• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
201 urinary
 

201 urinary

on

  • 296 views

 

Statistics

Views

Total Views
296
Views on SlideShare
296
Embed Views
0

Actions

Likes
0
Downloads
6
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    201 urinary 201 urinary Presentation Transcript

    • Chapter 17Physiology of the Kidneys 17-1
    • Kidney Function• Is to regulate plasma & interstitial fluid by formation of urine• In process of urine formation, kidneys regulate: – Volume of blood plasma, which contributes to BP – Waste products in blood – Concentration of electrolytes • Including Na+, K+, HC03-, & others – Plasma pH 17-3
    • Fig 17.5 17-13
    • Type of Nephrons• Cortical nephrons originate in outer 2/3 of cortex• Juxtamedullary nephrons originate in inner 1/3 cortex – Have long LHs – Important in producing concentrated urine Fig 17.6 17-17
    • Mechanisms of Urine Formation• Urine formation and adjustment of blood composition involves three major processes – Glomerular filtration – Tubular reabsorption – Secretion Figure 25.8
    • Glomerular Filtration• Glomerular capillaries & Bowmans capsule form a filter for blood – Glomerular Caps are fenestrated--have large pores between its endothelial cells • 100-400 times more permeable than other Caps • Small enough to keep RBCs, platelets, & WBCs from passing • Pores are lined with negative charges to keep blood proteins from filtering 17-19
    • Glomerular Filtration continued• To enter tubule filtrate must pass through narrow filtration slits formed between pedicels of podycytes of glomerular capsule Fig 17.8 17-20
    • Filtration• Movement of fluid, derived from blood flowing through the glomerulus, across filtration membrane• Filtrate: water, small molecules, ions that can pass through membrane• Pressure difference forces filtrate across filtration membrane• Renal fraction: part of total cardiac output that passes through the kidneys. Varies from 12-30%; averages 21%• Renal blood flow rate: 1176 mL/min• Renal plasma flow rate: renal blood flow rate X fraction of blood that is plasma: 650 mL/min• Filtration fraction: part of plasma that is filtered into lumen of Bowman’s capsules; average 19%• Glomerular filtration rate (GFR): amount of filtrate produced each minute. 180 L/day• Average urine production/day: 1-2 L. Most of filtrate must be reabsorbed
    • Glomerular Ultrafiltrate• Is fluid that enters glomerular capsule, whose filtration was driven by blood pressure Fig 17.10 17-23
    • Filtration• Filtration membrane: filtration barrier. It prevents blood cells and proteins from entering lumen of Bowman’s capsule, but is many times more permeable than a typical capillary – Fenestrated endothelium, basement membrane and pores formed by podocytes – Some albumin and small hormonal proteins enter the filtrate, but these are reabsorbed and metabolized by the cells of the proximal tubule. Very little protein normally found in urine• Filtration pressure: pressure gradient responsible for filtration; forces fluid from glomerular capillary across membrane into lumen of Bowman’s capsules• Forces that affect movement of fluid into or out of the lumen of Bowman’s capsule – Glomerular capillary pressure (GCP): blood pressure inside capillary tends to move fluid out of capillary into Bowman’s capsule – Capsule pressure (CP): pressure of filtrate already in the lumen – Blood colloid osmotic pressure (BCOP): osmotic pressure caused by proteins in blood. Favors fluid movement into the capillary from the lumen. BCOP greater at end of glomerular capillary than at beginning because of fluid leaving capillary and entering lumen – Filtration pressure (10 mm Hg) = GCP (50 mm Hg) – CP (10 mm
    • Filtration Pressure
    • Filtration• Colloid osmotic pressure in Bowman’s capsule normally close to zero. During diseases like glomerular nephritis, proteins enter the filtrate and filtrate exerts an osmotic pressure, increasing volume of filtrate• High glomerular capillary pressure results from – Low resistance to blood flow in afferent arterioles – Low resistance to blood flow in glomerular capillaries – High resistance to blood flow in efferent arterioles: small diameter vessels• Pressure lower in peritubular capillaries downstream from efferent arterioles• Filtrate is forced across filtration membrane; fluid moves into peritubular capillaries from interstitial fluid• Changes in afferent and efferent arteriole diameter alter filtration pressure – Dilation of afferent arterioles/constriction efferent arterioles increases glomerular capillary pressure, increasing filtration pressure and thus glomerular filtration
