1. Chapter 17 Lecture Outline
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2. Chapter 17 Outline Structure and Function of the Kidney
Glomerular Filtration
Reabsorption of Salt and Water
Renal Plasma Clearance
Renal Control of Electrolyte and Acid-Base Balance
Clinical Applications
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3. Kidney Function
Is to regulate plasma and interstitial fluid by formation of urine
In process of urine formation, kidneys regulate:
Volume of blood plasma, which contributes to BP
Waste products in plasma
Concentration of electrolytes
Including Na+, K+, HCO3-, and others
Plasma pH
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4. Gross Structure of the Urinary System
17-4

5. 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
Urethra drains urine from bladder
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6. Structure of Kidney
Cortex contains many capillaries and outer parts of nephrons
Medulla consists of renal pyramids separated by renal columns
Pyramid contains minor calyces which unite to form a major calyx
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7. Structure of Kidney continued
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)
Bladder has a smooth muscle wall called the detrussor muscle
Stretch can cause spontaneous Act. Pots. and contraction
Also innervated and controlled by parasympathetic
Drugs for overactive bladders target muscarinic ACh receptors
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9. Micturition Reflex (Urination) continued
Actions of internal and 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 and urine is expelled
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10. Microscopic Structure of the Kidney
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11. Nephron Is functional unit of kidney; responsible for forming urine
>1 million nephrons/kidney
Consists of small tubes and associated small blood vessels
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12. 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
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13. Renal Blood Vessels continued
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 and delivers that blood to peritubular capillaries (vasa recta)
Blood from peritubular capillaries enters interlobular veins
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14. 17-14

15. Nephron Tubules
Tubular part of nephron begins with glomerular capsule which transitions into proximal convoluted tubule (PCT), then to descending and ascending limbs of Loop of Henle (LH), and distal convoluted tubule (DCT)
Tubule ends where it empties into collecting duct (CD)
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16. Glomerular (Bowman's) Capsule
Surrounds glomerulus
Together they form renal corpuscle
Is where glomerular filtration occurs
Filtrate passes into proximal convoluted tubule
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17. Proximal Convoluted Tubule
Walls consist of single layer of cuboidal cells with millions of microvilli
Which increase surface area for reabsorption
During reabsorption, salt, water, and other molecules needed by the body are transported from the lumen through the tubular cells and into surrounding peritubular capillaries
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18. 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
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19. Glomerular Filtration
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20. Glomerular Filtration
Glomerular capillaries and Bowman's capsule form a filter for blood
Glomerular Caps are fenestrated--have large pores between its endothelial cells
Big enough to allow any plasma molecule to pass
times more permeable than other Caps
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21. Glomerular Filtration continued
To enter tubule filtrate must pass through narrow slit diaphragms formed between pedicels (foot processes) of podocytes of glomerular capsule
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22. Glomerular Filtration continued
Plasma proteins are mostly excluded from the filtrate because of large size and negative charge
The slit diaphragms are lined with negative charges which repel negatively-charged proteins
Some protein (especially albumin) normally enters the filtrate but most is reabsorbed by receptor-mediated endocytosis
Defects in the slit diaphragm results in massive leakage of proteinin the filtrate and thus appears in the urine (=proteinuria)
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23. Scanning electron micrograph of glomerular caps and capsule
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24. An electron micrograph of the filtration barrier between the cap lumen & glomer. capsule
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25. The Formation of Glomerular Ultrafiltrate
Only a fraction of plasma proteins (green) are filtered
Smaller plasma solutes (purple) easily enter the glomerular ultrafiltrate
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26. 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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27. Regulation of GFR
Is controlled by extrinsic and intrinsic (autoregulation) mechanisms
Vasoconstriction or dilation of afferent arterioles affects rate of blood flow to glomeruli and thus GFR
17-27

