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176 Cards in this Set

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1. Normal arterial blood pH
[H+] = 40 nEq/L

pH = -log [0.00000004]

pH = 7.4
2. Normal venous blood pH

Why the difference?
pH = 7.35

B/c of the extra amounts of CO2 released from the tissues to form H2CO3 in these fluids
3. Intracellular pH
Usually slightly lower than plasma pH b/c the metabolism of the cells produces acid, especially H2CO3.

Can range from 6.0 to 7.4
4. pH of urine?

pH of gastric HCl?
Urine pH = 4.5-8.0

Gastric HCl pH = 0.8
5. Three primary systems that regulate the H+ concentration in the body to prevent acidosis or alkalosis
1. Chemical acid-base buffer systems of the body fluids
-reacts w/in seconds to minimize changes

2. Respiratory center
-reacts w/in a few minutes to eliminate CO2 and, therefore, H2CO3 form the body

3. Kidneys
-Slower to respond; takes hours to days, but are the most powerful of the acid-base regulatory systems.
6. Bicarbonate buffer system
Bicarbonate is the major buffer system in red blood cells (RBC)

In RBCs, carbonic anhydrase catalyzes the formation of carbonic acid, the major acid produced by the body

The dissociation of carbonic acid and protonation of bicarbonate acts as a buffer to prevent large changes in pH within RBCs.
7. Bicarbonate and hemoglobin in RBCs
CO2 generated by normal metabolism (TCA cycle) is released into the blood

RBCs take up CO2 and convert it to carbonic acid (H2CO3) via carbonic anhydrase

Carbonic acid dissociates into bicarbonate (HCO3−) and a proton (H+)

Hemoglobin absorbs protons and thereby buffers changes in pH because of histidine residues present within the hemoglobin molecule (pKa of 6.7)
8. Addition of a strong acid to the bicarbonate buffer system
1. Increased H+ is released from the acid and is buffered by HCO3-

2. As a result, more H2CO3 is formed, causing increased CO2 and H2O production.

3. The excess CO2 greatly stimulates respiration, which eliminates CO2 from the extracellular fluid.
9. Addition of a strong acid to the bicarbonate buffer system
1. OH- is released from the base and is buffered by H2CO3 to form additional HCO3-.

2. At the same time, the concentration of H2CO3 decreases (because it reacts with OH-), causing more CO2 to combine with H2O to replace the H2CO3.

3. The net result, therefore, is a tendency for the CO2 level in the blood to decrease, but the decreased CO2 levels in the blood inhibits respiration and decreases the rate of CO2 expiration.
10. Henderson-Hasselbalch equation
pH = pKa + log ([base]/[acid])

Used to describe the quantitative relationship between pH, pKa, and the concentrations of a weak acid and its conjugate base in an aqueous solution.

Can be used to calculate the ratio of the conjugate base to its un-dissociated weak acid at a given pH if the pKa is known

When pH=pKa, the dissociation of a weak acid is 50% (i.e. the concentration of the protonated form is equal to the concentration of the deprotonated form)
11. How does one use the Henderson-hasselbalch equation to calculate the pH of a solution if the molar concentration of HCO3- and the Pco2 are known?
pH = 6.1 + log [HCO3- / (0.03xPco2)]

(For the bicarbonate buffer system, the pK is 6.1)

-An increase in the HCO3- concentration causes the pH to rise, shifting the acid-base balance toward alkalosis

-An increase in Pco2 causes the pH to decrease, shifting the acid-base-balance toward acidosis
12. Where are the bicarbonate and Pco2 concentrations regulated?
The bicarbonate concentration is regulated by the kidneys, whereas the Pco2 in extracellular fluid is controlled by the rate of respiration
13. Metabolic acid-base disorder
Results from a primary change in extracellular fluid bicarbonate concentration
14. Respiratory acid-base disorder
Results from a primary change in Pco2 concentration
15. Effective pH range of the bicarbonate buffer system
pH = 5.1 - 7.1

