
© 2019 McGraw-Hill Education 6 Gross Structure of the Urinary System (2) 2. Kidney Structure a. The kidney has two distinct regions: 1) Renal cortex 2) Renal medulla, made up of renal pyramids and columns b. Each pyramid drains into a minor calyx → major calyx → renal pelvis.
© 2019 McGraw-Hill Education 7 Kidney Structure (1)
© 2019 McGraw-Hill Education 8 Radiograph of the Urinary System © SPL/Science Source
© 2019 McGraw-Hill Education 9 Kidney Stones (1) 1. Nephrolithiasis or kidney stones, are hard objects formed in the kidneys containing crystallized minerals or waste products. 2. About 80% are calcium stones but others can be of magnesium ammonium phosphate or uric acid. 3. The tendency to form stones is increased if a person is dehydrated. 4. Large stones in the calyces or pelvis may obstruct urine flow, and smaller stones (usually less than 5 mm) that pass into a ureter can produce intense pain.
© 2019 McGraw-Hill Education 10 Kidney Stones (2) 5. Treatment options are: a. Medications are available to help pass kidney stones b. Lithotripsy (shock waves are used to shatter it) c. Surgery
© 2019 McGraw-Hill Education 11 C. Control of Micturition (1) 1. Detrusor muscles line the wall of the urinary bladder. a. Gap junctions connect smooth muscle cells. b. Innervated by parasympathetic neurons, which release acetylcholine onto muscarinic ACh receptors 2. Sphincters surround urethra. a. Internal urethral sphincter: smooth muscle b. External urethral sphincter: skeletal muscle
© 2019 McGraw-Hill Education 12 Control of Micturition (2) 3. Stretch receptors in the bladder send information to S2−S4 regions of the spinal cord. a. These neurons normally inhibit parasympathetic nerves to the detrusor muscles, while somatic motor neurons to the external urethral sphincter are stimulated. b. Called the guarding reflex c. Prevents involuntary emptying of bladder
© 2019 McGraw-Hill Education 13 Control of Micturition (3) 4. Stretch of the bladder initiates the voiding reflex. a. Information about stretch passes up the spinal cord to the micturition center of the pons. b. Parasympathetic neurons cause detrusor muscles to contract rhythmically c. Inhibition of sympathetic innervation of the internal urethral sphincter causes it to relax. d. Person feels the need to urinate and can control when with external urethral sphincter.
© 2019 McGraw-Hill Education 14 Urinary Incontinence 1. Urinary incontinence is uncontrolled urination due to loss of bladder control and has many possible causes. 2. Stress urinary incontinence is present when urine leakage occurs due to increased abdominal pressure, as during sneezing, coughing, and laughing. 3. This happens in women when the pelvic floor no longer provides adequate support to the urethra due to childbirth or aging. It is often treated by a sling surgery, in which inserted mesh provides additional support for the urethra. 4. In men, urinary incontinence frequently occurs as a result of treatments for prostate cancer.
© 2019 McGraw-Hill Education 15 Overactive Bladder 1. Overactive bladder involves uncontrolled contractions of the detrusor muscle that produce a great urge to urinate and the leakage of a large volume of urine. 2. This urgency is a hallmark of a person with an overactive bladder, who also usually experiences frequent urinations and other symptoms. 3. Urinary incontinence can be diagnosed by urodynamic testing and includes cystometric tests, in which bladder pressure and compliance (dispensability) are measured as the bladder is filled with warm water and the subject is asked to say when the urge to urinate appears.
© 2019 McGraw-Hill Education 16 D. Microscopic Kidney Structure (1) 1. Nephron: functional unit of the kidney a. Each kidney has more than a million nephrons. b. Nephron consists of small tubules and associated blood vessels. c. Blood is filtered, fluid enters the tubules, is modified, then leaves the tubules as urine
© 2019 McGraw-Hill Education 17 Kidney Structure (2)
© 2019 McGraw-Hill Education 18 Renal Blood Vessels Renal artery → Interlobar arteries → Arcuate arteries → Interlobular arteries → Afferent arterioles Glomerulus → Efferent arterioles → Peritubular capillaries → Interlobular veins → Arcuate veins → Interlobar veins → Renal vein
© 2019 McGraw-Hill Education 19 Microscopic Kidney Structure (2) 2. Nephron Tubules a. Glomerular (Bowman’s) capsule surrounds the glomerulus. Together, they make up the renal corpuscle. b. Filtrate produced in renal corpuscle passes into the proximal convoluted tubule.
© 2019 McGraw-Hill Education 20 Microscopic Kidney Structure (3) Nephron Tubules, Continued c. Next, fluid passes into the descending and ascending limbs of the loop of Henle. d. After the loop of Henle, fluid passes into the distal convoluted tubule. e. Finally, fluid passes into the collecting duct. f. The fluid is now urine and will drain into a minor calyx.
© 2019 McGraw-Hill Education 21 Nephron Tubules & Associated Blood Vessels
© 2019 McGraw-Hill Education 22 Microscopic Kidney Structure (4) 4. Two Types of Nephrons a. Juxtamedullary: better at making concentrated urine b. Cortical
© 2019 McGraw-Hill Education 23 Polycystic Kidney Disease (PKD) 1. PKD is a congenital disorder in which the kidneys are enlarged by hundreds to thousands of fluid-filled cysts that form in all segments of the nephron and eventually separate from the tubules. 2. Autosomal dominant polycystic kidney disease accounts for most cases and affects almost 1 in 1,000 people. 3. The gene responsible for 85% of ADPKD is located on chromosome 16 and codes for a protein called polycystin- 1,whereas a gene located on chromosome 4 that codes for polycystin-2 is responsible for the other cases. 4. There is no cure presently available, only treatments for the complications of this disease.
© 2019 McGraw-Hill Education 24 II. Glomerular Filtration
© 2019 McGraw-Hill Education 25 A. Glomerular Corpuscle (1) 1. Capillaries of the glomerulus are fenestrated. a. Large pores allow water and solutes to leave but not blood cells and plasma proteins. 2. Fluid entering the glomerular capsule is called filtrate
© 2019 McGraw-Hill Education 26 Glomerular Corpuscle (2) 3. Filtrates must pass through: a. Capillary fenestrae b. Glomerular basement membrane c. Visceral layer of the glomerular capsule composed of cells called podocytes with extensions called pedicles
© 2019 McGraw-Hill Education 27 Glomerular Capillaries & Capsule © Professor P.M. Motta and M. Sastellucci/SPL/Science Source
© 2019 McGraw-Hill Education 28 Glomerular Corpuscle & Filtration Barrier © SPL/Science Source
© 2019 McGraw-Hill Education 29 Glomerular Corpuscle (3) d. Slits in the pedicles called slit diaphragm pores are the major barrier for the filtration of plasma proteins. 1) Defect here causes proteinuria = proteins in urine. 2) Some albumin is filtered out but is reabsorbed by active endocytosis.
© 2019 McGraw-Hill Education 30 B. Glomerular Ultrafiltrate (1) 1. Fluid in glomerular capsule gets there via hydrostatic pressure of the blood, colloid osmotic pressure, and very permeable capillaries. 2. These forces produce a net filtration pressure of about 10mmHg
© 2019 McGraw-Hill Education 31 Formation of Glomerular Ultrafiltrate
© 2019 McGraw-Hill Education 32 Glomerular Ultrafiltrate (2) 3. Filtration Rates a. Glomerular filtration rate (GFR): volume of filtrate produced by both kidneys each minute = 115 to 125 ml. 1) 180 L/day (~45 gal) 2) Total blood volume is filtered every 40 minutes 3) Most must be reabsorbed immediately
© 2019 McGraw-Hill Education 33 C. Regulation of Glomerular Filtration Rate (1) 1. Vasoconstriction or dilation of afferent arterioles changes filtration rate. a. Extrinsic regulation via sympathetic nervous system b. Intrinsic regulation via signals from the kidneys; called renal autoregulation
© 2019 McGraw-Hill Education 34 Regulation of Glomerular Filtration Rate (2) 2. Sympathetic Nerve Effects a. In a fight/flight reaction, there is vasoconstriction of the afferent arterioles. b. Helps divert blood to heart and muscles c. Urine formation decreases to compensate for the drop in blood pressure
© 2019 McGraw-Hill Education 35 Sympathetic Nerve Effects
© 2019 McGraw-Hill Education 36 Regulation of Glomerular Filtration Rate (3) 3. Renal Autoregulation a. GFR is maintained at a constant level even when blood pressure (BP) fluctuates greatly. 1) Afferent arterioles dilate if BP < 70. 2) Afferent arterioles constrict if BP > normal. b. Myogenic constriction: Smooth muscles in arterioles sense an increase in blood pressure.
© 2019 McGraw-Hill Education 37 Regulation of Glomerular Filtration Rate (4) Renal Autoregulation, Continued c. Tubuloglomerular feedback: Cells in the ascending limb of the loop of Henle called macula densa sense a rise in water and sodium as occurs with increased blood pressure (and filtration rate). 1) They send a chemical signal (ATP) to constrict the afferent arterioles.
© 2019 McGraw-Hill Education 38 Regulation of Glomerular Filtration Rate (5) TABLE 17.1 | Regulation of the Glomerular Filtration Rate (GFR) Regulation Stimulus Afferent Arteriole GFR Sympathetic nerves Activation by baroreceptor reflex or by higher brain centers Constricts Decreases Autoregulation Decreased blood pressure Dilates No change Autoregulation Increased blood pressure Constricts No change
© 2019 McGraw-Hill Education 39 III. Reabsorption of Salt and Water
© 2019 McGraw-Hill Education 40 A. Introduction: Reabsorption 1. Reabsorption – return of filtered molecules to the blood 2. 180 L of water is filtered per day, but only 1 to 2 L is excreted as urine. a. This will increase when well hydrated and decrease when dehydrated. b. A minimum 400 ml must be excreted to rid the body of wastes = obligatory water loss. c. 85% of reabsorption occurs in the proximal tubules and descending loop of Henle. This portion is unregulated.