    • Net Filtration Pressure (NFP)• The pressure responsible for filtrate formation• NFP equals the glomerular hydrostatic pressure (HPg) minus the oncotic pressure of glomerular blood (OPg) combined with the capsular hydrostatic pressure (HPc) NFP = HPg – (OPg + HPc)
    • Glomerular Filtration Rate (GFR)• Is volume of filtrate produced by both kidneys/min – Averages 115 ml/min in women; 125 ml/min in men – Totals about 180L/day (45 gallons) • So most filtered water must be reabsorbed or death would ensue from water lost through urination• GFR is directly proportional to the NFP• Changes in GFR normally result from changes in glomerular blood pressure 17-24
    • Regulation of Glomerular Filtration• If the GFR is too high: – Needed substances cannot be reabsorbed quickly enough and are lost in the urine• If the GFR is too low: – Everything is reabsorbed, including wastes that are normally disposed of
    • Regulation of Glomerular Filtration• Three mechanisms control the GFR – Renal autoregulation (intrinsic system) – Neural controls – Hormonal mechanism (the renin- angiotensin system)
    • Intrinsic Controls• Under normal conditions, renal autoregulation maintains a nearly constant glomerular filtration rate• Autoregulation entails two types of control – Myogenic – responds to changes in pressure in the renal blood vessels – Flow-dependent tubuloglomerular feedback – senses changes in the juxtaglomerular apparatus
    • Renal Autoregulation• Is also maintained by negative feedback between afferent arteriole & volume of filtrate (tubuloglomerular feedback) – Increased flow of filtrate sensed by macula densa (part of juxtaglomerular apparatus) in thick ascending LH • Signals afferent arterioles to constrict 17-29
    • Renal Autoregulation• Allows kidney to maintain a constant GFR over wide range of BPs• Achieved via effects of locally produced chemicals on afferent arterioles• When average BP drops to 70 mm Hg afferent arteriole dilates• When average BP increases, afferent arterioles constrict 17-27
    • Extrinsic Controls• When the sympathetic nervous system is at rest: – Renal blood vessels are maximally dilated – Autoregulation mechanisms prevail
    • Extrinsic Controls• Under stress: – Norepinephrine is released by the sympathetic nervous system – Epinephrine is released by the adrenal medulla – Afferent arterioles constrict and filtration is inhibited• The sympathetic nervous system also stimulates the renin-angiotensin mechanism
    • Renin-Angiotensin Mechanism• Is triggered when the JG cells release renin• Renin acts on angiotensinogen to release angiotensin I• Angiotensin I is converted to angiotensin II• Angiotensin II: – Causes mean arterial pressure to rise – Stimulates the adrenal cortex to release aldosterone• As a result, both systemic and glomerular hydrostatic pressure rise
    • Sympathetic Effects• Sympathetic activity constricts afferent arteriole – Helps maintain BP & shunts blood to heart & muscles Fig 17.11 17-26
    • 17-28
    • Tubular Reabsorption: Overview• Tubular reabsorption: occurs as filtrate flows through the lumens of proximal tubule, loop of Henle, distal tubule, and collecting ducts• Results because of – Diffusion – Facilitated diffusion – Active transport – Cotransport – Osmosis• Substances transported to interstitial fluid and reabsorbed into peritubular capillaries: inorganic salts, organic molecules, 99% of filtrate volume. These substances return to general circulation through venous system
    • Routes of Water and Solute Reabsorption Figure 25.11
    • Nonreabsorbed Substances• Substances are not reabsorbed if they: – Lack carriers – Are not lipid soluble – Are too large to pass through membrane pores• Urea, creatinine, and uric acid are the most important nonreabsorbed substances
    • Nonreabsorbed Substances• A transport maximum (Tm): – Reflects the number of carriers in the renal tubules available – Exists for nearly every substance that is actively reabsorbed• When the carriers are saturated, excess of that substance is excreted
