Principles of Human Anatomy and Physiology, 11e1 Chapter 26 The Urinary System Lecture Outline.
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Transcript of Principles of Human Anatomy and Physiology, 11e1 Chapter 26 The Urinary System Lecture Outline.
Principles of Human Anatomy and Physiology, 11e 1
Chapter 26
The Urinary System
Lecture Outline
Principles of Human Anatomy and Physiology, 11e 2
INTRODUCTION
• The urinary system consists of two kidneys, two ureters, one urinary bladder, and one urethra (Figure 26.1).
• Urine is excreted from each kidney through its ureter and is stored in the urinary bladder until it is expelled from the body through the urethra.
• The specialized branch of medicine that deals with structure, function, and diseases of the male and female urinary systems and the male reproductive system is known as nephrology. The branch of surgery related to male and female urinary systems and the male reproductive system is called urology.
Principles of Human Anatomy and Physiology, 11e 3
Chapter 26The Urinary System
• Kidneys, ureters, urinary bladder & urethra
• Urine flows from each kidney, down its ureter to the bladder and to the outside via the urethra
• Filter the blood and return most of water and solutes to the bloodstream
Principles of Human Anatomy and Physiology, 11e 4
Overview of Kidney Functions
• Regulation of blood ionic composition– Na+, K+, Ca+2, Cl- and phosphate ions
• Regulation of blood pH, osmolarity & glucose• Regulation of blood volume
– conserving or eliminating water• Regulation of blood pressure
– secreting the enzyme renin– adjusting renal resistance
• Release of erythropoietin & calcitriol• Excretion of wastes & foreign substances
Principles of Human Anatomy and Physiology, 11e 5
ANATOMY AND HISTOLOGY OF THE KIDNEYS
• The paired kidneys are retroperitoneal organs (Figure 26.2).
Principles of Human Anatomy and Physiology, 11e 6
External Anatomy of the Kidney
• Near the center of the concave medial border of the kidney is a vertical fissure called the hilus, through which the ureter leaves and blood vessels, lymphatic vessels, and nerves enter and exit (Figure 26.3).
• Three layers of tissue surround each kidney: the innermost renal capsule, the adipose capsule, and the outer renal fascia.
• Nephroptosis is an inferior displacement of the kidneys. It most often occurs in thin people. This condition is dangerous because the ureters may kink and block urine flow (Clinical Application).
Principles of Human Anatomy and Physiology, 11e 7
External Anatomy of Kidney
• Paired kidney-bean-shaped organ• 4-5 in long, 2-3 in wide,
1 in thick• Found just above the waist
between the peritoneum & posterior wall of abdomen– retroperitoneal (along with
adrenal glands & ureters)• Protected by 11th & 12th ribs with
right kidney lower
Principles of Human Anatomy and Physiology, 11e 8
External Anatomy of Kidney
• Blood vessels & ureter enter hilus of kidney• Renal capsule = transparent membrane maintains organ shape• Adipose capsule that helps protect from trauma • Renal fascia = dense, irregular connective tissue that holds against back
body wall
Principles of Human Anatomy and Physiology, 11e 9
External Anatomy of Kidney
Principles of Human Anatomy and Physiology, 11e 10
Internal Anatomy of the Kidney
• Internally, the kidneys consist of cortex, medulla, pyramids, papillae, columns, calyces, and pelves (Figure 26.3).
• The renal cortex and renal pyramids constitute the functional portion or parenchyma of the kidney.
• The nephron is the functional unit of the kidney.
Principles of Human Anatomy and Physiology, 11e 11
Internal Anatomy of the Kidneys
• Parenchyma of kidney– renal cortex = superficial layer of kidney– renal medulla
• inner portion consisting of 8-18 cone-shaped renal pyramids separated by renal columns
• renal papilla point toward center of kidney• Drainage system fills renal sinus cavity
– cuplike structure (minor calyces) collect urine from the papillary ducts of the papilla
– minor & major calyces empty into the renal pelvis which empties into the ureter
Principles of Human Anatomy and Physiology, 11e 12
Internal Anatomy of Kidney
• What is the difference between renal hilus & renal sinus?
• Outline a major calyx & the border between cortex & medulla.
Principles of Human Anatomy and Physiology, 11e 13
Blood and Nerve Supply of the Kidneys
• Blood enters the kidney through the renal artery and exits via the renal vein. – Figures 26.4 and 26.5 show the branching pattern of
renal blood vessels and the path of blood flow through the kidneys.
• In a kidney transplant a donor kidney is placed in the pelvis of the recipient through an abdominal incision. The renal artery, renal vein, and ureter of the donor kidney are connected to the corresponding structure in the recipient. The patient is then placed on immunosuppressive drugs to prevent rejection of the transplanted kidney.
Principles of Human Anatomy and Physiology, 11e 14
Blood & Nerve Supply of Kidney• Abundantly supplied with blood vessels
– receive 25% of resting cardiac output via renal arteries• Functions of different capillary beds
– glomerular capillaries where filtration of blood occurs• vasoconstriction & vasodilation of afferent & efferent
arterioles produce large changes in renal filtration– peritubular capillaries that carry away reabsorbed
substances from filtrate– vasa recta supplies nutrients to medulla without disrupting
its osmolarity form• The nerve supply to the kidney is derived from the renal
plexus (sympathetic division of ANS). Sympathetic vasomotor nerves regulate blood flow & renal resistance by altering arterioles
Principles of Human Anatomy and Physiology, 11e 15
Principles of Human Anatomy and Physiology, 11e 16
Nephrons
• A nephron consists of a renal corpuscle where fluid is filtered, and a renal tubule into which the filtered fluid passes (Figure 26.5).
• Nephrons perform three basic functions: glomerular filtration, tubular reabsorption, and tubular secretion.
• A renal tubule consists of a proximal convoluted tubule (PCT), loop of Henle (nephron loop), and distal convoluted tubule (DCT).
• Distal convoluted tubules of several nephrons drain into to a single collecting duct and many collecting ducts drain into a small number of papillary ducts.
Principles of Human Anatomy and Physiology, 11e 17
Blood Vessels around the Nephron
• Glomerular capillaries are formed between the afferent & efferent arterioles
• Efferent arterioles give rise to the peritubular capillaries and vasa recta
Principles of Human Anatomy and Physiology, 11e 18
Nephrons
• The loop of Henle consists of a descending limb, a thin ascending limb, and a thick ascending limb (Figure 26.5).
• There are two types of nephrons that have differing structure and function.– A cortical nephron usually has its glomerulus in the outer
portion of the cortex and a short loop of Henle that penetrates only into the outer region of the medulla (Figure 26.5a).
– A juxtamedullary nephron usually has its glomerulus deep in the cortex close to the medulla; its long loop of Henle stretches through the medulla and almost reaches the renal papilla (Figure 26.5b).
Principles of Human Anatomy and Physiology, 11e 19
Blood Supply to the Nephron
Principles of Human Anatomy and Physiology, 11e 20
The Nephron
• Kidney has over 1 million nephrons composed of a corpuscle and tubule
• Renal corpuscle = site of plasma filtration– glomerulus is capillaries where filtration occurs– glomerular (Bowman’s) capsule is double-
walled epithelial cup that collects filtrate• Renal tubule
– proximal convoluted tubule– loop of Henle dips down into medulla– distal convoluted tubule
• Collecting ducts and papillary ducts drain urine to the renal pelvis and ureter.