© 2019 McGraw-Hill Education 41 Filtration and Reabsorption
© 2019 McGraw-Hill Education 42 B. Reabsorption in the Proximal Tubule (1) 1. The osmolality of filtrate in the glomerular capsule is equal to that of blood plasma (isoosmotic). 2. Na+ is actively transported out of the filtrate into the peritubular blood to set up a concentration gradient to drive osmosis.
© 2019 McGraw-Hill Education 43 Reabsorption in the Proximal Tubule (2) 3. Active Transport a. Cells of the proximal tubules are joined by tight junctions on the apical side (facing inside the tubule). b. The apical side also contains microvilli. c. These cells have a lower Na+ concentration than the filtrate inside the tubule due to Na+/K+ pumps on the basal side of the cells and low permeability to Na+. d. Na+ from the filtrate diffuses into these cells and is then pumped out the other side.
© 2019 McGraw-Hill Education 44 Reabsorption in the Proximal Tubule (3) 4. Passive Transport a. The pumping of sodium into the interstitial space attracts negative Cl− out of the filtrate. b. Water then follows Na+ and Cl− into the tubular cells and the interstitial space. c. The ions and water diffuse into the peritubular capillaries.
© 2019 McGraw-Hill Education 45 Salt and Water Reabsorption in the Proximal Tubule
© 2019 McGraw-Hill Education 46 Reabsorption in the Proximal Tubule (4) 5. Significance of proximal tubule reabsorption a. 65% of the salt and water is reabsorbed, but that is still too much filtrate b. An additional 20% of water is reabsorbed through the descending limb of the Loop of Henle. 1) Happens continuously and is unregulated 2) The final 15% of water (~27 L) is absorbed later in the nephron under control of the hormone Anti-Diuretic Hormone (ADH). 3) Fluid entering loop of Henle is isotonic to extracellular fluids.
© 2019 McGraw-Hill Education 47 C. Countercurrent Multiplier System (1) 1. Water cannot be actively pumped out of the tubes, and it will not cross if isotonic to extracellular fluid. a. The structure of the loop of Henle allows for a concentration gradient to be set up for the osmosis of water. b. The ascending portion sets up this gradient.
© 2019 McGraw-Hill Education 48 Countercurrent Multiplier System (2) 2. Ascending Limb of the Loop of Henle a. Salt (NaCl) is actively pumped into the interstitial fluid from the thick segment of the limb 1) Movement of Na+ down its electrochemical gradient from filtrate into tubule cells powers the secondary active transport of Cl− and K+. 2) Na+ is moved into interstitial space via Na+/K+ pump. Cl− follows Na+ passively due to electrical attraction, and K+ passively diffuses back into filtrate.
© 2019 McGraw-Hill Education 49 Transport of Ions in the Ascending Limb of the Loop of Henle
© 2019 McGraw-Hill Education 50 Countercurrent Multiplier System (3) Ascending Limb of the Loop of Henle, Continued b. Walls are not permeable to water, so osmosis cannot occur from the ascending part of the loop. c. Surrounding interstitial fluid becomes increasingly solute concentrated at the bottom of the tube. d. Tubular fluid entering the descending loop of Henle becomes more hypotonic as it descends the loop.
© 2019 McGraw-Hill Education 51 Countercurrent Multiplier System (4) 3. Descending Limb of the Loop of Henle a. Is not permeable to salt but is permeable to water b. Water is drawn out of the filtrate and into the interstitial space where it is quickly picked up by capillaries. c. As it descends, the fluid becomes more solute concentrated. 1) This is perfect for salt transport out of the fluid in the ascending portion.
© 2019 McGraw-Hill Education 52 Countercurrent Multiplier System (5)
© 2019 McGraw-Hill Education 53 Countercurrent Multiplier System (6) 4. Countercurrent Multiplication a. Positive feedback mechanism is created between the two portions of the loop of Henle. 1) The more salt the ascending limb removes, the saltier the fluid entering it will be (due to loss of water in descending limb).
© 2019 McGraw-Hill Education 54 Countercurrent Multiplier System (7) b. Steps of countercurrent mechanism 1) Interstitial fluid is hypertonic due to NaCl pumped out of the ascending limb 2) Water leaves descending limb by osmosis, making the filtrate hypertonic going into the ascending limb 3) More NaCl in the ascending limb can now be pumped out into the interstitial fluid
© 2019 McGraw-Hill Education 55 Countercurrent Multiplier System (8) Steps of Countercurrent Mechanism, Continued 4) The greater concentration of the interstitial fluid draws more water from the descending limb 5) Filtrate in ascending limb now more concentrated 6) Continues until the maximum NaCl concentration of the inner medulla is reached.
© 2019 McGraw-Hill Education 56 Countercurrent Multiplier System (9) c. Vasa Recta 1) Specialized blood vessels around loop of Henle, which also have a descending and ascending portion 2) Help create the countercurrent system because they take in salts in the descending region but lose them again in the ascending region a) Keep salts in the interstitial space
© 2019 McGraw-Hill Education 57 Countercurrent Multiplier System (10) Vasa Recta, Continued 3) High salt concentration (oncotic pressure) at the beginning of the ascending region pulls in water, which is removed from the interstitial space. a) Also keeps salt concentration in the interstitial space high 4) There are also urea transporters and aquaporins to aid in the countercurrent exchanges
© 2019 McGraw-Hill Education 58 Countercurrent Exchange in the Vasa Recta
© 2019 McGraw-Hill Education 59 Countercurrent Multiplier System (11) Vasa Recta, Continued 5. Effects of Urea a. Urea is a waste product of protein metabolism b. Contributes to countercurrent system 1) Transported out of collecting duct and into interstitial fluid 2) Diffuses back into ascending limb and cycles around continuously 3) Helps set up solute concentration gradients
© 2019 McGraw-Hill Education 60 Role of Urea in Urine Concentration
© 2019 McGraw-Hill Education 61 Renal Tubule Transport Properties TABLE 17.2 Transport Properties of Different Segments of the Renal Tubules and the Collecting Ducts Passive Transport Nephron Segment Active Transport Salt Water Urea Proximal tubule Na+ Cl− Yes Yes Descending limb of the nephron loop None Maybe Yes No Thin segment of ascending limb None NaCl No Yes Thick segment of ascending limb Na+ Cl− No No Distal tubule Na+ Cl− No** No Collecting duct* Slight Na+ No Yes (ADH) or slight (no ADH) Yes *The permeability of the collecting duct to water depends on the presence of ADH. **The last part of the distal tubule, however, is permeable to water.
© 2019 McGraw-Hill Education 62 Renal Tubule Osmolality
© 2019 McGraw-Hill Education 63 D. Collecting Duct and ADH (1) 1. Last stop in urine formation 2. Impermeable to NaCl but permeable to water a. Also influenced by hypertonicity of interstitial space – water will leave via osmosis if able to b. Permeability to water depends on the number of aquaporin channels in the cells of the collecting duct c. Availability of aquaporins determined by ADH (antidiuretic hormone; arginine vasopressin)
© 2019 McGraw-Hill Education 64 Collecting Duct and ADH (2) 3. ADH binds to receptors on collecting duct cells → cAMP → Protein kinase → Vesicles with aquaporin channels fuse to plasma membrane. a) Water channels are removed without ADH. 4. ADH is produced by neurons in the hypothalamus but stored and released from the posterior pituitary gland a) Release stimulated by an increase in blood osmolality
© 2019 McGraw-Hill Education 65 ADH Stimulation of Aquaporin Channels
© 2019 McGraw-Hill Education 66 Homeostasis of Plasma Concentration by ADH
© 2019 McGraw-Hill Education 67 ADH Secretion and Action TABLE 17.3 Antidiuretic Hormone Secretion and Action Stimulus Receptors Secretion of ADH Effects on Urine Volume Effects on Blood ↑Osmolality (dehydration) Osmoreceptors in hypothalamus Increased Decreased Increased water retention; decreased blood osmolality ↓Osmolality Osmoreceptors in hypothalamus Decreased Increased Water loss increases blood osmolality ↑Blood volume Stretch receptors in left atrium Decreased Increased Decreased blood volume ↓Blood volume Stretch receptors in left atrium Increased Decreased Increased blood volume
© 2019 McGraw-Hill Education 68 Diabetes Insipidus (1) 1. Diabetes insipidus is characterized by polyuria (a large urine volume), thirst, and polydipsia (drinking a lot of fluids). The urine is dilute, with a hypotonic concentration of less than 300 mOsm. 2. There are two major types of diabetes insipidus: a. Central diabetes insipidus-inadequate secretion of ADH b. Nephrogenic diabetes insipidus- inability of the kidneys to respond to ADH. 3. Nephrogenic diabetes insipidus may be caused by genetic defects in either the aquaporin channels or the ADH receptors.
© 2019 McGraw-Hill Education 69 Diabetes Insipidus (2) 4. More commonly, it is acquired as a response to drug therapy (from lithium given to treat bipolar disorder) or other causes. 5. People with central diabetes insipidus can take desmopressin when needed, and those with nephrogenic diabetes insipidus must drink a lot of water to prevent dehydration.