    • Reabsorption of Salt & H20• In PCT returns most molecules & H20 from filtrate back to peritubular capillaries – About 180 L/day of ultrafiltrate produced; only 1–2 L of urine excreted/24 hours • Urine volume varies according to needs of body • Minimum of 400 ml/day urine necessary to excrete metabolic wastes (obligatory water loss) 17-31
    • Reabsorption of Salt & H20 continued• Return of filtered molecules is called reabsorption• Water is never transported – Other molecules are transported & water follows by osmosis Fig 17.13 17-32
    • PCT• Filtrate in PCT is isosmotic to blood (300 mOsm/L)• Thus reabsorption of H20 by osmosis cannot occur without active transport (AT) – Is achieved by AT of Na+ out of filtrate • Loss of + charges causes Cl- to passively follow Na+ • Water follows salt by osmosis Fig 17.14 17-33
    • Na+ Entry into Tubule Cells• Passive entry: Na+-K+ ATPase pump• In the PCT: facilitated diffusion using symport and antiport carriers• In the ascending loop of Henle: facilitated diffusion via Na+-K+-2Cl− symport system• In the DCT: Na+-Cl– symporter• In collecting tubules: diffusion through membrane pores
    • Insert fig. 17.14 Fig 17.15 17-34
    • Significance of PCT Reabsorption• ≈65% Na+, Cl-, & H20 is reabsorbed in PCT & returned to bloodstream• An additional 20% is reabsorbed in descending loop of Henle• Thus 85% of filtered H20 & salt are reabsorbed early in tubule – This is constant & independent of hydration levels – Energy cost is 6% of calories consumed at rest – The remaining 15% is reabsorbed variably, depending on level of hydration 17-35
    • Absorptive Capabilities of Renal Tubules and Collecting Ducts• Substances reabsorbed in PCT include: – Sodium, all nutrients, cations, anions, and water – Urea and lipid-soluble solutes – Small proteins• Loop of Henle reabsorbs: – H2O, Na+, Cl−, K+ in the descending limb – Ca2+, Mg2+, and Na+ in the ascending limb
    • Absorptive Capabilities of Renal Tubules and Collecting Ducts• DCT absorbs: – Ca2+, Na+, H+, K+, and water – HCO3− and Cl−• Collecting duct absorbs: – Water and urea
    • Concentration Gradient in Kidney• In order for H20 to be reabsorbed, interstitial fluid must be hypertonic• Osmolality of medulla interstitial fluid (1200- 1400 m O sm) is 4X that of cortex & plasma (300 m O sm) – This concentration gradient results largely from loop of Henle which allows interaction between descending & ascending limbs 17-36
    • Osmotic Gradient in the Renal Medulla Figure 25.13
    • Osmolality of Different Regions of the KidneyFig 17.20 17-47
    • Descending Limb LH• Is permeable to H20• Is impermeable to salt• Because deep regions of medulla are 1400 mOsm, H20 diffuses out of filtrate until it equilibrates with interstitial fluid – This H20 is reabsorbed by capillaries Fig 17.17 17-37
    • Ascending Limb LH• Has a thin segment in depths of medulla & thick part toward cortex• Impermeable to H20; permeable to salt; thick part ATs salt out of filtrate – AT of salt causes filtrate to become dilute (100 mOsm) by end of LH Fig 17.17 17-38
    • AT in Ascending Limb LH • Fig 17.16• NaCl is actively extruded from thick ascending limb Insert fig. 17.15 into interstitial fluid• Na+ diffuses into tubular cell with secondary active transport of K+ and Cl-• Occurs at a ratio of 1 Na+ & 1 K+ to 2 Cl- 17-39
    • AT in Ascending Limb LH continued• Na+ is AT across basolateral membrane by Na+/ K+ pump• Cl- passively follows Na+ down electrical gradient• K+ passively diffuses back into filtrate Fig 17.16 17-40
    • Regulation of Urine Concentration and Volume• Osmolality – The number of solute particles dissolved in 1L of water – Reflects the solution’s ability to cause osmosis• Body fluids are measured in milliosmols (mOsm)• The kidneys keep the solute load of body fluids constant at about 300 mOsm• This is accomplished by the countercurrent mechanism
    • Countercurrent Multiplier System• Countercurrent flow & proximity allow descending & ascending limbs of LH to interact in a way that causes osmolality to build in medulla• Salt pumping in thick ascending part raises osmolality around descending limb, causing more H20 to diffuse out of filtrate – This raises osmolality of filtrate in descending limb which causes more concentrated filtrate to be delivered to ascending limb. – As this concentrated filtrate is subjected to AT of salts, it causes even higher osmolality around descending limb (positive feedback) – Process repeats until equilibrium is reached when osmolality of medulla is 1400 mOsm. 17-41