Principles of Human Anatomy and Physiology, 11e 21
Cortical Nephron
• 80-85% of nephrons are cortical nephrons• Renal corpuscles are in outer cortex and loops of Henle lie
mainly in cortex
Principles of Human Anatomy and Physiology, 11e 22
Juxtamedullary Nephron
• 15-20% of nephrons are juxtamedullary nephrons• Renal corpuscles close to medulla and long loops of Henle extend into
deepest medulla enabling excretion of dilute or concentrated urine
Principles of Human Anatomy and Physiology, 11e 23
Histology of the Nephron and Collecting Duct
• Glomerular Capsule– The glomerular capsule consists of visceral and parietal
layers (Figure 26.6).– The visceral layer consists of modified simple squamous
epithelial cells called podocytes.– The parietal layer consists of simple squamous
epithelium and forms the outer wall of the capsule.• Fluid filtered from the glomerular capillaries enters the
capsular space, the space between the two layers of the glomerular capsule.
Principles of Human Anatomy and Physiology, 11e 24
Histology of the Nephron & Collecting Duct
• Single layer of epithelial cells forms walls of entire tube
• Distinctive features due to function of each region– microvilli– cuboidal versus simple– hormone receptors
Principles of Human Anatomy and Physiology, 11e 25
Renal Tubule and Collecting Duct
• Table 26.1 illustrates the histology of the cells that form the renal tubule and collecting duct.
• The juxtaglomerular apparatus (JGA) consists of the juxtaglomerular cells of an afferent arteriole and the macula densa. The JGA helps regulate blood pressure and the rate of blood filtration by the kidneys (Figure 26.6).
• Most of the cells of the distal convoluted tubule are principal cells that have receptors for ADH and aldosterone. A smaller number are intercalated cells which play a role in the homeostasis of blood pH.
• The number of nephrons is constant from birth. They may increase in size, but not in number (Clinical Application).
Principles of Human Anatomy and Physiology, 11e 26
Structure of Renal Corpuscle
• Bowman’s capsule surrounds capsular space
– podocytes cover capillaries to form visceral layer– simple squamous cells form parietal layer of capsule
• Glomerular capillaries arise from afferent arteriole & form a ball before emptying into efferent arteriole
Principles of Human Anatomy and Physiology, 11e 27
Histology of Renal Tubule & Collecting Duct
• Proximal convoluted tubule– simple cuboidal with brush border of microvilli
that increase surface area• Descending limb of loop of Henle
– simple squamous• Ascending limb of loop of Henle
– simple cuboidal to low columnar– forms juxtaglomerular apparatus where makes
contact with afferent arteriole• macula densa is special part of ascending
limb• Distal convoluted & collecting ducts
– simple cuboidal composed of principal & intercalated cells which have microvilli
Principles of Human Anatomy and Physiology, 11e 28
Juxtaglomerular Apparatus
• Structure where afferent arteriole makes contact with ascending limb of loop of Henle– macula densa is thickened part of ascending limb– juxtaglomerular cells are modified muscle cells in arteriole
Principles of Human Anatomy and Physiology, 11e 29
Number of Nephrons
• Remains constant from birth– any increase in size of kidney is size increase of
individual nephrons• If injured, no replacement occurs• Dysfunction is not evident until function declines by
25% of normal (other nephrons handle the extra work)
• Removal of one kidney causes enlargement of the remaining until it can filter at 80% of normal rate of 2 kidneys
Principles of Human Anatomy and Physiology, 11e 30
OVERVIEW OF RENAL PHYSIOLOGY
• Nephrons and collecting ducts perform three basic processes while producing urine: glomerular filtration, tubular secretion, and tubular reabsorption (Figure 26.7).
Principles of Human Anatomy and Physiology, 11e 31
Overview of Renal Physiology
• Nephrons and collecting ducts perform 3 basic processes– glomerular filtration
• a portion of the blood plasma is filtered into the kidney– tubular reabsorption
• water & useful substances are reabsorbed into the blood
– tubular secretion• wastes are removed from the blood & secreted into
urine• Rate of excretion of any substance is its rate of
filtration, plus its rate of secretion, minus its rate of reabsorption
Principles of Human Anatomy and Physiology, 11e 32
Overview of Renal Physiology
• Glomerular filtration of plasma• Tubular reabsorption• Tubular secretion
Principles of Human Anatomy and Physiology, 11e 33
GLOMERULAR FILTRATION
• The fluid that enters the capsular space is termed glomerular filtrate.
• The fraction of plasma in the afferent arterioles of the kidneys that becomes filtrate is termed the filtration fraction.
Principles of Human Anatomy and Physiology, 11e 34
Glomerular Filtration
• Blood pressure produces glomerular filtrate• Filtration fraction is 20% of plasma• 48 Gallons/day
filtrate reabsorbedto 1-2 qt. urine
• Filtering capacityenhanced by:– thinness of membrane
& large surface area of
glomerular capillaries– glomerular capillary BP is high due to small size of
efferent arteriole
Principles of Human Anatomy and Physiology, 11e 35
The Filtration Membrane
• The filtering unit of a nephron is the endothelial-capsular membrane. – glomerular endothelium– glomerular basement membrane– slit membranes between pedicels of podocytes.
• Filtered substances move from the blood stream through three barriers: a glomerular endothelial cell, the basal lamina, and a filtration slit formed by a podocyte (Figure 26.8).
• The principle of filtration - to force fluids and solutes through a membrane by pressure - is the same in glomerular capillaries as in capillaries elsewhere in the body.
Principles of Human Anatomy and Physiology, 11e 36
Filtration Membrane
• #1 Stops all cells and platelets• #2 Stops large plasma proteins• #3 Stops medium-sized proteins, not small ones
Principles of Human Anatomy and Physiology, 11e 37
Net Filtration Pressure
• NFP = total pressure that promotes filtration• NFP = GBHP - (CHP + BCOP) = 10mm Hg
Principles of Human Anatomy and Physiology, 11e 38
Net Filtration Pressure
• Glomerular filtration depends on three main pressures, one that promotes and two that oppose filtration (Figure 26.9).
• Filtration of blood is promoted by glomerular blood hydrostatic pressure (BGHP) and opposed by capsular hydrostatic pressure (CHP) and blood colloid osmotic pressure (BCOP). – The net filtration pressure (NFP) is about 10 mm Hg.
• In some kidney diseases, damaged glomerular capillaries become so permeable that plasma proteins enter the filtrate, causing an increase in NFP and GFR and a decrease in BCOP. (Clinical Application)
Principles of Human Anatomy and Physiology, 11e 39
Glomerular Filtration Rate
• Amount of filtrate formed in all renal corpuscles of both kidneys / minute– average adult male rate is 125 mL/min
• Homeostasis requires GFR that is constant– too high & useful substances are lost due to the speed of
fluid passage through nephron– too low and sufficient waste products may not be removed
from the body• Changes in net filtration pressure affects GFR
– filtration stops if GBHP drops to 45mm Hg– functions normally with mean arterial pressures 80-180
Principles of Human Anatomy and Physiology, 11e 40
Regulation of GFR
• The mechanisms that regulate GFR adjust blood flow into and out of the glomerulus and alter the glomerular capillary surface area available for filtration.
• The three principal mechanisms that control GFR are renal autoregulation, neural regulation, and hormonal regulation.