© 2019 McGraw-Hill Education 70 IV. Renal Plasma Clearance
© 2019 McGraw-Hill Education 71 A. Transport Processes Affecting Renal Clearance (1) 1. Kidneys must also remove excess ions and wastes from the blood. a. Sometimes called renal clearance b. Filtration in the glomerular capsule begins this process. c. Reabsorption returns some substances to the blood (decreases renal clearance) d. Secretion finishes the process when substances are moved from the peritubular capillaries into the tubules. (increases renal clearance)
© 2019 McGraw-Hill Education 72 Transport Processes Affecting Renal Clearance (2) 2. Excretion Rate a. Excretion rate = (filtration rate + secretion rate) – reabsorption rate b. Used to measure glomerular filtration rate (GFR), an indicator of renal health
© 2019 McGraw-Hill Education 73 Secretion is the Reverse of Reabsorption
© 2019 McGraw-Hill Education 74 Transport Processes Affecting Renal Clearance (3) 3. Secretion of Drugs a. Membrane carriers specific to foreign substances transport them into the tubules. b. Called organic anion transporters (OATs) or organic cation transporters (OCTs) c. Carriers are polyspecific – overlap in function d. Very fast; may interfere with action of therapeutic drugs
© 2019 McGraw-Hill Education 75 B. Clearance of Inulin (1) 1. Inulin is a compound found in garlic, onion, dahlias, and artichokes. a. Great marker of glomerular filtration rate because it is filtered but not reabsorbed or secreted GFR = V × U P V = rate of urine formation U = inulin concentration in urine P = inulin concentration in plasma
© 2019 McGraw-Hill Education 76 Renal Clearance of Inulin
© 2019 McGraw-Hill Education 77 Clearance of Inulin (2) 2. Renal Plasma Clearance Calculation a. Volume of plasma from which a substance is completely removed by the kidneys in 1 minute 1) Inulin is filtered only. Clearance = GFR 2) Anything that can be reabsorbed has a clearance < GFR. 3) If a substance is filtered and secreted, it will have a clearance > GFR. 4) Renal plasma clearance uses same formula as GFR.
© 2019 McGraw-Hill Education 78 Clearance of Inulin (3) Renal Plasma Clearance Calculation, Continued b. Clearance of urea is less than GFR – means some is reabsorbed
© 2019 McGraw-Hill Education 79 Estimated GFR with Creatinine 1. Creatinine is produced in muscles from creatine and released into the blood plasma, where its concentration is used to help assess kidney function. 2. Creatinine is filtered in the kidneys and not reabsorbed, but it is slightly secreted by the tubules. 3. This gives it a renal plasma clearance a little greater than that of inulin (and thus a little greater than the true GFR). 4. However, its plasma concentration, together with a person’s age, sex, and weight, is frequently used in equations to calculate an estimated GFR (eGFR). 5. The ratio of the plasma concentrations of urea (called a BUN -blood urea nitrogen test) to creatinine provides additional information about kidney health.
© 2019 McGraw-Hill Education 80 Renal Plasma Clearance TABLE 17.4 Effects of Filtration, Reabsorption, and Secretion on Renal Plasma Clearance Term Definition Effect on Renal Clearance Filtration A substance enters the glomerular ultrafiltrate. Some or all of a filtered substance may enter the urine and be “cleared” from the blood. Reabsorption A substance is transported from the filtrate, through tubular cells, and into the blood. Reabsorption decreases the rate at which a substance is cleared; clearance rate is less than the glomerular filtration rate (GFR). Secretion A substance is transported from peritubular blood, through tubular cells, and into the filtrate. When a substance is secreted by the nephrons, its renal plasma clearance is greater than the GFR. TABLE 17.5 | Renal “Handling” of Different Molecules in the Blood Plasma If Substance Is: Example Concentration in Renal Vein Renal Clearance Rate Not filtered Proteins Same as in renal artery Zero Filtered, not reabsorbed or secreted Inulin Less than in renal artery Equal to GFR (115–125 ml/min) Filtered, partially reabsorbed Urea Less than in renal artery Less than GFR Filtered, completely reabsorbed Glucose Same as in renal artery Zero Filtered and secreted PAH Less than in renal artery; approaches zero Greater than GFR; up to total plasma flow rate (~625 ml/min) Filtered, reabsorbed, and secreted K+ Variable Variable
© 2019 McGraw-Hill Education 81 C. Clearance of PAH 1. Not all blood delivered to the glomeruli is filtered in each pass, so blood must make several passes to completely clear a substance. 2. PAH (para-aminohippuric acid) is an exogenous molecule injected for measurement of total renal blood flow. 3. Substances not filtered must be secreted into the tubules by active transport from the peritubular capillaries 4. All PAH in the peritubular capillaries will be secreted by OATs, so the time it takes to clear all PAH injected indicates blood flow to these capillaries.
© 2019 McGraw-Hill Education 82 Renal Clearance of PAH
© 2019 McGraw-Hill Education 83 D. Reabsorption of Glucose (1) 1. Glucose (and amino acids) is easily filtered out into the glomerular capsule 2. Completely reabsorbed in the proximal tubule via secondary active transport with sodium, facilitated diffusion, and simple diffusion
© 2019 McGraw-Hill Education 84 Mechanism of Reabsorption in the Proximal Tubule
© 2019 McGraw-Hill Education 85 Reabsorption of Glucose (2) 3. Glucose/Na+ cotransporters have a transport maximum (Tm). a. If there is too much glucose in the filtrate, it will not be completely reabsorbed because all the carriers are in use (saturated). b. Extra glucose spills over into the urine = glycosuria and is a sign of diabetes mellitus. c. Extra glucose in the blood also results in decreased water reabsorption and possible dehydration.
© 2019 McGraw-Hill Education 86 V. Renal Control of Electrolyte and Acid-Base Balance
© 2019 McGraw-Hill Education 87 A. Introduction: Renal Control of Electrolyte and Acid-Base Balance 1. Kidneys match electrolyte (Na+, K+, Cl−, bicarbonate, phosphate) excretion to ingestion. a. Control of Na+ levels is important in blood pressure and blood volume. b. Control of K+ levels is important in healthy skeletal and cardiac muscle activity. c. Aldosterone plays a big role in Na+ and K+ balance.
© 2019 McGraw-Hill Education 88 B. Role of Aldosterone in Na+/K+ Balance (1) 1. About 90% of filtered Na+ and K+ is reabsorbed early in the nephron. a. This is not regulated. 2. An assessment of what the body needs is made, and aldosterone controls additional reabsorption of Na+ and secretion of K+ in the distal tubule and collecting duct.
© 2019 McGraw-Hill Education 89 Role of Aldosterone in Na+/K+ Balance (2) 3. Potassium Secretion a. Aldosterone independent response: Increase in blood K+ triggers an increase in the number of K+ channels in the cortical collecting duct. 1) When blood K+ levels drop, these channels are removed. b. Aldosterone-dependent response: Increase in blood K+ triggers adrenal cortex to release aldosterone. 1) This increases K+ secretion in the distal tubule and collecting duct.
© 2019 McGraw-Hill Education 90 Potassium is Reabsorbed and Secreted
© 2019 McGraw-Hill Education 91 Role of Aldosterone in Na+/K+ Balance (3) Potassium Secretion, Continued c. Sodium and Potassium 1) Increases in sodium absorption drive extra potassium secretion. 2) Due to: a) Potential difference created by Na+ reabsorption driving K+ through K+ channels b) Stimulation of renin-angiotensin-aldosterone system by water and Na+ in filtrate c) Increased flow rates bend cilia on the cells of the distal tubule, resulting in activation of K+ channels
© 2019 McGraw-Hill Education 92 Role of Aldosterone in Na+/K+ Balance (4) Potassium Secretion, Continued 4. Control of Aldosterone Secretion a. A rise in blood K+ directly stimulates production of aldosterone in the adrenal cortex. b. A fall in blood Na+ indirectly stimulates production of aldosterone via the renin- angiotensin-aldosterone system.
© 2019 McGraw-Hill Education 93 C. Juxtaglomerular Apparatus (1) 1. Located where the afferent arteriole comes into contact with the distal tubule
© 2019 McGraw-Hill Education 94 Juxtaglomerular Apparatus (2) 2. A decrease in plasma Na+ results in a fall in blood volume. a. Sensed by juxtaglomerular apparatus b. Granular cells secrete renin into the afferent arteriole. c. This converts angiotensinogen into angiotensin I. d. Angiotensin-converting enzyme (ACE) converts this into angiotensin II.
© 2019 McGraw-Hill Education 95 Juxtaglomerular Apparatus (3) 3. Stimulates adrenal cortex to make aldosterone a. Promotes the reabsorption of Na+ from cortical collecting duct b. Promotes secretion of K+ c. Increases blood volume and raises blood pressure
© 2019 McGraw-Hill Education 96 Juxtaglomerular Apparatus (4) 4. Regulation of Renin Secretion a. Low salt levels result in lower blood volume due to inhibition of ADH secretion. 1) Less water is reabsorbed in collecting ducts and more is excreted in urine. b. Reduced blood volume is detected by granular cells that act as baroreceptors. They then secrete renin. 1) Granular cells are also stimulated by sympathetic innervation from the baroreceptor reflex.
© 2019 McGraw-Hill Education 97 Homeostasis of Plasma Na+
© 2019 McGraw-Hill Education 98 Juxtaglomerular Apparatus (5) 5. Macula Densa a. Part of the distal tubule that forms the juxtaglomerular apparatus b. Sensor for tubuloglomerular feedback needed for regulation of glomerular filtration rate 1) When there is more Na+ and H2O in the filtrate, a signal is sent to the afferent arteriole to constrict limiting filtration rate. 2) Controlled via negative feedback
© 2019 McGraw-Hill Education 99 Juxtaglomerular Apparatus (6) Macula Densa, Continued c. When there is more Na+ and H2O in the filtrate, a signal is sent to the afferent arteriole to inhibit the production of renin. 1) This results in less reabsorption of Na+, allowing more to be excreted. 2) This helps lower Na+ levels in the blood.
© 2019 McGraw-Hill Education 100 D. Atrial Natriuretic Peptide (1) 1. Increases in blood volume also increase the release of atrial natriuretic peptide hormone from the atria of the heart when atrial walls are stretched. 2. Stimulates kidneys to excrete more salt and therefore more water 3. Decreases blood volume and blood pressure
© 2019 McGraw-Hill Education 101 Atrial Natriuretic Peptide (2) 1. In addition to atrial natriuretic peptide (ANP), scientists have discovered a natriuretic hormone released by the heart’s ventricles called B-type natriuretic peptide (BNP). 2. BNP is secreted in response to increased volume and pressure within the ventricles, and it acts like ANP to promote diuresis. 3. The secretion of BNP increases in congestive heart failure (CHF) so measurements of the blood level of BNP are used clinically to help diagnose CHF.