    • Loop of Henle: Countercurrent Mechanism Figure 25.14
    • Formation of Dilute Urine• Filtrate is diluted in the ascending loop of Henle• Dilute urine is created by allowing this filtrate to continue into the renal pelvis• This will happen as long as antidiuretic hormone (ADH) is not being secreted
    • Formation of Dilute Urine• Collecting ducts remain impermeable to water; no further water reabsorption occurs• Sodium and selected ions can be removed by active and passive mechanisms• Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma)
    • Formation of Concentrated Urine• Antidiuretic hormone (ADH) inhibits diuresis• This equalizes the osmolality of the filtrate and the interstitial fluid• In the presence of ADH, 99% of the water in filtrate is reabsorbed
    • Formation of Concentrated Urine• ADH-dependent water reabsorption is called facultative water reabsorption• ADH is the signal to produce concentrated urine• The kidneys’ ability to respond depends upon the high medullary osmotic gradient
    • Formation of Dilute and Concentrated Urine Figure 25.15a, b
    • Vasa Recta Fig 17.18• Is important component of countercurrent multiplier• Permeable to salt, H20 (via aquaporins), & urea• Recirculates salt, trapping some in medulla interstitial fluid• Reabsorbs H20 coming out of descending limb• Descending section has urea transporters• Ascending section has fenestrated capillaries 17-42
    • Effects of Urea• Urea contributes to high osmolality in medulla – Deep region of collecting duct is permeable to urea & transports it Fig 17.19 17-43
    • 17-44
    • Collecting Duct (CD)• Plays important role in water conservation• Is impermeable to salt in medulla• Permeability to H20 depends on levels of ADH 17-45
    • ADH Fig 17.21• Is secreted by post pituitary in response to dehydration• Stimulates insertion of aquaporins (water channels) into plasma membrane of CD• When ADH is high, H20 is drawn out of CD by high osmolality of interstitial fluid – & reabsorbed by vasa recta 17-46
    • Glucose & Amino Acid Reabsorption• Filtered glucose & amino acids are normally 100% reabsorbed from filtrate – Occurs in PCT by carrier-mediated cotransport with Na+ • Transporter displays saturation if ligand concentration in filtrate is too high – Level needed to saturate carriers & achieve maximum transport rate is transport maximum (Tm) – Glucose & amino acid transporters dont saturate under normal conditions 17-58
    • Glycosuria• Is presence of glucose in urine• Occurs when glucose > 180-200mg/100ml plasma (= renal plasma threshold) – Glucose is normally absent because plasma levels stay below this value – Hyperglycemia has to exceed renal plasma threshold – Diabetes mellitus occurs when hyperglycemia results in glycosuria 17-59
    • Hormonal Effects 17-60
    • Electrolyte Balance• Kidneys regulate levels of Na+, K+, H+, HC03-, Cl-, & PO4-3 by matching excretion to ingestion• Control of plasma Na+ is important in regulation of blood volume & pressure• Control of plasma of K+ important in proper function of cardiac & skeletal muscles 17-61
    • Role of Aldosterone in Na+/K+ Balance• 90% filtered Na+ & K+ reabsorbed before DCT – Remaining is variably reabsorbed in DCT & cortical CD according to bodily needs • Regulated by aldosterone (controls K+ secretion & Na+ reabsorption) • In the absence of aldosterone, 80% of remaining Na+ is reabsorbed in DCT & cortical CD • When aldosterone is high all remaining Na+ is reabsorbed 17-62
    • K+ Secretion• Is only way K+ ends up in urine• Is directed by aldosterone & occurs in DCT & cortical CD – High K+ or Na+ will increase aldosterone & K+ secretion Fig 17.25 17-63
    • Juxtaglomerular Apparatus (JGA)• Is specialized region in each nephron where afferent arteriole comes in contact with thick ascending limb LH Fig 17.26 17-64
    • Renin-Angiotensin-Aldosterone System• Is activated by release of renin from granular cells within afferent arteriole – Renin converts angiotensinogen to angiotensin I • Which is converted to Angio II by angiotensin-converting enzyme (ACE) in lungs • Angio II stimulates release of aldosterone 17-65