Principles of Human Anatomy and Physiology, 11e 41
Regulation of GFR
Principles of Human Anatomy and Physiology, 11e 42
Renal Autoregulation of GFR
• Mechanisms that maintain a constant GFR despite changes in arterial BP– myogenic mechanism
• systemic increases in BP, stretch the afferent arteriole• smooth muscle contraction reduces the diameter of
the arteriole returning the GFR to its previous level in seconds
– tubuloglomerular feedback• elevated systemic BP raises the GFR so that fluid
flows too rapidly through the renal tubule & Na+, Cl- and water are not reabsorbed
• macula densa detects that difference & releases a vasoconstrictor from the juxtaglomerular apparatus
• afferent arterioles constrict & reduce GFR
Principles of Human Anatomy and Physiology, 11e 43
Neural Regulation of GFR
• Blood vessels of the kidney are supplied by sympathetic fibers that cause vasoconstriction of afferent arterioles
• At rest, renal BV are maximally dilated because sympathetic activity is minimal– renal autoregulation prevails
• With moderate sympathetic stimulation, both afferent & efferent arterioles constrict equally– decreasing GFR equally
• With extreme sympathetic stimulation (exercise or hemorrhage), vasoconstriction of afferent arterioles reduces GFR– lowers urine output & permits blood flow to other tissues
Principles of Human Anatomy and Physiology, 11e 44
Hormonal Regulation of GFR
• Atrial natriuretic peptide (ANP) increases GFR– stretching of the atria that occurs with an increase
in blood volume causes hormonal release• relaxes glomerular mesangial cells increasing
capillary surface area and increasing GFR• Angiotensin II reduces GFR
– potent vasoconstrictor that narrows both afferent & efferent arterioles reducing GFR
Principles of Human Anatomy and Physiology, 11e 45
TUBULAR REABSORPTION AND TUBULAR SECRETION
Principles of Human Anatomy and Physiology, 11e 46
Tubular Reabsorption & Secretion
• Normal GFR is so high that volume of filtrate in capsular space in half an hour is greater than the total plasma volume
• Nephron must reabsorb 99% of the filtrate– PCT with their microvilli do most of work with rest of nephron
doing just the fine-tuning • solutes reabsorbed by active & passive processes• water follows by osmosis• small proteins by pinocytosis
• Important function of nephron is tubular secretion– transfer of materials from blood into tubular fluid
• helps control blood pH because of secretion of H+• helps eliminate certain substances (NH4+, creatinine, K+)
• Table 26.3 compares the amounts of substances that are filtered, reabsorbed, and excreted in urine with the amounts present in blood plasma.
Principles of Human Anatomy and Physiology, 11e 47
Reabsorption Routes
• A substance being reabsorbed can move between adjacent tubule cells or through an individual tubule cell before entering a peritubular capillary (Figure 26.11).
• Fluid leakage between cells is known as paracellular reabsorption.
• In transcellular reabsorption, a substance passes from the fluid in the tubule lumen through the apical membrane of a tubule cell, across the cytosol, and out into interstitial fluid through the basolateral membrane.
Principles of Human Anatomy and Physiology, 11e 48
Reabsorption Routes
• Paracellular reabsorption – 50% of reabsorbed material
moves between cells bydiffusion in some parts oftubule
• Transcellular reabsorption– material moves through
both the apical and basalmembranes of the tubulecell by active transport
Principles of Human Anatomy and Physiology, 11e 49
Transport Mechanisms
• Solute reabsorption drives water reabsorption. The mechanisms that accomplish Na+ reabsorption in each portion of the renal tubule and collecting duct recover not only filtered Na+ but also other electrolytes, nutrients, and water.
Principles of Human Anatomy and Physiology, 11e 50
Transport Mechanisms
• Apical and basolateral membranes of tubule cells have different types of transport proteins
• Reabsorption of Na+ is important
– several transport systems exist to reabsorb Na+
– Na+/K+ ATPase pumps sodium from tubule cell cytosol through the basolateral membrane only
• Water is only reabsorbed by osmosis
– obligatory water reabsorption occurs when water is “obliged” to follow the solutes being reabsorbed
– facultative water reabsorption occurs in collecting duct under the control of antidiuretic hormone
Principles of Human Anatomy and Physiology, 11e 51
Active and Passive Transport Processes
• Transport across membranes can be either active or passive (See Chapter 3).
• In primary active transport the energy derived from ATP is used to “pump” a substance across a membrane.
• In secondary active transport the energy stored in an ion’s electrochemical gradient drives another substance across the membrane.
Principles of Human Anatomy and Physiology, 11e 52
Transport Maximum (Tm)
• Each type of symporter has an upper limit on how fast it can work, called the transport maximum (Tm).
• The mechanism for water reabsorption by the renal tubule and collecting duct is osmosis.
• About 90% of the filtered water reabsorbed by the kidneys occurs together with the reabsorption of solutes such as Na+, Cl-, and glucose.
• Water reabsorption together with solutes in tubular fluid is called obligatory water reabsorption.
• Reabsorption of the final water, facultative reabsorption, is based on need and occurs in the collecting ducts and is regulated by ADH.
Principles of Human Anatomy and Physiology, 11e 53
Glucosuria
• Renal symporters can not reabsorb glucose fast enough if blood glucose level is above 200 mg/mL– some glucose remains in the urine (glucosuria)
• Common cause is diabetes mellitis because insulin activity is deficient and blood sugar is too high
• Rare genetic disorder produces defect in symporter that reduces its effectiveness
Principles of Human Anatomy and Physiology, 11e 54
Reabsorption and Secretion in the Proximal Convoluted Tubule
Principles of Human Anatomy and Physiology, 11e 55
Reabsorption in the Proximal Convoluted Tubule
• The majority of solute and water reabsorption from filtered fluid occurs in the proximal convoluted tubules and most absorptive processes involve Na+.
• Proximal convoluted tubule Na+ transporters promote reabsorption of 100% of most organic solutes, such as glucose and amino acids; 80-90% of bicarbonate ions; 65% of water, Na+, and K+; 50% of Cl-; and a variable amount of Ca+2, Mg+2, and HPO4
-2.
• Normally, 100% of filtered glucose, amino acids, lactic acid, water-soluble vitamins, and other nutrients are reabsorbed in the first half of the PCT by Na+ symporters. Figure 26.12 shows the operation of the main Na+-glucose symporters in PCT cells.
Principles of Human Anatomy and Physiology, 11e 56
Reabsorption in the Proximal Convoluted Tubule
• Na+/H+ antiporters achieve Na+ reabsorption and return filtered HCO3
- and water to the peritubular capillaries (Figure 26.13). PCT cells continually produce the H+ needed to keep the antiporters running by combining CO2 with water to produce H2CO3 which dissociates into H+ and HCO3
-.
• Diffusion of Cl- into interstitial fluid via the paracellular route leaves tubular fluid more positive than interstitial fluid. This electrical potential difference promotes passive paracellular reabsorption of Na+, K+, Ca+2, and Mg+2 (Figure 26.14).
• Reabsorption of Na+ and other solutes creates an osmotic gradient that promotes reabsorption of water by osmosis (Figure 26.15).