28. Sympathetic Effects Sympathetic activity constricts afferent arteriole
Helps maintain BP and shunts blood to heart and muscles
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29. Renal Autoregulation
Defined as the ability of kidneys to maintain relatively constant GFR in the face of fluctuating B.P.
2 mechanisms responsible:
Myogenic constriction of afferent arteriole due to smooth muscle responding to an inc. in arterial pressure
Achieved via effects of locally produced chemicals on afferent arterioles part of tubuloglomerular feedback
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30. 17-30

31. Renal Autoregulation continued
Is also maintained by negative feedback between afferent arteriole and 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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32. Reabsorption of Salt and Water
17-32

33. Reabsorption of Salt and H2O
In PCT returns most molecules and H2O 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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34. Reabsorption of Salt and H2O continued
The transport of molecules out of the tubular filtrated back into the blood = reabsorption
Water is never transported
Other molecules are transported and water follows by osmosis
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35. The Mech. of Reabsorption in the proximal tubule
There is coupled transport of glucose and Na+ into the cytoplasm &
Primary active transport of Na+ across basolateral membrane by Na+/K+ pump
Glucose is then transported out of cell by facilitated diffusion and is reabsorbed into the blood
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36. Salt and water reabsorption in the proximal tubules:
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37. Significance of PCT Reabsorption
~65% Na+, Cl-, and H2O is reabsorbed in PCT and returned to bloodstream
An additional 20% is reabsorbed in descending loop of Henle
Thus 85% of filtered H2O and salt are reabsorbed early in tubule
This is constant and 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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38. Concentration Gradient in Kidney
In order for H2O to be reabsorbed, interstitial fluid must be hypertonic
Osmolality of medulla interstitial fluid ( mOsm) is 4X that of cortex and plasma (300 mOsm)
This concentration gradient results largely from loop of Henle which allows interaction between descending and ascending limbs
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39. The Countercurrent Multiplier System
Extrusion of NaCl from ascending limb makes surrounding interstitial fluid more concentrated
Multiplication of concent. due to descend. limb passively permeable to water—causing fluid to inc. in concent. as the surrounding interstitial fluid more concent.
Deepest region of medulla at 1,400mOsm
17-39

40. Ascending Limb Loop of Henle
Has a thin segment in depths of medulla and thick part toward cortex
Impermeable to H2O; permeable to salt; thick part Actively Transports salt out of filtrate
Active Transport of salt causes filtrate to become dilute (100 mOsm) by end of Loop of Henle
17-40

41. The Transport of Ions in the Ascending Limb
In thick segment, Na+ and K+ together with 2 Cl- enter tubule cells
Na+ then actively transported out into interstitial space and Cl- follows passively
K+ diffuses back into filtrate; some also enters interstitial space
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42. AT in Ascending Limb LH continued
Na+ is Actively Transported across basolateral membrane by Na+/ K+ pump
Cl- passively follows Na+ down electrical gradient
K+ passively diffuses back into filtrate
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43. Countercurrent Multiplier System
Countercurrent flow and proximity allow descending and ascending limbs of Loop of Henle to interact in way that causes osmolality to build in medulla
Salt pumping in thick ascending part raises osmolality around descending limb, causing more H2O 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 Active Transport of salts, it causes even higher osmolality around descending limb (positive feedback)
Process repeats until equilibrium is reached when osmolality of medulla is 1400
17-43

44. Countercurrent Exchange in Vasa Recta
Is important component of countercurrent multiplier
Permeable to salt, H2O (via aquaporins), and urea
Recirculates salt, trapping some in medulla interstitial fluid
Reabsorbs H2O coming out of descending limb
Descending section has urea transporters
Ascending section has fenestrated capillaries
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45. The Role of Urea in Urine Concentration
Urea diffuses out of inner collect. duct into interstitial fluid in medulla
Urea then passes into ascend. limb so it recirculates in interstitial fluid in medulla
Water is reabsorbed by osmosis from collect. duct
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46. 17-46

47. Collecting Duct (CD) Plays important role in water conservation
Is impermeable to salt in medulla
Permeability to H2O depends on levels of ADH
17-47

