1. Physiology of the Kidneys
Chapter 17
Physiology of the Kidneys
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2. Chapter 17 Outline Overview of Kidney Structure Nephron
Glomerular Filtration
Function of Nephron Segments
Renal Clearance
Hormonal Effects
Na+, K+, H+, & HC03- Relationships
Clinical Aspects
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3. 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
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4. Overview of Kidney Structure
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5. Structure of Urinary System
Fig 17.1
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
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6. 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
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7. Structure of Kidney continued
Fig 17.3
Major calyces join to form renal pelvis which collects urine
Conducts urine to ureters which empty into bladder
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8. 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
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9. Nephron
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10. 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
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11. 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
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12. 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
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13. Fig 17.5
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14. 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
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15. Glomerular (Bowman's) Capsule
PCT
Surrounds glomerulus
Together they form renal corpuscle
Is where glomerular filtration occurs
Filtrate passes into PCT
Fig 17.6
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16. Proximal Convoluted Tubule
Walls consist of single layer of cuboidal cells with millions of microvilli
Which increase surface area for reabsorption
Nephron Function animation
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17. 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
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18. Glomerular Filtration
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19. Glomerular Filtration
Glomerular capillaries & Bowman's capsule form a filter for blood
Glomerular Caps are fenestrated--have large pores between its endothelial cells
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
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20. Glomerular Filtration continued
To enter tubule filtrate must pass through narrow filtration slits formed between pedicels of podycytes of glomerular capsule
Fig 17.8
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21. Fig 17.7
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22. Fig 17.9
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23. Glomerular Ultrafiltrate
Is fluid that enters glomerular capsule, whose filtration was driven by blood pressure
Fig 17.10
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24. 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
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25. 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
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26. Sympathetic Effects Sympathetic activity constricts afferent arteriole
Helps maintain BP & shunts blood to heart & muscles
Fig 17.11
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27. 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
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28. 17-28

29. 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
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30. Function of Nephron Segments
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31. 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)
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32. 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
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33. 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
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34. Insert fig
Fig 17.15
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35. 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
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36. Concentration Gradient in Kidney
In order for H20 to be reabsorbed, interstitial fluid must be hypertonic
Osmolality of medulla interstitial fluid ( 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
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37. Descending Limb LH Is permeable to H20
Is impermeable to, & does not AT, salt
Because deep regions of medulla are m O sm, H20 diffuses out of filtrate until it equilibrates with interstitial fluid
This H20 is reabsorbed by capillaries
Fig 17.17
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38. 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 m O sm) by end of LH
Fig 17.17
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39. 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
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40. 17-44

41. Collecting Duct (CD) Plays important role in water conservation
Is impermeable to salt in medulla
Permeability to H20 depends on levels of ADH
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42. 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
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43. Renal Clearance
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44. 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
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45. 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
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46. 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
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47. 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 don't saturate under normal conditions
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48. Glycosuria Is presence of glucose in urine
Occurs when glucose > mg/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
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49. Hormonal Effects
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50. 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
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51. 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
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52. 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
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53. 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)
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54. 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
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55. 17-69

56. 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
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57. 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 HC03- & excrete H+
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58. 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)
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59. Clinical Aspects
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60. 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 1st part of DCT
Carbonic anhydrase inhibitors prevent H20 reabsorption in PCT when HC0s- is reabsorbed
Osmotic diuretics increase osmotic pressure of filtrate
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61. 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
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62. 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
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63. 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
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
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