Principles of Human Anatomy and Physiology, 11e 57
Reabsorption in the PCT
• Na+ symporters help reabsorb materials from the tubular filtrate
• Glucose, amino acids, lactic acid, water-soluble vitamins and other nutrients are completely reabsorbed in the first half of the proximal convoluted tubule
• Intracellular sodium levels are kept low due to Na+/K+ pump
Reabsorption of Nutrients
Principles of Human Anatomy and Physiology, 11e 58
Reabsorption of Bicarbonate, Na+ & H+ Ions
• Na+ antiporters reabsorb Na+ and secrete H+– PCT cells produce the H+ &
release bicarbonate ion to the peritubular capillaries
– important buffering system• For every H+ secreted into the tubular
fluid, one filtered bicarbonate eventually returns to the blood
Principles of Human Anatomy and Physiology, 11e 59
Secretion of NH3 and NH4+ in the Proximal Convoluted
Tubule
• Urea and ammonia in the blood are both filtered at the glomerulus and secreted by the proximal convoluted tubule cells into the tubules.
• The deamination of the amino acid glutamine by PCT cells generates both NH3 and new HCO3
- (Figure 26.16).
• At the pH inside tubule cells, most NH3 quickly binds to H+ and becomes NH4
+.
• NH4+ can substitute for H+ aboard Na+/H+ antiporters and be
secreted into tubular fluid.
• Na+/HCO3+ symporters provide a route for reabsorbed Na+
and newly formed HCO3- to enter the bloodstream.
Principles of Human Anatomy and Physiology, 11e 60
Passive Reabsorption in the 2nd Half of PCT
• Electrochemical gradients produced by symporters & antiporters causes passive reabsorption of other solutes
• Cl-, K+, Ca+2, Mg+2 and urea passively diffuse into the peritubular capillaries
• Promotes osmosis in PCT (especially permeable due to aquaporin-1 channels
Principles of Human Anatomy and Physiology, 11e 61
Reabsorption in the Loop of Henle
• The loop of Henle sets the stage for independent regulation of both the volume and osmolarity of body fluids.
• Na+-K+-Cl- symporters reclaim Na+, Cl-, and K+ ions from the tubular lumen fluid (Figure 26.15).
• Because K+ leakage channels return much of the K+ back into tubular fluid, the main effect of the Na+-K+-Cl-
symporters is reabsorption of Na+ and Cl-.• Although about 15% of the filtered water is reabsorbed in
the descending limb, little or no water is reabsorbed in the ascending limb.
Principles of Human Anatomy and Physiology, 11e 62
Symporters in the Loop of Henle
• Thick limb of loop of Henle has Na+ K- Cl- symporters that reabsorb these ions
• K+ leaks through K+ channels back into the tubular fluid leaving the interstitial fluid and blood with a negative charge
• Cations passively move to the vasa recta
Principles of Human Anatomy and Physiology, 11e 63
Reabsorption in the DCT
• As fluid flows along the DCT, reabsorption of Na+ and Cl- continues due to Na+-Cl- symporters.– Na+ and Cl- then reabsorbed into peritubular capillaries
• The DCT serves as the major site where parathyroid hormone stimulates reabsorption of Ca+2.
• DCT is not very permeable to water so the solutes are reabsorbed with little accompanying water.
Principles of Human Anatomy and Physiology, 11e 64
Reabsorption and Secretion in the Collecting Duct
• By end of DCT, 95% of solutes & water have been reabsorbed and returned to the bloodstream
• Cells in the collecting duct make the final adjustments– principal cells reabsorb Na+
• Na+ passes through the apical membrane of principal cells via Na+ leakage channels. Sodium pumps actively transport Na+ across the basolateral membrane (Figure 26.16).
– Principal cells secrete a variable amount of K+ (Figure 26.16). • The secretion of K+ through K+ leakage channels in the principal
cells is the main source of K+ that is excreted in urine.• intercalated cells reabsorb K+ & bicarbonate ions and secrete H+
Principles of Human Anatomy and Physiology, 11e 65
Actions of the Principal Cells
• Na+ enters principal cellsthrough leakage channels
• Na+ pumps keep theconcentration of Na+ inthe cytosol low
• Cells secrete variableamounts of K+, to adjustfor dietary changes in K+intake– down concentration gradient due to
Na+/K+ pump • Aldosterone increases Na+ and water
reabsorption & K+ secretion by principal cells by stimulating the synthesis of new pumps and channels.
Principles of Human Anatomy and Physiology, 11e 66
Secretion of H+ and Absorption of Bicarbonate by Intercalated Cells
• Proton pumps (H+ATPases) secrete H+ into tubular fluid– can secrete against a concentration
gradient so urine can be 1000 times more acidic than blood
• Cl-/HCO3- antiporters move bicarbonate ions into the blood– intercalated cells help regulate pH of
body fluids
• Urine is buffered by HPO4 2- and ammonia, both of which combine irreversibly with H+ and are excreted
Principles of Human Anatomy and Physiology, 11e 67
Hormonal Regulation• Hormones that affect Na+, Cl- & water reabsorption and K+
secretion in the tubules– angiotensin II and aldosterone
• decreases GFR by vasoconstricting afferent arteriole• enhances absorption of Na+• promotes aldosterone production which causes principal cells
to reabsorb more Na+ and Cl- and less water• increases blood volume by increasing water reabsorption
– atrial natriuretic peptide• inhibits reabsorption of Na+ and water in PCT & suppresses
secretion of aldosterone & ADH• increase excretion of Na+ which increases urine output and
decreases blood volume
• Table 26.4 summarizes the hormonal regulation of tubular reabsorption and tubular secretion.
Principles of Human Anatomy and Physiology, 11e 68
Antidiuretic Hormone
• Increases water permeability of principal cells so regulates facultative water reabsorption
• Stimulates the insertion of aquaporin-2 channels into the membrane– water molecules move more rapidly
• When osmolarity of plasma & interstitial fluid decreases, more ADH is secreted and facultative water reabsorption increases.
Principles of Human Anatomy and Physiology, 11e 69
PRODUCTION OF DILUTE AND CONCENTRATED URINE
• The rate at which water is lost from the body depends mainly on ADH, which controls water permeability of principal cells in the collecting duct (and in the last portion of the distal convoluted tubule).
• When ADH level is very low, the kidneys produce dilute urine and excrete excess water; in other words, renal tubules absorb more solutes than water (Figure 26.18).
Principles of Human Anatomy and Physiology, 11e 70
Formation of Concentrated Urine
• Compensation for low water intake or heavy perspiration• When ADH level is high, the kidneys secrete concentrated
urine and conserve water; a large volume of water is reabsorbed from the tubular fluid into interstitial fluid, and the solute concentration of urine is high.
• Production of concentrated urine involves ascending limb cells of the loop of Henle establishing the osmotic gradient in the renal medulla, collecting ducts reabsorbing more water and urea, and urea recycling causing a build up of urea in the renal medulla (Figure 26.19).
• The countercurrent mechanism also contributes to the excretion of concentrated urine.
Principles of Human Anatomy and Physiology, 11e 71
Formation of Concentrated Urine
• Urine can be up to 4 times greater osmolarity than plasma• It is possible for principal cells & ADH to remove water from urine to
that extent, if interstitial fluid surrounding the loop of Henle has high osmolarity– Long loop juxtamedullary nephrons make that possible– Na+/K+/Cl- symporters reabsorb Na+ and Cl- from tubular fluid to
create osmotic gradient in the renal medulla• Cells in the collecting ducts reabsorb more water & urea when ADH is
increased• Urea recycling causes a buildup of urea in the renal medulla• Figure 26.20 summarizes the processes of filtration, reabsorption, and
secretion in each segment of the nephron and collecting ducts. Hormonal effects are also noted.