© 2019 McGraw-Hill Education 102 Regulation of Renin and Aldosterone Secretion TABLE 17.6 Regulation of Renin and Aldosterone Secretion Stimulus Effect on Renin Secretion Angiotensin II Production Aldosterone Secretion Mechanisms ↓Blood volume Increased Increased Increased Low blood volume stimulates renal baroreceptors; granular cells release renin. ↑Blood volume Decreased Decreased Decreased Increased blood volume inhibits baroreceptors; increased Na+ in distal tubule acts via macula densa to inhibit release of renin from granular cells. ↑ K+ None Not changed Increased Direct stimulation of adrenal cortex ↑Sympathetic nerve activity Increased Increased Increased α-adrenergic effect stimulates constriction of afferent arterioles; β-adrenergic effect stimulates renin secretion directly.
© 2019 McGraw-Hill Education 103 E. Relationship Between Na+, K+, and H+ 1. Reabsorption of Na+ stimulates the secretion of other positive ions; K+ and H+ compete. 2. Acidosis stimulates the secretion of H+ and inhibits the secretion of K+ ions; acidosis can lead to hyperkalemia. 3. Alkalosis stimulates the secretion and excretion of more K+. 4. Hyperkalemia stimulates the secretion of K+ and inhibits secretion of H+; can lead to acidosis
© 2019 McGraw-Hill Education 104 Reabsorption of Na+ and Secretion of K+, and H+
© 2019 McGraw-Hill Education 105 F. Acid-Base Regulation (1) 1. Kidneys maintain blood pH by reabsorbing bicarbonate and secreting H+; urine is thus acidic. 2. Proximal tubule uses Na+/H+ pumps to exchange Na+ out and H+ in. a. Some of the H+ brought in is used for the reabsorption of bicarbonate. b. Antiport secondary active transport
© 2019 McGraw-Hill Education 106 Acid-Base Regulation (2) 3. Bicarbonate cannot cross the inner tubule membrane so must be converted to CO2 and H2O using carbonic anhydrase. a. Bicarbonate + H+ → carbonic acid b. Carbonic acid (w/ carbonic anhydrase) → H2O + CO2 c. CO2 can cross into tubule cells, where the reaction reverses and bicarbonate is made again. d. This diffuses into the interstitial space.
© 2019 McGraw-Hill Education 107 Acidification of the Urine
© 2019 McGraw-Hill Education 108 Acid-Base Regulation (3) 4. Aside from the Na+/H+ pumps in the proximal tubule, the distal tubule has H+ ATPase pumps to increase H+ secretion.
© 2019 McGraw-Hill Education 109 Acid-Base Regulation (4) 5. pH Disturbances a. Kidneys can help compensate for respiratory problems b. Alkalosis: Less H+ is available to transport bicarbonate into tubule cells, so less bicarbonate is reabsorbed; extra bicarbonate secretion compensates for alkalosis.
© 2019 McGraw-Hill Education 110 Acid-Base Regulation (5) pH Disturbances, Continued c. Acidosis: Proximal tubule can make extra bicarbonate through the metabolism of the amino acid glutamine. 1) Extra bicarbonate enters the blood to compensate for acidosis. 2) Ammonia stays in urine to buffer H+.
© 2019 McGraw-Hill Education 111 Disturbances of Acid-Base Balance TABLE 17.7 Categories of Disturbances in Acid- Base Balance Bicarbonate (mEq/L)* PCO2 (mmHg) Less than 21 21 to 26 More than 26 More than 45 Combined metabolic and respiratory acidosis Respiratory acidosis Metabolic alkalosis and respiratory acidosis 35 to 45 Metabolic acidosis Normal Metabolic alkalosis Less than 35 Metabolic acidosis and respiratory alkalosis Respiratory alkalosis Combined metabolic and respiratory alkalosis *mEq/L = milliequivalents per liter. This is the millimolar concentration of HCO3− multiplied by its valence (×1).
© 2019 McGraw-Hill Education 112 G. Urinary Buffers 1. Nephrons cannot produce urine with a pH below 4.5. 2. To increase H+ secretion, urine must be buffered. a. Phosphates and ammonia buffer the urine. b. Phosphates enter via filtration. c. Ammonia comes from the deamination of amino acids.
© 2019 McGraw-Hill Education 113 VI. Clinical Applications
© 2019 McGraw-Hill Education 114 A. Use of Diuretics (1) 1. Used clinically to control blood pressure and relieve edema (fluid accumulation) a. Diuretics increase urine volume, decreasing blood volume and interstitial fluid volume. b. Many types act on different portions of the nephron.
© 2019 McGraw-Hill Education 115 Use of Diuretics (2) 2. Types of Diuretics a. Loop diuretics: most powerful; inhibit salt transport out of ascending loop of Henle 1) Example: Lasix (Frusemide) 2) Can inhibit up to 25% of water reabsorption b. Thiazide diuretics: inhibit salt transport in distal tubule 1) Can inhibit up to 8% of water reabsorption c. Carbonic anhydrase inhibitors: much weaker; inhibit water reabsorption when bicarbonate is reabsorbed 1) Also promote excretion of bicarbonate
© 2019 McGraw-Hill Education 116 Use of Diuretics (3) Types of Diuretics, Continued d. Osmotic diuretics: reduce reabsorption of water by adding extra solutes to the filtrate 1) Example: Mannitol 2) Can occur as a side effect of diabetes (glucose in urine) e. Potassium-sparing diuretics: Aldosterone receptor antagonists block reabsorption of Na+ and secretion of K+.
© 2019 McGraw-Hill Education 117 Actions of Classes of Diuretics TABLE 17.8 Actions of Different Classes of Diuretics Category of Diuretic Example Mechanism of Action Major Site of Action Loop diuretics Furosemide Inhibits sodium transport Thick segments of ascending limbs Thiazides Hydrochlorothiazide Inhibits sodium transport Last part of ascending limb and first part of distal tubule Carbonic anhydrase inhibitors Acetazolamide Inhibits reabsorption of bicarbonate Proximal tubule Osmotic diuretics Mannitol Reduces osmotic reabsorption of water by reducing osmotic gradient Last part of distal tubule and cortical collecting duct Potassium- sparing diuretics Spironolactone Inhibits action of aldosterone Last part of distal tubule and cortical collecting duct Triamterene Inhibits Na+ reabsorption and K+ secretion Last part of distal tubule and cortical collecting duct
© 2019 McGraw-Hill Education 118 Sites of Action of Clinical Diuretics
© 2019 McGraw-Hill Education 119 B. Renal Function Tests 1. PAH and inulin clearance a. Can diagnose nephritis or renal insufficiency 2. Urinary albumin excretion rate: detects above-normal albumin excretion a. Called microalbuminuria b. Signifies renal damage due to hypertension or diabetes 3. Proteinuria: overexcretion of proteins; signifies nephrotic syndrome
© 2019 McGraw-Hill Education 120 C. Kidney Diseases (1) 1. Acute Renal Failure a. Ability of kidneys to regulate blood volume, pH, and solute concentrations deteriorates in a matter of hours/days. b. Usually due to decreased blood flow through kidneys due to: 1) Atherosclerosis of renal arteries 2) Inflammation of renal tubules 3) Use of certain drugs (NSAIDs)
© 2019 McGraw-Hill Education 121 Kidney Diseases (2) 2. Glomerulonephritis a. Inflammation of the glomerulus b. Autoimmune disease with antibodies produced in response to streptococcus infection c. Many glomeruli are destroyed, and others are more permeable to proteins. d. Loss of proteins from blood reduces blood osmotic pressure and leads to edema.
© 2019 McGraw-Hill Education 122 3. Renal Insufficiency a. Any reduction in renal activity b. Can be caused by glomerulonephritis, diabetes, atherosclerosis, or blockage by kidney stones c. Can lead to high blood pressure, high blood K+ and H+, and uremia = urea in the blood. d. Patients with uremia are placed on a dialysis machine to clear blood of these solutes.
© 2019 McGraw-Hill Education 123 Kidney Diseases (4) 4. Dialysis a. “Artificial” kidney b. Hemodialysis – blood cleansed of wastes as it passes through dialysis fluid c. CAPD – continuous ambulatory peritoneal dialysis – dialysis fluid introduced to the abdominal cavity where wastes can pass out of abdominal blood vessels; fluid is then pumped out of the abdominal cavity

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HUMAN PHYSIOLOGY PDF.pdf

  • 1.
  • 2.
    © 2019 McGraw-HillEducation 2 I. Structure and Function of the Kidneys
  • 3.
    © 2019 McGraw-HillEducation 3 A. Kidney Functions 1. Regulation of the extracellular fluid environment in the body, including: a. Volume of blood plasma (affects blood pressure) b. Wastes c. Electrolytes d. pH e. Secrete erythropoietin
  • 4.
    © 2019 McGraw-HillEducation 4 B. Gross Structure of the Urinary System (1) 1. Introduction a. Urine made in the kidney nephrons drains into the renal pelvis, then down the ureter to the urinary bladder. b. It passes from the bladder through the urethra to exit the body. c. Urine is transported using peristalsis.
  • 5.
    © 2019 McGraw-HillEducation 5 Organs of the Urinary System
  • 6.
    © 2019 McGraw-HillEducation 6 Gross Structure of the Urinary System (2) 2. Kidney Structure a. The kidney has two distinct regions: 1) Renal cortex 2) Renal medulla, made up of renal pyramids and columns b. Each pyramid drains into a minor calyx → major calyx → renal pelvis.
  • 7.
    © 2019 McGraw-HillEducation 7 Kidney Structure (1)
  • 8.
    © 2019 McGraw-HillEducation 8 Radiograph of the Urinary System © SPL/Science Source
  • 9.
