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Chapter 17 Chapter 17 Presentation Transcript

  • Chapter 17 Physiology of the Kidneys 17-1
    • Chapter 17 Outline
    • Overview of Kidney Structure
    • Nephron
    • Glomerular Filtration
    • Function of Nephron Segments
    • Renal Clearance
    • Hormonal Effects
    • Na + , K + , H + , & HC0 3 - Relationships
    • Clinical Aspects
    17-2
  • 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 + , HC0 3 -, & others
      • Plasma pH
    17-3
  • Overview of Kidney Structure 17-4
  • Structure of Urinary System
    • Paired kidneys are on either side of vertebral column below diaphragm
      • About size of fist
    • Urine flows from kidneys into ureters which empty into bladder
    Fig 17.1 17-5
  • Structure of Kidney
    • Cortex contains many capillaries & outer parts of nephrons
    • Medulla consists of renal pyramids separated by renal columns
      • Pyramid contains minor calyces which unite to form a major calyx
    Fig 17.2 17-6
  • Structure of Kidney continued
    • Major calyces join to form renal pelvis which collects urine
      • Conducts urine to ureters which empty into bladder
    Fig 17.3 17-7
  • Micturition Reflex (Urination)
    • Actions of internal & external urethral sphincters are regulated by reflex center located in sacral part of cord
    • Filling of bladder activates stretch receptors that send impulses to micturition reflex center
      • This activates Parasymp neurons causing contraction of detrusor muscle that relaxes internal urethral sphincter creating sense of urgency
      • There is voluntary control over external urethral sphincter
    • When urination is consciously initiated, descending motor tracts to micturition center inhibit somatic motor fibers of external urethral sphincter & urine is expelled
    17-8
  • Nephron 17-9
  • Nephron
    • Is functional unit of kidney responsible for forming urine
      • >1 million nephrons/kidney
    • Is a long tube & has associated blood vessels
    Fig 17.2 17-10
  • Renal Blood Vessels
    • Blood enters kidney through renal artery
      • Which divides into interlobar arteries
        • That divide into arcuate arteries that give rise to interlobular arteries
    Fig 17.4 17-11
  • Renal Blood Vessels
    • Interlobular arteries give rise to afferent arterioles which supply glomeruli
    • Glomeruli are mass of capillaries inside glomerular capsule that gives rise to filtrate that enters nephron tubule
    • Efferent arteriole drains glomerulus & delivers that blood to peritubular capillaries ( vasa recta )
    • Blood from peritubular capillaries enters veins
    17-12
  • Fig 17.5 17-13
  • Nephron Tubules
    • Tubular part of nephron begins with glomerular capsule which transitions into proximal convoluted tubule ( PCT ), then to descending & ascending limbs of Loop of Henle ( LH ), & distal convoluted tubule ( DCT )
    • Tubule ends where it empties into collecting duct ( CD )
    Fig 17.2 17-14
  • Glomerular (Bowman's) Capsule
    • Surrounds glomerulus
      • Together they form renal corpuscle
    • Is where glomerular filtration occurs
      • Filtrate passes into PCT
    Fig 17.6 17-15 Glomerular capsule PCT
  • Proximal Convoluted Tubule
    • Walls consist of single layer of cuboidal cells with millions of microvilli
      • Which increase surface area for reabsorption
      • Nephron Function animation
    17-16
  • 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
  • Glomerular Filtration 17-18
  • Glomerular Filtration
    • Glomerular capillaries & Bowman's 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
    • To enter tubule filtrate must pass through narrow filtration slits formed between pedicels of podycytes of glomerular capsule
    Glomerular Filtration continued Fig 17.8 17-20
  • Fig 17.7 17-21
  • Fig 17.9 17-22
  • Glomerular Ultrafiltrate
    • Is fluid that enters glomerular capsule, whose filtration was driven by blood pressure
    Fig 17.10 17-23
  • 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
    17-24
  • Regulation of GFR
    • Is controlled by extrinsic & intrinsic ( autoregulation ) mechanisms
    • Vasoconstriction or dilation of afferent arterioles affects rate of blood flow to glomeruli & thus GFR
    17-25
  • Sympathetic Effects
    • Sympathetic activity constricts afferent arteriole
      • Helps maintain BP & shunts blood to heart & muscles
    Fig 17.11 17-26
  • 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
  • 17-28
  • 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
  • Function of Nephron Segments 17-30
  • Reabsorption of Salt & H 2 0
    • In PCT returns most molecules & H 2 0 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 & H 2 0 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 H 2 0 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
  • Insert fig. 17.14 Fig 17.15 17-34
  • Significance of PCT Reabsorption