Principles of Human Anatomy and Physiology, 11e 72
Summary
• H2O Reabsorption – PCT---65%– loop---15%– DCT----10-
15%– collecting
duct---
5-10% with ADH
Principles of Human Anatomy and Physiology, 11e 73
Formation of Dilute Urine
• Dilute = having fewer solutes than plasma (300 mOsm/liter).– diabetes insipidus
• Filtrate and blood have equal osmolarity in PCT
• Water reabsorbed in thin limb, but ions reabsorbed in thick limb of loop of Henle create a filtrate more dilute than plasma– can be 4x as dilute as
plasma– as low as 65 mOsm/liter
• Principal cells do not reabsorb water if ADH is low
Principles of Human Anatomy and Physiology, 11e 74
Countercurrent Mechanism
• Descending limb is very permeable to water– higher osmolarity of interstitial fluid outside the
descending limb causes water to mover out of the tubule by osmosis
• at hairpin turn, osmolarity can reach 1200 mOsm/liter• Ascending limb is impermeable to water, but symporters
remove Na+ and Cl- so osmolarity drops to 100 mOsm/liter, but less urine is left
• Vasa recta blood flowing in opposite directions than the loop of Henle -- provides nutrients & O2 without affecting osmolarity of interstitial fluid
Principles of Human Anatomy and Physiology, 11e 75
Reabsorption within Loop of Henle
Principles of Human Anatomy and Physiology, 11e 76
Clinical Application
• Diuretics are drugs that increase urine flow rate. They work by a variety of mechanisms. The most potent ones are the loop diuretics, such as furosemide, which inhibits the symporters in the thick ascending limb of the loop of Henle.
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Diuretics
• Substances that slow renal reabsorption of water & cause diuresis (increased urine flow rate)– caffeine which inhibits Na+ reabsorption– alcohol which inhibits secretion of ADH– prescription medicines can act on the PCT, loop of
Henle or DCT
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EVALUATION OF KIDNEY FUNCTION
• An analysis of the volume and physical, chemical, and microscopic properties of urine, called urinalysis, reveals much about the state of the body.
• Table 26.5 summarizes the principal physical characteristics of urine.
• Table 26.6 lists several abnormal constituents of urine that may be detected as part of a urinalysis.
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EVALUATION OF KIDNEY FUNCTION
• Two blood screening tests can provide information about kidney function.– One screening test is the blood urea nitrogen (BUN),
which measures the level of nitrogen in blood that is part of urea.
– Another test is measurement of plasma creatinine.• Renal plasma clearance expresses how effectively the
kidneys remove (clear) a substance from blood plasma.– The clearance of inulin gives the glomerular filtration rate.– The clearance of para-aminohippuric acid gives the rate
of renal plasma flow.
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Clinical Application
• Dialysis is the separation of large solutes from smaller ones through use of a selectively permeable membrane.
• Filtering blood through an artificial kidney machine is called hemodialysis. This procedure filters the blood of wastes and adds nutrients.
• A portable method of dialysis is called continuous ambulatory peritoneal dialysis.
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URINE STORAGE, TRANSPORTATION, AND ELIMINATION
• Urine drains through papillary ducts into minor calyces, which joint to become major calyces that unite to form the renal pelvis (Figure 26.3). From the renal pelvis, urine drains into the ureters and then into the urinary bladder, and finally, out of the body by way of the urethra (Figure 26.1).
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Ureters
• Each of the two ureters connects the renal pelvis of one kidney to the urinary bladder (Figure 26.21).
• The ureters transport urine from the renal pelvis to the urinary bladder, primarily by peristalsis, but hydrostatic pressure and gravity also contribute.
• The ureters are retroperitoneal and consist of a mucosa, muscularis, and fibrous coat.
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Anatomy of Ureters
• 10 to 12 in long• diameter from 1-10 mm• Extends from renal pelvis to bladder• Retroperitoneal• Enters posterior wall of bladder• Physiological valve only
– bladder wall compresses arterial opening as it expands during filling
– flow results from peristalsis, gravity & hydrostatic pressure
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Histology of Ureters
• 3 layers in wall– mucosa is transitional epithelium & lamina propria
• since organ must inflate & deflate• mucus prevents the cells from being contacted by urine
– muscularis• inner longitudinal & outer circular smooth muscle layer
– distal 1/3 has additional longitudinal layer• peristalsis contributes to urine flow
– adventitia layer of loose connective tissue anchors in place• contains lymphatics and blood vessels to supply ureter
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Urinary Bladder
• The urinary bladder is a hollow muscular organ situated in the pelvic cavity posterior to the pubic symphysis.
• Anatomy and Histology of the Urinary Bladder• In the floor of the urinary bladder is a small, smooth
triangular area, the trigone. The ureters enter the urinary bladder near two posterior points in the triangle; the urethra drains the urinary bladder from the anterior point of the triangle (Figure 26.21).
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Location of Urinary Bladder
• Posterior to pubic symphysis• In females is anterior to vagina & inferior to uterus• In males lies anterior to rectum
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Anatomy of Urinary Bladder
• Hollow, distensible muscular organ with capacity of 700 - 800 mL• Trigone is smooth flat area bordered by 2 ureteral openings and one
urethral opening
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Histology of Urinary Bladder
• 3 layers in wall– mucosa is transitional epithelium & lamina propria
• since organ must inflate & deflate• mucus prevents the cells from being contacted by urine
– muscularis (known as detrusor muscle)• 3 layers of smooth muscle
– inner longitudinal, middle circular & outer longitudinal• circular smooth muscle fibers form internal urethral
sphincter• circular skeletal muscle forms external urethral sphincter
– adventitia layer of loose connective tissue anchors in place• superior surface has serosal layer (visceral peritoneum)
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Micturition Reflex
• Micturition or urination (voiding)• Stretch receptors signal spinal cord and brain
– when volume exceeds 200-400 mL• Impulses sent to micturition center in sacral spinal cord
(S2 and S3) & reflex is triggered– parasympathetic fibers cause detrusor muscle to
contract, external & internal sphincter muscles to relax• Filling causes a sensation of fullness that initiates a desire
to urinate before the reflex actually occurs– conscious control of external sphincter– cerebral cortex can initiate micturition or delay its
occurrence for a limited period of time
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Anatomy of the Urethra• Females
– length of 1.5 in., orifice between clitoris & vagina– histology
• transitional changing to nonkeratinized stratified squamous epithelium, lamina propria with elastic fibers & circular smooth muscle
• Males– tube passes through prostate, UG diaphragm & penis– 3 regions of urethra
• prostatic urethra, membranous urethra & spongy urethra
• circular smooth muscle forms internal urethral sphincter & UG diaphragm forms external urethral sphincter
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Anatomy of the Urethra
Principles of Human Anatomy and Physiology, 11e 92
Urinary Incontinence
• Lack of voluntary control over micturition– normal in 2 or 3 year olds because neurons to
sphincter muscle is not developed• Stress incontinence in adults
– caused by increases in abdominal pressure that result in leaking of urine from the bladder
• coughing, sneezing, laughing, exercising, walking
– injury to the nerves, loss of bladder flexibility, or damage to the sphincter
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Waste Management in Other Body Systems
• Buffers bind excess H+• Blood transports wastes• Liver is site for metabolic recycling
– conversion of amino acids into glucose, glucose into fatty acids or toxic into less toxic substances
• The lungs excrete CO2. H2O, and heat.• Sweat glands eliminate excess heat, water, and CO2,
plus small quantities of salts and urea.• The GI tract eliminates solid, undigested foods, waste,
some CO2, H2O, salts and heat.