    © 2019 McGraw-HillEducation 9 Kidney Stones (1) 1. Nephrolithiasis or kidney stones, are hard objects formed in the kidneys containing crystallized minerals or waste products. 2. About 80% are calcium stones but others can be of magnesium ammonium phosphate or uric acid. 3. The tendency to form stones is increased if a person is dehydrated. 4. Large stones in the calyces or pelvis may obstruct urine flow, and smaller stones (usually less than 5 mm) that pass into a ureter can produce intense pain.
  • 10.
    © 2019 McGraw-HillEducation 10 Kidney Stones (2) 5. Treatment options are: a. Medications are available to help pass kidney stones b. Lithotripsy (shock waves are used to shatter it) c. Surgery
  • 11.
    © 2019 McGraw-HillEducation 11 C. Control of Micturition (1) 1. Detrusor muscles line the wall of the urinary bladder. a. Gap junctions connect smooth muscle cells. b. Innervated by parasympathetic neurons, which release acetylcholine onto muscarinic ACh receptors 2. Sphincters surround urethra. a. Internal urethral sphincter: smooth muscle b. External urethral sphincter: skeletal muscle
  • 12.
    © 2019 McGraw-HillEducation 12 Control of Micturition (2) 3. Stretch receptors in the bladder send information to S2−S4 regions of the spinal cord. a. These neurons normally inhibit parasympathetic nerves to the detrusor muscles, while somatic motor neurons to the external urethral sphincter are stimulated. b. Called the guarding reflex c. Prevents involuntary emptying of bladder
  • 13.
    © 2019 McGraw-HillEducation 13 Control of Micturition (3) 4. Stretch of the bladder initiates the voiding reflex. a. Information about stretch passes up the spinal cord to the micturition center of the pons. b. Parasympathetic neurons cause detrusor muscles to contract rhythmically c. Inhibition of sympathetic innervation of the internal urethral sphincter causes it to relax. d. Person feels the need to urinate and can control when with external urethral sphincter.
  • 14.
    © 2019 McGraw-HillEducation 14 Urinary Incontinence 1. Urinary incontinence is uncontrolled urination due to loss of bladder control and has many possible causes. 2. Stress urinary incontinence is present when urine leakage occurs due to increased abdominal pressure, as during sneezing, coughing, and laughing. 3. This happens in women when the pelvic floor no longer provides adequate support to the urethra due to childbirth or aging. It is often treated by a sling surgery, in which inserted mesh provides additional support for the urethra. 4. In men, urinary incontinence frequently occurs as a result of treatments for prostate cancer.
  • 15.
    © 2019 McGraw-HillEducation 15 Overactive Bladder 1. Overactive bladder involves uncontrolled contractions of the detrusor muscle that produce a great urge to urinate and the leakage of a large volume of urine. 2. This urgency is a hallmark of a person with an overactive bladder, who also usually experiences frequent urinations and other symptoms. 3. Urinary incontinence can be diagnosed by urodynamic testing and includes cystometric tests, in which bladder pressure and compliance (dispensability) are measured as the bladder is filled with warm water and the subject is asked to say when the urge to urinate appears.
  • 16.
    © 2019 McGraw-HillEducation 16 D. Microscopic Kidney Structure (1) 1. Nephron: functional unit of the kidney a. Each kidney has more than a million nephrons. b. Nephron consists of small tubules and associated blood vessels. c. Blood is filtered, fluid enters the tubules, is modified, then leaves the tubules as urine
  • 17.
    © 2019 McGraw-HillEducation 17 Kidney Structure (2)
  • 18.
    © 2019 McGraw-HillEducation 18 Renal Blood Vessels Renal artery → Interlobar arteries → Arcuate arteries → Interlobular arteries → Afferent arterioles Glomerulus → Efferent arterioles → Peritubular capillaries → Interlobular veins → Arcuate veins → Interlobar veins → Renal vein
  • 19.
    © 2019 McGraw-HillEducation 19 Microscopic Kidney Structure (2) 2. Nephron Tubules a. Glomerular (Bowman’s) capsule surrounds the glomerulus. Together, they make up the renal corpuscle. b. Filtrate produced in renal corpuscle passes into the proximal convoluted tubule.
  • 20.
    © 2019 McGraw-HillEducation 20 Microscopic Kidney Structure (3) Nephron Tubules, Continued c. Next, fluid passes into the descending and ascending limbs of the loop of Henle. d. After the loop of Henle, fluid passes into the distal convoluted tubule. e. Finally, fluid passes into the collecting duct. f. The fluid is now urine and will drain into a minor calyx.
  • 21.
    © 2019 McGraw-HillEducation 21 Nephron Tubules & Associated Blood Vessels
  • 22.
    © 2019 McGraw-HillEducation 22 Microscopic Kidney Structure (4) 4. Two Types of Nephrons a. Juxtamedullary: better at making concentrated urine b. Cortical
  • 23.
    © 2019 McGraw-HillEducation 23 Polycystic Kidney Disease (PKD) 1. PKD is a congenital disorder in which the kidneys are enlarged by hundreds to thousands of fluid-filled cysts that form in all segments of the nephron and eventually separate from the tubules. 2. Autosomal dominant polycystic kidney disease accounts for most cases and affects almost 1 in 1,000 people. 3. The gene responsible for 85% of ADPKD is located on chromosome 16 and codes for a protein called polycystin- 1,whereas a gene located on chromosome 4 that codes for polycystin-2 is responsible for the other cases. 4. There is no cure presently available, only treatments for the complications of this disease.
  • 24.
    © 2019 McGraw-HillEducation 24 II. Glomerular Filtration
  • 25.
    © 2019 McGraw-HillEducation 25 A. Glomerular Corpuscle (1) 1. Capillaries of the glomerulus are fenestrated. a. Large pores allow water and solutes to leave but not blood cells and plasma proteins. 2. Fluid entering the glomerular capsule is called filtrate
  • 26.
    © 2019 McGraw-HillEducation 26 Glomerular Corpuscle (2) 3. Filtrates must pass through: a. Capillary fenestrae b. Glomerular basement membrane c. Visceral layer of the glomerular capsule composed of cells called podocytes with extensions called pedicles
  • 27.
    © 2019 McGraw-HillEducation 27 Glomerular Capillaries & Capsule © Professor P.M. Motta and M. Sastellucci/SPL/Science Source
  • 28.
    © 2019 McGraw-HillEducation 28 Glomerular Corpuscle & Filtration Barrier © SPL/Science Source
  • 29.
    © 2019 McGraw-HillEducation 29 Glomerular Corpuscle (3) d. Slits in the pedicles called slit diaphragm pores are the major barrier for the filtration of plasma proteins. 1) Defect here causes proteinuria = proteins in urine. 2) Some albumin is filtered out but is reabsorbed by active endocytosis.
  • 30.
    © 2019 McGraw-HillEducation 30 B. Glomerular Ultrafiltrate (1) 1. Fluid in glomerular capsule gets there via hydrostatic pressure of the blood, colloid osmotic pressure, and very permeable capillaries. 2. These forces produce a net filtration pressure of about 10mmHg
  • 31.
    © 2019 McGraw-HillEducation 31 Formation of Glomerular Ultrafiltrate
  • 32.
    © 2019 McGraw-HillEducation 32 Glomerular Ultrafiltrate (2) 3. Filtration Rates a. Glomerular filtration rate (GFR): volume of filtrate produced by both kidneys each minute = 115 to 125 ml. 1) 180 L/day (~45 gal) 2) Total blood volume is filtered every 40 minutes 3) Most must be reabsorbed immediately
  • 33.
    © 2019 McGraw-HillEducation 33 C. Regulation of Glomerular Filtration Rate (1) 1. Vasoconstriction or dilation of afferent arterioles changes filtration rate. a. Extrinsic regulation via sympathetic nervous system b. Intrinsic regulation via signals from the kidneys; called renal autoregulation
  • 34.
    © 2019 McGraw-HillEducation 34 Regulation of Glomerular Filtration Rate (2) 2. Sympathetic Nerve Effects a. In a fight/flight reaction, there is vasoconstriction of the afferent arterioles. b. Helps divert blood to heart and muscles c. Urine formation decreases to compensate for the drop in blood pressure
  • 35.
    © 2019 McGraw-HillEducation 35 Sympathetic Nerve Effects
  • 36.
    © 2019 McGraw-HillEducation 36 Regulation of Glomerular Filtration Rate (3) 3. Renal Autoregulation a. GFR is maintained at a constant level even when blood pressure (BP) fluctuates greatly. 1) Afferent arterioles dilate if BP < 70. 2) Afferent arterioles constrict if BP > normal. b. Myogenic constriction: Smooth muscles in arterioles sense an increase in blood pressure.
  • 37.
    © 2019 McGraw-HillEducation 37 Regulation of Glomerular Filtration Rate (4) Renal Autoregulation, Continued c. Tubuloglomerular feedback: Cells in the ascending limb of the loop of Henle called macula densa sense a rise in water and sodium as occurs with increased blood pressure (and filtration rate). 1) They send a chemical signal (ATP) to constrict the afferent arterioles.
  • 38.
    © 2019 McGraw-HillEducation 38 Regulation of Glomerular Filtration Rate (5) TABLE 17.1 | Regulation of the Glomerular Filtration Rate (GFR) Regulation Stimulus Afferent Arteriole GFR Sympathetic nerves Activation by baroreceptor reflex or by higher brain centers Constricts Decreases Autoregulation Decreased blood pressure Dilates No change Autoregulation Increased blood pressure Constricts No change
  • 39.
    © 2019 McGraw-HillEducation 39 III. Reabsorption of Salt and Water
  • 40.
    © 2019 McGraw-HillEducation 40 A. Introduction: Reabsorption 1. Reabsorption – return of filtered molecules to the blood 2. 180 L of water is filtered per day, but only 1 to 2 L is excreted as urine. a. This will increase when well hydrated and decrease when dehydrated. b. A minimum 400 ml must be excreted to rid the body of wastes = obligatory water loss. c. 85% of reabsorption occurs in the proximal tubules and descending loop of Henle. This portion is unregulated.