    • Regulation of Renin Secretion• Inadequate intake of NaCl always causes decreased blood volume – Because lower osmolality inhibits ADH, causing less H2O reabsorption – Low blood volume & renal blood flow stimulate renin release • Via direct effects of BP on granular cells & by Symp activity initiated by arterial baroreceptor reflex (see Fig 14.26) 17-66
    • Fig 17.27 17-67
    • Macula Densa• Is region of Fig 17.26 ascending limb in contact with afferent arteriole• Cells respond to levels of Na+ in filtrate – Inhibit renin secretion when Na+ levels are high – Causing less aldosterone secretion, more Na+ excretion 17-68
    • Renin Release Figure 25.10
    • 17-69
    • Atrial Natriuretic Peptide (ANP)• Is produced by atria due to stretching of walls• Acts opposite to aldosterone• Stimulates salt & H20 excretion• Acts as an endogenous diuretic 17-70
    • Na , K , H , & HC03 + + + - Relationships 17-71
    • Na+, K+, & H+ Relationship• Na+ reabsorption in DCT & CD creates electrical gradient for H+ & K+ secretion Insert fig. 17.27• When extracellular H+ increases, H+ moves into cells causing K+ to diffuse out & vice versa – Hyperkalemia can cause acidosis Fig 17.28• In severe acidosis, H is + secreted at expense of K+ 17-72
    • Renal Acid-Base Regulation• Kidneys help regulate blood pH by excreting H + &/or reabsorbing HC03-• Most H+ secretion occurs across walls of PCT in exchange for Na+ (Na+/H+ antiporter)• Normal urine is slightly acidic (pH = 5-7) because kidneys reabsorb almost all HC0 3- & excrete H+ 17-73
    • Reabsorption of HCO3- in PCT• Is indirect because apical membranes of PCT cells are impermeable to HCO3- 17-74
    • Reabsorption of HCO3- in PCT continued• When urine is acidic, HCO3- combines with H+ to form H2C03 (catalyzed by CA on apical membrane of PCT cells)• H2C03 dissociates into C02 + H2O• C02 diffuses into PCT cell & forms H2C03 (catalyzed by CA)• H2C03 splits into HCO3- & H+ ; HCO3- diffuses into blood Fig 17.29 17-75
    • Urinary Buffers• Nephron cannot produce urine with pH < 4.5• Excretes more H+ by buffering H+s with HPO4-2 or NH3 before excretion• Phosphate enters tubule during filtration• Ammonia produced in tubule by deaminating amino acids• Buffering reactions – HPO4-2 + H+ → H2PO4- – NH3 + H+ → NH4+ (ammonium ion) 17-76
    • Physical Characteristics of Urine• Color and transparency – Clear, pale to deep yellow (due to urochrome) – Concentrated urine has a deeper yellow color – Drugs, vitamin supplements, and diet can change the color of urine – Cloudy urine may indicate infection of the urinary tract
    • Physical Characteristics of Urine• Odor – Fresh urine is slightly aromatic – Standing urine develops an ammonia odor – Some drugs and vegetables (asparagus) alter the usual odor
    • Physical Characteristics of Urine• pH – Slightly acidic (pH 6) with a range of 4.5 to 8.0 – Diet can alter pH• Specific gravity – Ranges from 1.001 to 1.035 – Is dependent on solute concentration
    • Urethra Figure 25.18a. b
    • Micturition (Voiding or Urination)• The act of emptying the bladder• Distension of bladder walls initiates spinal reflexes that: – Stimulate contraction of the external urethral sphincter – Inhibit the detrusor muscle and internal sphincter (temporarily)• Voiding reflexes: – Stimulate the detrusor muscle to contract – Inhibit the internal and external sphincters
    • Micturition (Voiding or Urination)
    • Kidney Diseases• In acute renal failure, ability of kidneys to excrete wastes & regulate blood volume, pH, & electrolytes is impaired – Rise in blood creatinine & decrease in renal plasma clearance of creatinine – Can result from atherosclerosis, inflammation of tubules, kidney ischemia, or overuse of NSAIDs 17-80
    • Kidney Diseases continued• Glomerulonephritis is inflammation of glomeruli – Autoimmune attack against glomerular capillary basement membranes • Causes leakage of protein into urine resulting in decreased colloid osmotic pressure & resulting edema 17-81
    • Kidney Diseases continued• In renal insufficiency, nephrons have been destroyed as a result of a disease – Clinical manifestations include salt & H20 retention & uremia (high plasma urea levels) • Uremia is accompanied by high plasma H+ & K+ which can cause uremic coma – Treatment includes hemodialysis • Patients blood is passed through a dialysis machine which separates molecules on basis of ability to diffuse through selectively permeable membrane • Urea & other wastes are removed 17-82