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DEVELOPMENT OF THE URINARY TRACT
• The kidneys develop from intermediate mesoderm.• They develop in the following sequence: pronephros,
mesonephros, and metanephros (Figure 26.22).
Principles of Human Anatomy and Physiology, 11e 95
Developmental Anatomy
• Mesoderm along the posterior aspect attempts to differentiate 3 times into the kidneys
• Pronephros, mesonephros and metanephros
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Later Developmental Anatomy
• By 5th week, the uteric bud forms the duct system• Metanephric mesoderm forms the nephrons• Urogenital sinus forms the bladder and urethra
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Aging and the Urinary System
• After age 40, the effectiveness of kidney function begins to decrease.
• Anatomical changes– kidneys shrink in size from 260 g to 200 g
• Functional changes– lowered blood flow & filter less blood (50%) – diminished sensation of thirst increases susceptibility
to dehydration• Diseases common with age
– acute and chronic inflammations & canaliculi– infections, nocturia, polyuria, dysuria, retention or
incontinence and hematuria• Cancer of prostate is common in elderly men
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Disorders of Urinary System
• Renal calculi• Urinary tract infections• Glomerular disease• Renal failure• Polycystic kidney disease
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DISORDERS: HOMEOSTATIC IMBALANCES
• Crystals of salts present in urine can precipitate and solidify into renal calculi or kidney stones. They may block the ureter and can sometimes be removed by shock wave lithotripsy.
• The term urinary tract infection (UTI) is used to describe either an infection of a part of the urinary system or the presence of large numbers of microbes in urine. UTIs include urethritis (inflammation of the urethra), cystitis (inflammation of the urinary bladder), pyelonephritis (inflammation of the kidneys), and pyelitis (inflammation of the renal pelvis and its calyces).
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Glomerular Diseases
• Glomerulonephritis (Bright’s disease) is an inflammation of the glomeruli of the kidney. One of the most common causes is an allergic reaction to the toxins given off by steptococcal bacteria that have recently infected another part of the body, especially the throat. The glomeruli may be permanently damaged, leading to acute or chronic renal failure.
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Glomerular Diseases
• Chronic renal failure refers to a progressive and generally irreversible decline in glomerular filtration rate that may result from chronic glomerulonephritis, pyelonephritis, polycystic disease, or traumatic loss of kidney tissue.
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Glomerular Diseases
• Polycystic kidney disease is one of the most common inherited disorders. In infants it results in death at birth or shortly thereafter. In adults, it accounts for 6-12% of kidney transplantations. In this disorder, the kidney tubules become riddled with hundreds or thousands of cysts, and inappropriate apoptosis of cells in noncystic tubules leads to progressive impairment of renal function and eventually to renal failure.
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end
Principles of Human Anatomy and Physiology, 11e 104
Chapter 27
Fluid, Electrolyte and Acid-Base Homeostasis
Lecture Outline
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Chapter 27Fluid, Electrolyte and Acid-Base Homeostasis
• Body fluid– all the water and dissolved solutes in
the body’s fluid compartments• Mechanisms regulate
– total volume– distribution– concentration of solutes and pH
• Regulatory mechanisms insure homeostasis of body fluids since their malfunction may seriously endanger nervous system and organ functioning.
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FLUID COMPARTMENTS AND FLUID BALANCE
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Balance Between Fluid Compartments
• Only 2 places for exchange between compartments:– cell membranes separate intracellular from interstitial fluid.– only in capillaries are walls thin enough for exchange between plasma
and interstitial fluids
Volume of fluid in each is kept constant. Since water follows electrolytes, they must be in balance as well
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Introduction
• In lean adults body fluids comprise about 55-60% (Figure 27.1) of total body weight.– Water is the main component of all body fluids.– About two-thirds of the body’s fluid is located in cells and
is called intracellular fluid (ICF).– The other third is called extracellular fluid (ECF).– About 80% of the ECF is interstitial fluid and 20% is
blood plasma.• Some of the interstitial fluid is localized in specific places, such as
lymph; cerebrospinal fluid; gastrointestinal tract fluids; synovial fluid; fluids of the eyes (aqueous humor and vitreous body) and ears (endolymph and perilymph); pleural, pericardial, and peritoneal fluids between serous membranes; and glomerular filtrate in the kidneys.
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Membranes
• Selectively permeable membranes separate body fluids into distinct compartments. – Plasma membranes of individual cells separate
intracellular fluid from interstitial fluid. – Blood vessel walls divide interstitial fluid from blood
plasma. • Although fluids are in constant motion from one
compartment to another, the volume of fluid in each compartment remains fairly stable – another example of homeostasis.
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Fluid and Solute Balance
• Fluid balance means that the various body compartments contain the required amount of water, proportioned according to their needs.– Fluid balance, then, means water balance, but also
implies electrolyte balance; the two are inseparable.• Osmosis is the primary way in which water moves in and out
of body compartments. The concentrations of solutes in the fluids is therefore a major determinant of fluid balance.
• Most solutes in body fluids are electrolytes, compounds that dissociate into ions.
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Body Water Gain and Loss (Figure 27.2)
• 45-75% body weight– declines with age since fat
contains almost no water• Gain from ingestion and
metabolic water formed during aerobic respiration & dehydration synthesis reactions (2500 mL/day)
• Normally loss = gain– urine, feces, sweat, breathe
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Dehydration Stimulates Thirst
• Regulation of fluid gain is by regulation of thirst.
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Regulation of Water Gain
• Metabolic water volume depends mostly on the level of aerobic cellular respiration, which reflects the demand for ATP in body cells.
• The main way to regulate body water balance is by adjusting the volume of water intake.
• When water loss is greater than water gain, dehydration occurs (Figure 27.3).
• The stimulus for fluid intake (gain) is dehydration resulting in thirst sensations; one mechanism for stimulating the thirst center in the hypothalamus is the renin-angiotensin II pathway, which responds to decreased blood volume (therefore, decreased blood pressure) (Figure 27.3).
• Drinking occurs body water levels return to normal
Principles of Human Anatomy and Physiology, 11e 114
Regulation of Water and Solute Loss
• Although increased amounts of water and solutes are lost through sweating and exhalation during exercise, loss of body water or excess solutes depends mainly on regulating how much is lost in the urine (Figure 27.4).
• Under normal conditions, fluid output (loss) is adjusted by – antidiuretic hormone (ADH)– atrial natriuretic peptide (ANP)– aldosterone
all of which regulate urine production.
• Table 27.1 summarizes the factors that maintain body water balance.
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Regulation of Water and Solute Loss
• Elimination of excess water or solutes occurs through urination
• Consumption of very salty meal demonstrates function of three hormones
• Demonstrates how– “water follows salt”– excrete Na+ and water will
follow and decrease blood volume
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Movement of Water Between Body Fluid Compartments
• A fluid imbalance between the intracellular and interstitial fluids can be caused by a change in their osmolarity.