  • 41.
    © 2019 McGraw-HillEducation 41 Filtration and Reabsorption
  • 42.
    © 2019 McGraw-HillEducation 42 B. Reabsorption in the Proximal Tubule (1) 1. The osmolality of filtrate in the glomerular capsule is equal to that of blood plasma (isoosmotic). 2. Na+ is actively transported out of the filtrate into the peritubular blood to set up a concentration gradient to drive osmosis.
  • 43.
    © 2019 McGraw-HillEducation 43 Reabsorption in the Proximal Tubule (2) 3. Active Transport a. Cells of the proximal tubules are joined by tight junctions on the apical side (facing inside the tubule). b. The apical side also contains microvilli. c. These cells have a lower Na+ concentration than the filtrate inside the tubule due to Na+/K+ pumps on the basal side of the cells and low permeability to Na+. d. Na+ from the filtrate diffuses into these cells and is then pumped out the other side.
  • 44.
    © 2019 McGraw-HillEducation 44 Reabsorption in the Proximal Tubule (3) 4. Passive Transport a. The pumping of sodium into the interstitial space attracts negative Cl− out of the filtrate. b. Water then follows Na+ and Cl− into the tubular cells and the interstitial space. c. The ions and water diffuse into the peritubular capillaries.
  • 45.
    © 2019 McGraw-HillEducation 45 Salt and Water Reabsorption in the Proximal Tubule
  • 46.
    © 2019 McGraw-HillEducation 46 Reabsorption in the Proximal Tubule (4) 5. Significance of proximal tubule reabsorption a. 65% of the salt and water is reabsorbed, but that is still too much filtrate b. An additional 20% of water is reabsorbed through the descending limb of the Loop of Henle. 1) Happens continuously and is unregulated 2) The final 15% of water (~27 L) is absorbed later in the nephron under control of the hormone Anti-Diuretic Hormone (ADH). 3) Fluid entering loop of Henle is isotonic to extracellular fluids.
  • 47.
    © 2019 McGraw-HillEducation 47 C. Countercurrent Multiplier System (1) 1. Water cannot be actively pumped out of the tubes, and it will not cross if isotonic to extracellular fluid. a. The structure of the loop of Henle allows for a concentration gradient to be set up for the osmosis of water. b. The ascending portion sets up this gradient.
  • 48.
    © 2019 McGraw-HillEducation 48 Countercurrent Multiplier System (2) 2. Ascending Limb of the Loop of Henle a. Salt (NaCl) is actively pumped into the interstitial fluid from the thick segment of the limb 1) Movement of Na+ down its electrochemical gradient from filtrate into tubule cells powers the secondary active transport of Cl− and K+. 2) Na+ is moved into interstitial space via Na+/K+ pump. Cl− follows Na+ passively due to electrical attraction, and K+ passively diffuses back into filtrate.
  • 49.
    © 2019 McGraw-HillEducation 49 Transport of Ions in the Ascending Limb of the Loop of Henle
  • 50.
    © 2019 McGraw-HillEducation 50 Countercurrent Multiplier System (3) Ascending Limb of the Loop of Henle, Continued b. Walls are not permeable to water, so osmosis cannot occur from the ascending part of the loop. c. Surrounding interstitial fluid becomes increasingly solute concentrated at the bottom of the tube. d. Tubular fluid entering the descending loop of Henle becomes more hypotonic as it descends the loop.
  • 51.
    © 2019 McGraw-HillEducation 51 Countercurrent Multiplier System (4) 3. Descending Limb of the Loop of Henle a. Is not permeable to salt but is permeable to water b. Water is drawn out of the filtrate and into the interstitial space where it is quickly picked up by capillaries. c. As it descends, the fluid becomes more solute concentrated. 1) This is perfect for salt transport out of the fluid in the ascending portion.
  • 52.
    © 2019 McGraw-HillEducation 52 Countercurrent Multiplier System (5)
  • 53.
    © 2019 McGraw-HillEducation 53 Countercurrent Multiplier System (6) 4. Countercurrent Multiplication a. Positive feedback mechanism is created between the two portions of the loop of Henle. 1) The more salt the ascending limb removes, the saltier the fluid entering it will be (due to loss of water in descending limb).
  • 54.
    © 2019 McGraw-HillEducation 54 Countercurrent Multiplier System (7) b. Steps of countercurrent mechanism 1) Interstitial fluid is hypertonic due to NaCl pumped out of the ascending limb 2) Water leaves descending limb by osmosis, making the filtrate hypertonic going into the ascending limb 3) More NaCl in the ascending limb can now be pumped out into the interstitial fluid
  • 55.
    © 2019 McGraw-HillEducation 55 Countercurrent Multiplier System (8) Steps of Countercurrent Mechanism, Continued 4) The greater concentration of the interstitial fluid draws more water from the descending limb 5) Filtrate in ascending limb now more concentrated 6) Continues until the maximum NaCl concentration of the inner medulla is reached.
  • 56.
    © 2019 McGraw-HillEducation 56 Countercurrent Multiplier System (9) c. Vasa Recta 1) Specialized blood vessels around loop of Henle, which also have a descending and ascending portion 2) Help create the countercurrent system because they take in salts in the descending region but lose them again in the ascending region a) Keep salts in the interstitial space
  • 57.
    © 2019 McGraw-HillEducation 57 Countercurrent Multiplier System (10) Vasa Recta, Continued 3) High salt concentration (oncotic pressure) at the beginning of the ascending region pulls in water, which is removed from the interstitial space. a) Also keeps salt concentration in the interstitial space high 4) There are also urea transporters and aquaporins to aid in the countercurrent exchanges
  • 58.
    © 2019 McGraw-HillEducation 58 Countercurrent Exchange in the Vasa Recta
  • 59.
    © 2019 McGraw-HillEducation 59 Countercurrent Multiplier System (11) Vasa Recta, Continued 5. Effects of Urea a. Urea is a waste product of protein metabolism b. Contributes to countercurrent system 1) Transported out of collecting duct and into interstitial fluid 2) Diffuses back into ascending limb and cycles around continuously 3) Helps set up solute concentration gradients
  • 60.
    © 2019 McGraw-HillEducation 60 Role of Urea in Urine Concentration
  • 61.
    © 2019 McGraw-HillEducation 61 Renal Tubule Transport Properties TABLE 17.2 Transport Properties of Different Segments of the Renal Tubules and the Collecting Ducts Passive Transport Nephron Segment Active Transport Salt Water Urea Proximal tubule Na+ Cl− Yes Yes Descending limb of the nephron loop None Maybe Yes No Thin segment of ascending limb None NaCl No Yes Thick segment of ascending limb Na+ Cl− No No Distal tubule Na+ Cl− No** No Collecting duct* Slight Na+ No Yes (ADH) or slight (no ADH) Yes *The permeability of the collecting duct to water depends on the presence of ADH. **The last part of the distal tubule, however, is permeable to water.
  • 62.
    © 2019 McGraw-HillEducation 62 Renal Tubule Osmolality
  • 63.
    © 2019 McGraw-HillEducation 63 D. Collecting Duct and ADH (1) 1. Last stop in urine formation 2. Impermeable to NaCl but permeable to water a. Also influenced by hypertonicity of interstitial space – water will leave via osmosis if able to b. Permeability to water depends on the number of aquaporin channels in the cells of the collecting duct c. Availability of aquaporins determined by ADH (antidiuretic hormone; arginine vasopressin)
  • 64.
    © 2019 McGraw-HillEducation 64 Collecting Duct and ADH (2) 3. ADH binds to receptors on collecting duct cells → cAMP → Protein kinase → Vesicles with aquaporin channels fuse to plasma membrane. a) Water channels are removed without ADH. 4. ADH is produced by neurons in the hypothalamus but stored and released from the posterior pituitary gland a) Release stimulated by an increase in blood osmolality
  • 65.
    © 2019 McGraw-HillEducation 65 ADH Stimulation of Aquaporin Channels
  • 66.
    © 2019 McGraw-HillEducation 66 Homeostasis of Plasma Concentration by ADH
  • 67.
    © 2019 McGraw-HillEducation 67 ADH Secretion and Action TABLE 17.3 Antidiuretic Hormone Secretion and Action Stimulus Receptors Secretion of ADH Effects on Urine Volume Effects on Blood ↑Osmolality (dehydration) Osmoreceptors in hypothalamus Increased Decreased Increased water retention; decreased blood osmolality ↓Osmolality Osmoreceptors in hypothalamus Decreased Increased Water loss increases blood osmolality ↑Blood volume Stretch receptors in left atrium Decreased Increased Decreased blood volume ↓Blood volume Stretch receptors in left atrium Increased Decreased Increased blood volume
  • 68.
    © 2019 McGraw-HillEducation 68 Diabetes Insipidus (1) 1. Diabetes insipidus is characterized by polyuria (a large urine volume), thirst, and polydipsia (drinking a lot of fluids). The urine is dilute, with a hypotonic concentration of less than 300 mOsm. 2. There are two major types of diabetes insipidus: a. Central diabetes insipidus-inadequate secretion of ADH b. Nephrogenic diabetes insipidus- inability of the kidneys to respond to ADH. 3. Nephrogenic diabetes insipidus may be caused by genetic defects in either the aquaporin channels or the ADH receptors.
  • 69.
    © 2019 McGraw-HillEducation 69 Diabetes Insipidus (2) 4. More commonly, it is acquired as a response to drug therapy (from lithium given to treat bipolar disorder) or other causes. 5. People with central diabetes insipidus can take desmopressin when needed, and those with nephrogenic diabetes insipidus must drink a lot of water to prevent dehydration.
  • 70.
    © 2019 McGraw-HillEducation 70 IV. Renal Plasma Clearance
  • 71.