48. Homeostasis of Plasma Concent. Maintained by ADH
Is secreted by post pituitary in response to dehydration
Stimulates insertion of aquaporins (water channels) into plasma membrane of Collect. Duct
When ADH is high, H2O is drawn out of CD by high osmolality of interstitial fluid
And reabsorbed by vasa recta
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49. Osmolality of Different Regions of the Kidney
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50. Renal Plasma Clearance
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51. Secretion is the Opposite of Reabsorption
The active transport of substances from the peritubular capillaries into the tubular fluid = secretion
Secretion is opposite in direction to that which occurs in reabsorption
Reabsorption decreases renal clearance; secretion increases renal clearance
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52. Renal Clearance Excretion rate =
(filtration rate + secretion rate) - reabsorption rate
17-52

53. Tubular Secretion of Drugs
Many drugs, toxins, and metabolites are secreted by membrane transporters in the Proximal Tubule
Major group of transporters involved is organic anion transporter (OAT)
Eliminate xenobiotics, therapeutic and abused drugs
Located in basolateral membrane of prox. Tubule
Larger xenobiotics elimin. by OATS in liver that transport into bile
Also some organic cation transporters that eliminate particular xenobiotics, such as nicotine
Considered polyspecific—overlapping specificity
17-53

54. Inulin Measurement of GFR
Inulin, a fructose polymer, is useful for measuring GFR because is neither reabsorbed or secreted
Rate at which a substance is filtered by the glomeruli can be calculated:
Quantity filtered = GFR x P
P = inulin concentration in plasma
Quantity excreted (mg/min) = V x U
V = rate of urine formation in ml/min; U = inulin concentration in urine in mg/ml
Amount filtered = amount excreted
GFR(ml/min) = V(ml/min) x U(mg/ml)
P(mg/ml)
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55. Renal Clearance of Inulin
17-55

56. Renal Plasma Clearance (RPC)
Is volume of plasma from which a substance is completely removed/min by excretion in urine
If substance is filtered but not reabsorbed then all filtered will be excreted RPC = GFR
If substance is filtered and reabsorbed then RPC < GFR
If substance is filtered but also secreted and excreted then RPC will be > GFR (=120 ml/ min)
RPC = V x U V= urine volume/min
P U= concent. of subst. in urine
P = concent. of subst. in plasma
17-56

57. Clearance of Urea Urea is freely filtered into glomerular capsule
Urea clearance calculations demonstrate how kidney handles a substance: RPC = V X U/P
V = 2ml/min; U = 7.5 mg/ml of urea; P = 0.2 mg/ml of urea
RPC = (2ml/min)(7.5mg/ml)/(0.2mg/ml) = 75ml/min
Urea clearance is 75 ml/min, compared to clearance of inulin (120 ml/min)
Thus 40-60% of filtered urea is always reabsorbed
Is passive process because of presence of carriers for facilitative diffusion of urea
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58. Measurement of Renal Blood Flow
Not all blood delivered to glomerulus is filtered into glomerular capsule
20% is filtered; rest passes into efferent arteriole and back into circulation
Substances that aren't filtered can still be cleared by active transport (secretion) into tubules
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59. Total Renal Blood Flow Using PAH
PAH clearance is used to measure total renal blood flow
Normally averages 625 ml/min
It is totally cleared by a single pass through a nephron
So it must be both filtered and secreted
Filtration and secretion clear only molecules dissolved in plasma
To get total renal blood flow, amount of blood occupied by erythrocytes must be taken into account
45% blood is RBCs; 55% is plasma
 total renal blood flow = PAH clearance
= 625/0.55 = 1.1L/min
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60. Total Renal Blood Flow Using PAH continued
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61. Glucose and Amino Acid Reabsorption
Filtered glucose and amino acids are normally 100% reabsorbed from filtrate
Occurs in Proximal Tubule by carrier-mediated cotransport with Na+
Transporter displays saturation if ligand concentration in filtrate is too high
Level needed to saturate carriers and achieve maximum transport rate is transport maximum (Tm)
Glucose and amino acid transporters don't saturate under normal conditions
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62. 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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63. Renal Control of Electrolyte and Acid-Base Balance
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64. Electrolyte Balance
Kidneys regulate levels of Na+, K+, H+, HCO3-, Cl-, and PO4-3 by matching excretion to ingestion
Control of plasma Na+ is important in regulation of blood volume and pressure
Control of plasma of K+ is important in proper function of cardiac and skeletal muscles
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65. Role of Aldosterone in Na+/K+ Balance
90% filtered Na+ and K+ reabsorbed before Distal Tub.
Remaining is variably reabsorbed in Distal Tub. and cortical Collect. Duct according to bodily needs
Regulated by aldosterone (controls K+ secretion and Na+ reabsorption)
In the absence of aldosterone, 80% of remaining Na+ is reabsorbed in Distal Tub. and cortical Collect. Duct
When aldosterone is high all remaining Na+ is reabsorbed
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66. K+ is Reabsorbed and Secretion
K+ almost completely reabsorbed in prox. tubule
Under aldosterone stim. secreted into cortical collect. Ducts
All K+ in urine from secretion rather than filtration
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67. Juxtaglomerular Apparatus (JGA)
Is specialized region in each nephron where afferent arteriole comes in contact with thick ascending limb LH
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68. 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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69. 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 and renal blood flow stimulate renin release
Via direct effects of BP on granular cells and by Symp activity initiated by arterial baroreceptor reflex
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70. 17-70