• Most often a change in osmolarity is due to a change in the concentration of Na+.– When water is consumed faster than the kidneys can
excrete it, water intoxication may result (Figure 27.5).– Repeated use of enemas can increase the risk of fluid
and electrolyte imbalances. (Clinical Application)
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Hormone Effects on Solutes
• Angiotensin II and aldosterone promote reabsorption of Na+ and Cl- and an increase in fluid volume– stretches atrial volume and promotes release of ANP– slows release of renin & formation of angiotensin II
• increases filtration rate & reduces water & Na+ reabsorption
• decreases secretion of aldosterone slowing reabsorption of Na+ and Cl- in collecting ducts
• ANP promotes natriuresis or the increased excretion of Na+ and Cl- which decreases blood volume
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Hormone Regulation of Water Balance
• Antidiuretic hormone (ADH) from the posterior pituitary– stimulates thirst– increases permeability of principal cells of collecting ducts
to assist in water reabsorption– very concentrated urine is formed
• ADH secretion shuts off after the intake of water• ADH secretion is increased
– large decrease in blood volume– severe dehydration and drop in blood pressure– vomiting, diarrhea, heavy sweating or burns
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Movement of Water
• Intracellular and interstitial fluidsnormally have the same osmolarity,so cells neither swell nor shrink
• Swollen cells of water intoxicationbecause Na+ concentration of plasmafalls below normal– drink plain water faster than kidneys
canexcrete it
– replace water lost from diarrhea or vomitingwith plain water
– may cause convulsions, coma & death unless oral rehydration includes small amount salt in water intake
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ELECTROLYTES IN BODY FLUIDS• Electrolytes serve four general functions in the body.
– Because they are more numerous than nonelectrolytes, electrolytes control the osmosis of water between body compartments.
– maintain the acid-base balance required for normal cellular activities.
– carry electrical current, which allows production of action potentials and graded potentials and controls secretion of some hormones and neurotransmitters. Electrical currents are also important during development.
– cofactors needed for optimal activity of enzymes.
• Concentration expressed in mEq/liter or milliequivalents per liter for plasma, interstitial fluid and intracellular fluid
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Concentrations of Electrolytes in Body Fluids
• To compare the charge carried by ions in different solutions, the concentration is typically expressed in milliequivalents/liter (mEg/Liter), which gives the concentration of cations or anions in a solution.
• The chief difference between plasma and interstitial fluid– plasma contains quite a few protein anions– interstitial fluid has hardly any since plasma proteins
generally cannot move out of impermeable blood vessel walls
– plasma also contains slightly more sodium ions but fewer chloride ions than the interstitial fluid. In other respects, the two fluids are similar.
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Concentrations of Electrolytes in Body Fluids
• Intracellular fluid (ICF) differs considerably from extracellular fluid (ECF), however.
• Figure 27.6 compares the concentrations of the main electrolytes and protein anions in plasma, interstitial fluid, and intracellular fluid.
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Comparison Between Fluid Components
• Plasma contains many proteins, but interstitial fluid does not– producing blood colloid osmotic pressure
• Extracellular fluid contains Na+ and Cl-• Intracellular fluid contains K+ and phosphates (HPO4 -2)
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Sodium (Na+) is the most abundant extracellular ion.
• Most abundant extracellular ion– accounts for 1/2 of osmolarity of ECF
• Average daily intake exceeds normal requirements• Hormonal controls
– aldosterone causes increased reabsorption Na+– ADH release ceases if Na+ levels too low--dilute
urine lost until Na+ levels rise– ANP increases Na+ and water excretion if Na+
levels too high
• Excess Na+ in the body can result in edema. Excess loss of Na+ causes excessive loss of water, which results in hypovolemia, an abnormally low blood volume. (Clinical Application)
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Edema, Hypovolemia and Na+ Imbalance
• Sodium retention causes water retention– edema is abnormal accumulation of interstitial fluid
• Causes of sodium retention– renal failure– hyperaldosterone
• Excessive loss of sodium causes excessive loss of water (low blood volume)– due to inadequate secretion of aldosterone– too many diuretics
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• Regulation of Cl- balance in body fluids is indirectly controlled by aldosterone. Aldosterone regulate sodium reabsorption; the negatively charged chloride follows the positively charged sodium passively by electrical attraction.
Chloride (Cl-) is the major extracellular anion.
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• Most prevalent extracellular anion• Moves easily between compartments due to Cl- leakage
channels• Helps balance anions in different compartments• Regulation
– passively follows Na+ so it is regulated indirectly by aldosterone levels
– ADH helps regulate Cl- in body fluids because it controls water loss in urine
• Chloride shift across red blood cells with buffer movement• It plays a role in forming HCl in the stomach.
Chloride (Cl-) is the major extracellular anion.
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Potassium (K+) is the most abundant cation in intracellular fluid.
• It is involved in maintaining fluid volume, impulse conduction, muscle contraction.
• Exchanged for H+ to help regulate pH in intracellular fluid• The plasma level of K+ is under the control of
mineralocorticoids, mainly aldosterone.• Helps establish resting membrane potential & repolarize
nerve & muscle tissue• Control is mainly by aldosterone which stimulates principal
cells to increase K+ secretion into the urine• abnormal plasma K+ levels adversely affect cardiac and
neuromuscular function
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Bicarbonate (HCO3-) is a prominent ion in the plasma.
• It is a significant plasma anion in electrolyte balance.• It is a major component of the plasma acid-base buffer
system.– Concentration increases as blood flows through systemic
capillaries due to CO2 released from metabolically active cells
– Concentration decreases as blood flows through pulmonary capillaries and CO2 is exhaled
• Kidneys are main regulator of plasma levels– intercalated cells form more if levels are too low– excrete excess in the urine
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Calcium (Ca+2), the most abundant ion in the body, is principally an extracellular ion.
• It is a structural component of bones and teeth. • Important role in blood clotting, neurotransmitter release,
muscle tone & nerve and muscle function• Regulated by parathyroid hormone
– stimulates osteoclasts to release calcium from bone– increases production of calcitriol (Ca+2 absorption from
GI tract and reabsorption from glomerular filtrate)
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Magnesium (Mg+2) is primarily an intracellular cation.
• It activates several enzyme systems involved in the metabolism of carbohydrates and proteins and is needed for operation of the sodium pump.
• It is also important in neuromuscular activity, neural transmission within the central nervous system, and myocardial functioning.
• Several factors regulate magnesium ion concentration in plasma. They include hypo- or hypercalcemia, hypo- or hypermagnesemia, an increase or decrease in extracellular fluid volume, an increase or decrease in parathyroid hormone, and acidosis or alkalosis.
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Phosphate
• Present as calcium phosphate in bones and teeth, and in phospholipids, ATP, DNA and RNA
• HPO4 -2 is important intracellular anion and acts as buffer of H+ in body fluids and in urine– mono and dihydrogen phosphate act as buffers in the blood
• Plasma levels are regulated by parathyroid hormone & calcitriol– resorption of bone releases phosphate– in the kidney, PTH increase phosphate excretion– calcitriol increases GI absorption of phosphate
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Review
• Table 27.2 describes the imbalances that result from the deficiency or excess of several electrolytes.
Principles of Human Anatomy and Physiology, 11e 134
Clinical Application
• Individuals at risk for fluid and electrolyte imbalances include those dependent on others for fluid and food needs; those undergoing medical treatment involving intravenous infusions, drainage or suction, and urinary catheters, those receiving diuretics, and post-operative individuals, burned individuals, individuals with chronic disease, and those with altered states of consciousness.
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Acid-Base Balance
• The overall acid-base balance of the body is maintained by controlling the H+ concentration of body fluids, especially extracellular fluid.