    • ≈ 65% Na + , Cl - , & H 2 0 is reabsorbed in PCT & returned to bloodstream
    • An additional 20% is reabsorbed in descending loop of Henle
    • Thus 85% of filtered H 2 0 & 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
  • Concentration Gradient in Kidney
    • In order for H 2 0 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
  • Descending Limb LH
    • Is permeable to H 2 0
    • Is impermeable to, & does not AT, salt
    • Because deep regions of medulla are 1400 m O sm, H 2 0 diffuses out of filtrate until it equilibrates with interstitial fluid
      • This H 2 0 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 H 2 0; permeable to salt; thick part ATs salt out of filtrate
      • AT of salt causes filtrate to become dilute (100 m O sm) by end of LH
    Fig 17.17 17-38
  • Vasa Recta
    • Is important component of countercurrent multiplier
    • Permeable to salt, H 2 0 (via aquaporins ), & urea
    • Recirculates salt, trapping some in medulla interstitial fluid
    • Reabsorbs H 2 0 coming out of descending limb
    • Descending section has urea transporters
    • Ascending section has fenestrated capillaries
    Fig 17.18 17-42
  • 17-44
  • Collecting Duct (CD)
    • Plays important role in water conservation
    • Is impermeable to salt in medulla
    • Permeability to H 2 0 depends on levels of ADH
    17-45
  • ADH
    • Is secreted by post pituitary in response to dehydration
    • Stimulates insertion of aquaporins (water channels) into plasma membrane of CD
    • When ADH is high, H 2 0 is drawn out of CD by high osmolality of interstitial fluid
      • & reabsorbed by vasa recta
    Fig 17.21 17-46
  • Renal Clearance 17-48
  • Renal Clearance
    • Refers to ability of kidney to remove substances from blood & excrete them in urine
    • Occurs by filtration & by secretion
    • Secretion is opposite of reabsorption--substances from vasa recta are transported into tubule & excreted
    • Reabsorption decreases renal clearance; secretion increases clearance
    Fig 17.22 17-49
  • Secretion of Drugs
    • Many drugs, toxins, & metabolites are secreted by organic anion transporters of the PCT
      • Involved in determining half-life of many therapeutic drugs
    17-50
  • Measurement of Renal Blood Flow
    • Not all blood delivered to glomerulus is filtered into glomerular capsule
      • 20% is filtered; rest passes into efferent arteriole & back into circulation
      • Substances that aren't filtered can still be cleared by active transport (secretion) into tubules
    17-55
  • 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 ( T m )
      • Glucose & amino acid transporters don't 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 + , HC0 3 - , Cl-, & PO 4 -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 + B alance
    • 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
  • 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 H 2 O 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
  • Macula Densa
    • Is region of 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
    Fig 17.26 17-68
  • 17-69
  • Atrial Natriuretic Peptide (ANP)
    • Is produced by atria due to stretching of walls
    • Acts opposite to aldosterone
    • Stimulates salt & H 2 0 excretion
    • Acts as an endogenous diuretic
    17-70
  • Renal Acid-Base Regulation
    • Kidneys help regulate blood pH by excreting H + &/or reabsorbing HC0 3 -
    • 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
  • Urinary Buffers
    • Nephron cannot produce urine with pH < 4.5
    • Excretes more H + by buffering H + s with HPO 4 -2 or NH 3 before excretion
    • Phosphate enters tubule during filtration
    • Ammonia produced in tubule by deaminating amino acids
    • Buffering reactions
          • HPO 4 -2 + H +  H 2 PO 4 -
          • NH 3 + H +  NH 4 + (ammonium ion)
    17-76
  • Clinical Aspects 17-77
  • Diuretics
    • Are used to lower blood volume because of hypertension, congestive heart failure, or edema
    • Increase volume of urine by increasing proportion of glomerular filtrate that is excreted
    • Loop diuretics are most powerful; inhibit AT salt in thick ascending limb of LH
    • Thiazide diuretics inhibit NaCl reabsorption in 1 st part of DCT
    • Carbonic anhydrase inhibitors prevent H 2 0 reabsorption in PCT when HC0 s - is reabsorbed
    • Osmotic diuretics increase osmotic pressure of filtrate
    17-78
  • 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
    • In renal insufficiency , nephrons have been destroyed as a result of a disease
      • Clinical manifestations include salt & H 2 0 retention & uremia (high plasma urea levels)
        • Uremia is accompanied by high plasma H + & K + which can cause uremic coma
      • Treatment includes hemodialysis
        • Patient's 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
    Kidney Diseases continued 17-82