    © 2019 McGraw-HillEducation 71 A. Transport Processes Affecting Renal Clearance (1) 1. Kidneys must also remove excess ions and wastes from the blood. a. Sometimes called renal clearance b. Filtration in the glomerular capsule begins this process. c. Reabsorption returns some substances to the blood (decreases renal clearance) d. Secretion finishes the process when substances are moved from the peritubular capillaries into the tubules. (increases renal clearance)
  • 72.
    © 2019 McGraw-HillEducation 72 Transport Processes Affecting Renal Clearance (2) 2. Excretion Rate a. Excretion rate = (filtration rate + secretion rate) – reabsorption rate b. Used to measure glomerular filtration rate (GFR), an indicator of renal health
  • 73.
    © 2019 McGraw-HillEducation 73 Secretion is the Reverse of Reabsorption
  • 74.
    © 2019 McGraw-HillEducation 74 Transport Processes Affecting Renal Clearance (3) 3. Secretion of Drugs a. Membrane carriers specific to foreign substances transport them into the tubules. b. Called organic anion transporters (OATs) or organic cation transporters (OCTs) c. Carriers are polyspecific – overlap in function d. Very fast; may interfere with action of therapeutic drugs
  • 75.
    © 2019 McGraw-HillEducation 75 B. Clearance of Inulin (1) 1. Inulin is a compound found in garlic, onion, dahlias, and artichokes. a. Great marker of glomerular filtration rate because it is filtered but not reabsorbed or secreted GFR = V × U P V = rate of urine formation U = inulin concentration in urine P = inulin concentration in plasma
  • 76.
    © 2019 McGraw-HillEducation 76 Renal Clearance of Inulin
  • 77.
    © 2019 McGraw-HillEducation 77 Clearance of Inulin (2) 2. Renal Plasma Clearance Calculation a. Volume of plasma from which a substance is completely removed by the kidneys in 1 minute 1) Inulin is filtered only. Clearance = GFR 2) Anything that can be reabsorbed has a clearance < GFR. 3) If a substance is filtered and secreted, it will have a clearance > GFR. 4) Renal plasma clearance uses same formula as GFR.
  • 78.
    © 2019 McGraw-HillEducation 78 Clearance of Inulin (3) Renal Plasma Clearance Calculation, Continued b. Clearance of urea is less than GFR – means some is reabsorbed
  • 79.
    © 2019 McGraw-HillEducation 79 Estimated GFR with Creatinine 1. Creatinine is produced in muscles from creatine and released into the blood plasma, where its concentration is used to help assess kidney function. 2. Creatinine is filtered in the kidneys and not reabsorbed, but it is slightly secreted by the tubules. 3. This gives it a renal plasma clearance a little greater than that of inulin (and thus a little greater than the true GFR). 4. However, its plasma concentration, together with a person’s age, sex, and weight, is frequently used in equations to calculate an estimated GFR (eGFR). 5. The ratio of the plasma concentrations of urea (called a BUN -blood urea nitrogen test) to creatinine provides additional information about kidney health.
  • 80.
    © 2019 McGraw-HillEducation 80 Renal Plasma Clearance TABLE 17.4 Effects of Filtration, Reabsorption, and Secretion on Renal Plasma Clearance Term Definition Effect on Renal Clearance Filtration A substance enters the glomerular ultrafiltrate. Some or all of a filtered substance may enter the urine and be “cleared” from the blood. Reabsorption A substance is transported from the filtrate, through tubular cells, and into the blood. Reabsorption decreases the rate at which a substance is cleared; clearance rate is less than the glomerular filtration rate (GFR). Secretion A substance is transported from peritubular blood, through tubular cells, and into the filtrate. When a substance is secreted by the nephrons, its renal plasma clearance is greater than the GFR. TABLE 17.5 | Renal “Handling” of Different Molecules in the Blood Plasma If Substance Is: Example Concentration in Renal Vein Renal Clearance Rate Not filtered Proteins Same as in renal artery Zero Filtered, not reabsorbed or secreted Inulin Less than in renal artery Equal to GFR (115–125 ml/min) Filtered, partially reabsorbed Urea Less than in renal artery Less than GFR Filtered, completely reabsorbed Glucose Same as in renal artery Zero Filtered and secreted PAH Less than in renal artery; approaches zero Greater than GFR; up to total plasma flow rate (~625 ml/min) Filtered, reabsorbed, and secreted K+ Variable Variable
  • 81.
    © 2019 McGraw-HillEducation 81 C. Clearance of PAH 1. Not all blood delivered to the glomeruli is filtered in each pass, so blood must make several passes to completely clear a substance. 2. PAH (para-aminohippuric acid) is an exogenous molecule injected for measurement of total renal blood flow. 3. Substances not filtered must be secreted into the tubules by active transport from the peritubular capillaries 4. All PAH in the peritubular capillaries will be secreted by OATs, so the time it takes to clear all PAH injected indicates blood flow to these capillaries.
  • 82.
    © 2019 McGraw-HillEducation 82 Renal Clearance of PAH
  • 83.
    © 2019 McGraw-HillEducation 83 D. Reabsorption of Glucose (1) 1. Glucose (and amino acids) is easily filtered out into the glomerular capsule 2. Completely reabsorbed in the proximal tubule via secondary active transport with sodium, facilitated diffusion, and simple diffusion
  • 84.
    © 2019 McGraw-HillEducation 84 Mechanism of Reabsorption in the Proximal Tubule
  • 85.
    © 2019 McGraw-HillEducation 85 Reabsorption of Glucose (2) 3. Glucose/Na+ cotransporters have a transport maximum (Tm). a. If there is too much glucose in the filtrate, it will not be completely reabsorbed because all the carriers are in use (saturated). b. Extra glucose spills over into the urine = glycosuria and is a sign of diabetes mellitus. c. Extra glucose in the blood also results in decreased water reabsorption and possible dehydration.
  • 86.
    © 2019 McGraw-HillEducation 86 V. Renal Control of Electrolyte and Acid-Base Balance
  • 87.
    © 2019 McGraw-HillEducation 87 A. Introduction: Renal Control of Electrolyte and Acid-Base Balance 1. Kidneys match electrolyte (Na+, K+, Cl−, bicarbonate, phosphate) excretion to ingestion. a. Control of Na+ levels is important in blood pressure and blood volume. b. Control of K+ levels is important in healthy skeletal and cardiac muscle activity. c. Aldosterone plays a big role in Na+ and K+ balance.
  • 88.
    © 2019 McGraw-HillEducation 88 B. Role of Aldosterone in Na+/K+ Balance (1) 1. About 90% of filtered Na+ and K+ is reabsorbed early in the nephron. a. This is not regulated. 2. An assessment of what the body needs is made, and aldosterone controls additional reabsorption of Na+ and secretion of K+ in the distal tubule and collecting duct.
  • 89.
    © 2019 McGraw-HillEducation 89 Role of Aldosterone in Na+/K+ Balance (2) 3. Potassium Secretion a. Aldosterone independent response: Increase in blood K+ triggers an increase in the number of K+ channels in the cortical collecting duct. 1) When blood K+ levels drop, these channels are removed. b. Aldosterone-dependent response: Increase in blood K+ triggers adrenal cortex to release aldosterone. 1) This increases K+ secretion in the distal tubule and collecting duct.
  • 90.
    © 2019 McGraw-HillEducation 90 Potassium is Reabsorbed and Secreted
  • 91.
    © 2019 McGraw-HillEducation 91 Role of Aldosterone in Na+/K+ Balance (3) Potassium Secretion, Continued c. Sodium and Potassium 1) Increases in sodium absorption drive extra potassium secretion. 2) Due to: a) Potential difference created by Na+ reabsorption driving K+ through K+ channels b) Stimulation of renin-angiotensin-aldosterone system by water and Na+ in filtrate c) Increased flow rates bend cilia on the cells of the distal tubule, resulting in activation of K+ channels
  • 92.
    © 2019 McGraw-HillEducation 92 Role of Aldosterone in Na+/K+ Balance (4) Potassium Secretion, Continued 4. Control of Aldosterone Secretion a. A rise in blood K+ directly stimulates production of aldosterone in the adrenal cortex. b. A fall in blood Na+ indirectly stimulates production of aldosterone via the renin- angiotensin-aldosterone system.
  • 93.
    © 2019 McGraw-HillEducation 93 C. Juxtaglomerular Apparatus (1) 1. Located where the afferent arteriole comes into contact with the distal tubule
  • 94.
    © 2019 McGraw-HillEducation 94 Juxtaglomerular Apparatus (2) 2. A decrease in plasma Na+ results in a fall in blood volume. a. Sensed by juxtaglomerular apparatus b. Granular cells secrete renin into the afferent arteriole. c. This converts angiotensinogen into angiotensin I. d. Angiotensin-converting enzyme (ACE) converts this into angiotensin II.
  • 95.
    © 2019 McGraw-HillEducation 95 Juxtaglomerular Apparatus (3) 3. Stimulates adrenal cortex to make aldosterone a. Promotes the reabsorption of Na+ from cortical collecting duct b. Promotes secretion of K+ c. Increases blood volume and raises blood pressure
  • 96.
    © 2019 McGraw-HillEducation 96 Juxtaglomerular Apparatus (4) 4. Regulation of Renin Secretion a. Low salt levels result in lower blood volume due to inhibition of ADH secretion. 1) Less water is reabsorbed in collecting ducts and more is excreted in urine. b. Reduced blood volume is detected by granular cells that act as baroreceptors. They then secrete renin. 1) Granular cells are also stimulated by sympathetic innervation from the baroreceptor reflex.
  • 97.
    © 2019 McGraw-HillEducation 97 Homeostasis of Plasma Na+
  • 98.
    © 2019 McGraw-HillEducation 98 Juxtaglomerular Apparatus (5) 5. Macula Densa a. Part of the distal tubule that forms the juxtaglomerular apparatus b. Sensor for tubuloglomerular feedback needed for regulation of glomerular filtration rate 1) When there is more Na+ and H2O in the filtrate, a signal is sent to the afferent arteriole to constrict limiting filtration rate. 2) Controlled via negative feedback
  • 99.