• Homeostasis of H+ concentration is vital– proteins 3-D structure sensitive to pH changes– normal plasma pH must be maintained between
7.35 - 7.45– diet high in proteins tends to acidify the blood
• 3 major mechanisms to regulate pH– buffer system
– exhalation of CO2 (respiratory system)
– kidney excretion of H+ (urinary system)
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Actions of Buffer Systems
• Prevent rapid, drastic changes in pH• Change either strong acid or base into weaker one• Work in fractions of a second• Found in fluids of the body• 3 principal buffer systems
– protein buffer system– carbonic acid-bicarbonate buffer system– phosphate buffer system
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Protein Buffer System
• Abundant in intracellular fluids & in plasma
– hemoglobin very good at buffering H+ in RBCs
– albumin is main plasma protein buffer
• Amino acids contains at least one carboxyl group (-COOH) and at least one amino group (-NH2)
– carboxyl group acts like an acid & releases H+
– amino group acts like a base & combines with H+
– some side chains can buffer H+
• Hemoglobin acts as a buffer in blood by picking up CO2 or H+
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Carbonic Acid-Bicarbonate Buffer System
• Acts as extracellular & intracellular buffer system
– bicarbonate ion (HCO3-) can act as a weak base
• holds excess H+
– carbonic acid (H2CO3) can act as weak acid
• dissociates into H+ ions• At a pH of 7.4, bicarbonate ion concentration is about 20
times that of carbonic acid• Can not protect against pH changes due to respiratory
problems
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Phosphate Buffer System
• Most important intracellularly, but also acts to buffer acids in the urine
• Dihydrogen phosphate ion acts as a weak acid that can buffer a strong base
• Monohydrogen phosphate acts a weak base by buffering the H+ released by a strong acid
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Exhalation of Carbon Dioxide
• The pH of body fluids may be adjusted by a change in the rate and depth of respirations, which usually takes from 1 to 3 minutes.
• An increase in the rate and depth of breathing causes more carbon dioxide to be exhaled, thereby increasing pH.
• A decrease in respiration rate and depth means that less carbon dioxide is exhaled, causing the blood pH to fall.
• The pH of body fluids, in turn, affects the rate of breathing (Figure 27.7).
• The kidneys excrete H+ and reabsorb HCO3- to aid in
maintaining pH.
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Exhalation of Carbon Dioxide
• pH modified by changing rate & depth of breathing– faster breathing rate, blood
pH rises– slow breathing rate, blood pH
drops• H+ detected by chemoreceptors
in medulla oblongata, carotid & aortic bodies
• Respiratory centers inhibited or stimulated by changes is pH
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Kidney Excretion of H+
• Metabolic reactions produce 1mEq/liter of nonvolatile acid for every kilogram of body weight
• Excretion of H+ in the urine is only way to eliminate huge excess
• Kidneys synthesize new bicarbonate and save filtered bicarbonate
• Renal failure can cause death rapidly due to its role in pH balance
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Regulation of Acid-Base Balance
• Cells in the PCT and collecting ducts secrete hydrogen ions into the tubular fluid.
• In the PCT Na+/H+ antiporters secrete H+ and reabsorb Na+ (Figure 26.13).
• The apical surfaces of some intercalated cells include proton pumps (H+ ATPases) that secrete H+ into the tubular fluid and HCO3
– antiporters in their basolateral membranes to reabsorb HCO3
– (Figure 27.8).
• Other intercalated cells have proton pumps in their basolateral membranes and Cl–/HCO3
– antiporters in their apical membranes.
• These two types of cells help maintain body fluid pH by excreting excess H+ when pH is too low or by excreting excess HCO3
– when the pH is too high.
• Table 27.3 summarizes the mechanism that maintains pH of body fluids.
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Acid-Base Imbalances
• The normal pH range of systemic arterial blood is between 7.35-7.45.
• Acidosis is a blood pH below 7.35. Its principal effect is depression of the central nervous system through depression of synaptic transmission.
• Alkalosis is a blood pH above 7.45. Its principal effect is overexcitability of the central nervous system through facilitation of synaptic transmission.
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Acid-Base Imbalances
• Compensation is an attempt to correct the problem– respiratory compensation– renal compensation
• Acidosis causes depression of CNS---coma• Alkalosis causes excitability of nervous tissue---
spasms, convulsions & death
Acidosis---blood pH below 7.35Alkalosis---blood pH above 7.45
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Acid-Base Imbalances
• Compensation refers to the physiological response to an acid-base imbalance.
• Respiratory acidosis and respiratory alkalosis are primary disorders of blood PCO2.
• metabolic acidosis and metabolic alkalosis are primary disorders of bicarbonate concentration.
• A summary of acidosis and alkalosis is presented in Table 27.4.
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Diagnosis
• Diagnosis of acid-base imbalances employs a general four-step process.– Note whether the pH is high or low relative to the normal
range.
– Decide which value of PCO2 or HCO3- could cause the
abnormality.– Specify the problem source as respiratory or metabolic.– Look at the noncausative value and determine if it is
compensating for the problem.
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Summary of Causes
• Respiratory acidosis & alkalosis are disorders involving changes in partial pressure of CO2 in blood
• Metabolic acidosis & alkalosis are disorders due to changes in bicarbonate ion concentration in blood
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Respiratory Acidosis
• Cause is elevation of pCO2 of blood
• Due to lack of removal of CO2 from blood
– emphysema, pulmonary edema, injury to the brainstem & respiratory centers
• Treatment
– IV administration of bicarbonate (HCO3-)
– ventilation therapy to increase exhalation of CO2
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Respiratory Alkalosis
• Arterial blood pCO2 is too low
• Hyperventilation caused by high altitude, pulmonary disease, stroke, anxiety, aspirin overdose
• Renal compensation involves decrease in excretion of H+ and increase reabsorption of bicarbonate
• Treatment– breathe into a paper bag
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Metabolic Acidosis
• Blood bicarbonate ion concentration too low– loss of ion through diarrhea or kidney dysfunction– accumulation of acid (ketosis with dieting/diabetes)– kidney failing to remove H+ from protein metabolism
• Respiratory compensation by hyperventilation• Treatment
– IV administration of sodium bicarbonate– correct the cause
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Metabolic Alkalosis
• Blood bicarbonate levels are too high• Cause is nonrespiratory loss of acid
– vomiting, gastric suctioning, use of diuretics, dehydration, excessive intake of alkaline drugs
• Respiratory compensation is hypoventilation• Treatment
– fluid and electrolyte therapy– correct the cause
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Diagnosis of Acid-Base Imbalances
• Evaluate – systemic arterial blood pH– concentration of bicarbonate (too low or too high)
– PCO2 (too low or too high)
• Solutions
– if problem is respiratory, the pCO2 will not be normal
– if problem is metabolic, the bicarbonate level will not be normal
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Homeostasis in Infants
• More body water in ECF so more easily disrupted• Rate of fluid intake/output is 7X higher• Higher metabolic rate produces more metabolic wastes• Kidneys can not concentrate urine nor remove excess H+• Surface area to volume ratio is greater so lose more water through skin• Higher breathing rate increase water loss from lungs• Higher K+ and Cl- concentrations than adults
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Impaired Homeostasis in the Elderly
• Decreased volume of intracellular fluid– inadequate fluid intake
• Decreased total body K+ due to loss of muscle tissue or potassium-depleting diuretics for treatment of hypertension or heart disease
• Decreased respiratory & renal function– slowing of exhalation of CO2
– decreased blood flow & glomerular filtration rate– reduced sensitivity to ADH & impaired ability to produce dilute urine– renal tubule cells produce less ammonia to combine with H+ and
excrete as NH+4
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Questions?
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