71. Macula Densa
Located where tubule cells make contact with granular cells
Acts as sensor for tubuloglomerular feedback; needed for autoreg. of GFR
Signals afferent arteriole to constrict
Signals granular cells to dec. secretion of renin when blood Na+ is inc.
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72. 17-72

73. Atrial Natriuretic Peptide (ANP)
Is produced by atria due to stretching of walls
An aldosterone antagonist
Stimulates salt and H2O excretion
Acts as an endogenous diuretic
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74. Relationship Between Na+, K+, and H+
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75. The Reabsorption of Na+ and Secretion of K+
In distal tubule, K+ and H+ secreted in response to potential difference prod. By reabsorption of Na+
High concent. of H+ may therefore dec. K+ secretion, and vice versa
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76. Renal Acid-Base Regulation
Kidneys help regulate blood pH by excreting H+ and/or reabsorbing HCO3-
Most H+ secretion occurs across walls of Proximal Tub. in exchange for Na+ (Na+/H+ antiporter)
Normal urine is slightly acidic (pH = 5-7) because kidneys reabsorb almost all HCO3- and excrete H+
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77. Reabsorption of HCO3- in PCT
Is indirect because apical membranes of PCT cells are impermeable to HCO3-
When urine acidic, bicarbonate combines with H+ to form carbonic acid
Carbonic acid in filtrate is converted to carbon dioxide and water in a reaction catalyzed by carbonic anhydrase (located in apical cell memb. of proximal tubule in contact with filtrate)
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78. Reabsorption of HCO3- in PCT continued
When urine is acidic, HCO3- combines with H+ to form H2CO3 (catalyzed by CA on apical membrane of PCT cells)
H2CO3 dissociates into CO2 + H2O
CO2 diffuses into PCT cell and forms H2CO3 (catalyzed by CA)
H2CO3 splits into HCO3- and H+ ; HCO3- diffuses into blood
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79. 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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80. Clinical Applications
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81. 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 H2O reabsorption in PCT when HCOs- is reabsorbed
Osmotic diuretics increase osmotic pressure of filtrate
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82. Sites of Action of Clinical Diuretics
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83. Kidney Diseases
In acute renal failure, ability of kidneys to excrete wastes and regulate blood volume, pH, and electrolytes is impaired
Rise in blood creatinine and decrease in renal plasma clearance of creatinine
Can result from atherosclerosis, inflammation of tubules, kidney ischemia, or overuse of NSAIDs
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84. 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 and resulting edema
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85. Kidney Diseases continued
In renal insufficiency, nephrons have been destroyed as a result of a disease
Clinical manifestations include salt and H2O retention and uremia (high plasma urea levels)
Uremia is accompanied by high plasma H+ and 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 and other wastes are removed
17-85