    © 2019 McGraw-HillEducation 99 Juxtaglomerular Apparatus (6) Macula Densa, Continued c. When there is more Na+ and H2O in the filtrate, a signal is sent to the afferent arteriole to inhibit the production of renin. 1) This results in less reabsorption of Na+, allowing more to be excreted. 2) This helps lower Na+ levels in the blood.
  • 100.
    © 2019 McGraw-HillEducation 100 D. Atrial Natriuretic Peptide (1) 1. Increases in blood volume also increase the release of atrial natriuretic peptide hormone from the atria of the heart when atrial walls are stretched. 2. Stimulates kidneys to excrete more salt and therefore more water 3. Decreases blood volume and blood pressure
  • 101.
    © 2019 McGraw-HillEducation 101 Atrial Natriuretic Peptide (2) 1. In addition to atrial natriuretic peptide (ANP), scientists have discovered a natriuretic hormone released by the heart’s ventricles called B-type natriuretic peptide (BNP). 2. BNP is secreted in response to increased volume and pressure within the ventricles, and it acts like ANP to promote diuresis. 3. The secretion of BNP increases in congestive heart failure (CHF) so measurements of the blood level of BNP are used clinically to help diagnose CHF.
  • 102.
    © 2019 McGraw-HillEducation 102 Regulation of Renin and Aldosterone Secretion TABLE 17.6 Regulation of Renin and Aldosterone Secretion Stimulus Effect on Renin Secretion Angiotensin II Production Aldosterone Secretion Mechanisms ↓Blood volume Increased Increased Increased Low blood volume stimulates renal baroreceptors; granular cells release renin. ↑Blood volume Decreased Decreased Decreased Increased blood volume inhibits baroreceptors; increased Na+ in distal tubule acts via macula densa to inhibit release of renin from granular cells. ↑ K+ None Not changed Increased Direct stimulation of adrenal cortex ↑Sympathetic nerve activity Increased Increased Increased α-adrenergic effect stimulates constriction of afferent arterioles; β-adrenergic effect stimulates renin secretion directly.
  • 103.
    © 2019 McGraw-HillEducation 103 E. Relationship Between Na+, K+, and H+ 1. Reabsorption of Na+ stimulates the secretion of other positive ions; K+ and H+ compete. 2. Acidosis stimulates the secretion of H+ and inhibits the secretion of K+ ions; acidosis can lead to hyperkalemia. 3. Alkalosis stimulates the secretion and excretion of more K+. 4. Hyperkalemia stimulates the secretion of K+ and inhibits secretion of H+; can lead to acidosis
  • 104.
    © 2019 McGraw-HillEducation 104 Reabsorption of Na+ and Secretion of K+, and H+
  • 105.
    © 2019 McGraw-HillEducation 105 F. Acid-Base Regulation (1) 1. Kidneys maintain blood pH by reabsorbing bicarbonate and secreting H+; urine is thus acidic. 2. Proximal tubule uses Na+/H+ pumps to exchange Na+ out and H+ in. a. Some of the H+ brought in is used for the reabsorption of bicarbonate. b. Antiport secondary active transport
  • 106.
    © 2019 McGraw-HillEducation 106 Acid-Base Regulation (2) 3. Bicarbonate cannot cross the inner tubule membrane so must be converted to CO2 and H2O using carbonic anhydrase. a. Bicarbonate + H+ → carbonic acid b. Carbonic acid (w/ carbonic anhydrase) → H2O + CO2 c. CO2 can cross into tubule cells, where the reaction reverses and bicarbonate is made again. d. This diffuses into the interstitial space.
  • 107.
    © 2019 McGraw-HillEducation 107 Acidification of the Urine
  • 108.
    © 2019 McGraw-HillEducation 108 Acid-Base Regulation (3) 4. Aside from the Na+/H+ pumps in the proximal tubule, the distal tubule has H+ ATPase pumps to increase H+ secretion.
  • 109.
    © 2019 McGraw-HillEducation 109 Acid-Base Regulation (4) 5. pH Disturbances a. Kidneys can help compensate for respiratory problems b. Alkalosis: Less H+ is available to transport bicarbonate into tubule cells, so less bicarbonate is reabsorbed; extra bicarbonate secretion compensates for alkalosis.
  • 110.
    © 2019 McGraw-HillEducation 110 Acid-Base Regulation (5) pH Disturbances, Continued c. Acidosis: Proximal tubule can make extra bicarbonate through the metabolism of the amino acid glutamine. 1) Extra bicarbonate enters the blood to compensate for acidosis. 2) Ammonia stays in urine to buffer H+.
  • 111.
    © 2019 McGraw-HillEducation 111 Disturbances of Acid-Base Balance TABLE 17.7 Categories of Disturbances in Acid- Base Balance Bicarbonate (mEq/L)* PCO2 (mmHg) Less than 21 21 to 26 More than 26 More than 45 Combined metabolic and respiratory acidosis Respiratory acidosis Metabolic alkalosis and respiratory acidosis 35 to 45 Metabolic acidosis Normal Metabolic alkalosis Less than 35 Metabolic acidosis and respiratory alkalosis Respiratory alkalosis Combined metabolic and respiratory alkalosis *mEq/L = milliequivalents per liter. This is the millimolar concentration of HCO3− multiplied by its valence (×1).
  • 112.
    © 2019 McGraw-HillEducation 112 G. Urinary Buffers 1. Nephrons cannot produce urine with a pH below 4.5. 2. To increase H+ secretion, urine must be buffered. a. Phosphates and ammonia buffer the urine. b. Phosphates enter via filtration. c. Ammonia comes from the deamination of amino acids.
  • 113.
    © 2019 McGraw-HillEducation 113 VI. Clinical Applications
  • 114.
    © 2019 McGraw-HillEducation 114 A. Use of Diuretics (1) 1. Used clinically to control blood pressure and relieve edema (fluid accumulation) a. Diuretics increase urine volume, decreasing blood volume and interstitial fluid volume. b. Many types act on different portions of the nephron.
  • 115.
    © 2019 McGraw-HillEducation 115 Use of Diuretics (2) 2. Types of Diuretics a. Loop diuretics: most powerful; inhibit salt transport out of ascending loop of Henle 1) Example: Lasix (Frusemide) 2) Can inhibit up to 25% of water reabsorption b. Thiazide diuretics: inhibit salt transport in distal tubule 1) Can inhibit up to 8% of water reabsorption c. Carbonic anhydrase inhibitors: much weaker; inhibit water reabsorption when bicarbonate is reabsorbed 1) Also promote excretion of bicarbonate
  • 116.
    © 2019 McGraw-HillEducation 116 Use of Diuretics (3) Types of Diuretics, Continued d. Osmotic diuretics: reduce reabsorption of water by adding extra solutes to the filtrate 1) Example: Mannitol 2) Can occur as a side effect of diabetes (glucose in urine) e. Potassium-sparing diuretics: Aldosterone receptor antagonists block reabsorption of Na+ and secretion of K+.
  • 117.
    © 2019 McGraw-HillEducation 117 Actions of Classes of Diuretics TABLE 17.8 Actions of Different Classes of Diuretics Category of Diuretic Example Mechanism of Action Major Site of Action Loop diuretics Furosemide Inhibits sodium transport Thick segments of ascending limbs Thiazides Hydrochlorothiazide Inhibits sodium transport Last part of ascending limb and first part of distal tubule Carbonic anhydrase inhibitors Acetazolamide Inhibits reabsorption of bicarbonate Proximal tubule Osmotic diuretics Mannitol Reduces osmotic reabsorption of water by reducing osmotic gradient Last part of distal tubule and cortical collecting duct Potassium- sparing diuretics Spironolactone Inhibits action of aldosterone Last part of distal tubule and cortical collecting duct Triamterene Inhibits Na+ reabsorption and K+ secretion Last part of distal tubule and cortical collecting duct
  • 118.
    © 2019 McGraw-HillEducation 118 Sites of Action of Clinical Diuretics
  • 119.
    © 2019 McGraw-HillEducation 119 B. Renal Function Tests 1. PAH and inulin clearance a. Can diagnose nephritis or renal insufficiency 2. Urinary albumin excretion rate: detects above-normal albumin excretion a. Called microalbuminuria b. Signifies renal damage due to hypertension or diabetes 3. Proteinuria: overexcretion of proteins; signifies nephrotic syndrome
  • 120.
    © 2019 McGraw-HillEducation 120 C. Kidney Diseases (1) 1. Acute Renal Failure a. Ability of kidneys to regulate blood volume, pH, and solute concentrations deteriorates in a matter of hours/days. b. Usually due to decreased blood flow through kidneys due to: 1) Atherosclerosis of renal arteries 2) Inflammation of renal tubules 3) Use of certain drugs (NSAIDs)
  • 121.
    © 2019 McGraw-HillEducation 121 Kidney Diseases (2) 2. Glomerulonephritis a. Inflammation of the glomerulus b. Autoimmune disease with antibodies produced in response to streptococcus infection c. Many glomeruli are destroyed, and others are more permeable to proteins. d. Loss of proteins from blood reduces blood osmotic pressure and leads to edema.
  • 122.
    © 2019 McGraw-HillEducation 122 3. Renal Insufficiency a. Any reduction in renal activity b. Can be caused by glomerulonephritis, diabetes, atherosclerosis, or blockage by kidney stones c. Can lead to high blood pressure, high blood K+ and H+, and uremia = urea in the blood. d. Patients with uremia are placed on a dialysis machine to clear blood of these solutes.
  • 123.
    © 2019 McGraw-HillEducation 123 Kidney Diseases (4) 4. Dialysis a. “Artificial” kidney b. Hemodialysis – blood cleansed of wastes as it passes through dialysis fluid c. CAPD – continuous ambulatory peritoneal dialysis – dialysis fluid introduced to the abdominal cavity where wastes can pass out of abdominal blood vessels; fluid is then pumped out of the abdominal cavity