Within one unit of 6.1
16. What determines the buffer power of a buffer system?
The buffer power is determined by the amount and relative concentrations of the buffer components.
17. What is the most important extracellular buffer?
Because of its effective pH range, the bicarb buffer system is the most important extracellular buffer in the body.
18. What is the importance of the phosphate buffer system?
Important in buffering renal tubular fluid and intracellular fluids
19. pKa of phosphate buffer system
pKa = 6.8; this allows the system to operate near its maximum buffering power in the normal pH of blood.
20. Two reasons why the phosphate buffer system is important in the renal tubular fluids
1. Phosphate usually becomes greatly concentrated in the tubules, thereby increasing the buffering power of the phosphate system

2. The tubular fluid usually has a considerably lower pH than the extracellular fluid does, bringing the operating range of the buffer closer to the pKa of the system (6.8)
21. Importance of the phosphate buffer system in intracellular fluids
The concentration of phosphate in the intracellular fluid is many times that in the extracellular fluid.

Also, the pH of intracellular fluid is lower than that of extracellular fluid and therefore is usually closer to the pKa of the phosphate buffer system
22. Consequence of the diffusion of CO2 through cell membranes
This diffusion of the elements of the bicarbonate buffer system causes the pH in intracellular fluid to change when there are changes in extracellular pH.

This is why the buffer systems within the cells help prevent changes in the pH of extracellular fluid, but may take several hours to become maximally effective.
23. Importance of intracellular proteins
Appox 60 to 70% of the total chemical buffering of the body fluids is inside the cells, and most of this results from the intracellular proteins

In addition, another factor that contributes to their buffering power is the fact that they pKas of many of these protein systems are fairly close to 7.4
24. What is the isohydric principle?
Whenever there is a change in H+ concentrations in the extracellular fluid, the balance of all the buffer systems changes at the same time.

The implication of this principle is that any condition that changes the balance of one of the buffer systems also changes the balance of all the others b/c the buffer systems actually buffer one another by shifting H+ back and forth between them.
25. Pulmonary expiration of CO2 does what?
It balances the metabolic formation of CO2 .

If the rate of metabolic formation of CO2 increases, the Pco2 of the extracellular fluid is likewise increased.

A decreased metabolic rate lowers the Pco2.

If the rate of pulmonary ventilation is increased, CO2 is blown off from the lungs, and the Pco2 in the extracellular fluid decreases.
26. Increasing alveolar ventilation does what?
Decreases the extracellular fluid hydrogen ion concentration and raises pH

The higher the alveolar ventilation, the lower the Pco2; conversely, the lower the alveolar ventilation rate, the higher the Pco2.

When CO2 concentration increases, the H2Co3 concentration and H+ concentration also increases, thereby lowering extracellular fluid pH.
27. Increased hydrogen ion concentration stimulates what?
It stimulates alveolar ventilation.

Not only does the alveolar ventilation rate influence H+ concentration by changing the Pco2 of the body fluids, but the H+ concentration affects the rate of alveolar ventilation.
28. Effect of blood pH on the rate of alveolar ventilation
The change in ventilation rate per unit pH change is much greater at reduced levels of pH compared with increased levels of pH.

The reason for this is that as the alveolar ventilation rate decreases, owing to an increase in pH, the amount of oxygen added to the blood decreases and the partial pressure of oxygen in the blood also decreases, which stimulates the ventilation rate.

Therefore, the respiratory compensation for an increase in pH is not nearly as effective as the response to a marked reduction in pH.
29. Feedback control of H+ concentration by the respiratory system
B/c increased H+ concentration stimulates respiration, and because increased alveolar ventilation decreases the H+ concentration, the respiratory system acts as a typical negative feedback controller of H+ concentration.

↑[H+] ⇒ ↑Alveolar ventilation

↑Alveolar ventilation ⇒ ↓Pco2

↓Pco2 ⇒ ↓[H+]
30. What is the efficiency of respiratory control of hydrogen ion concentration?
Respiratory control cannot return the H+ concentration all the way back to normal when a disturbance outside the respiratory system has altered pH.

The respiratory system has an effectiveness between 50 and 75%; corresponding to a feedback gain of 1 to 3.

That is, if the H+ concentration is suddenly increased by adding acid to the extracellular fluid and pH fall from 7.4 to 7.0, the respiratory system can return the pH to a value of about 7.2 to 7.3. This response occurs within 2-12 minutes.
31. Buffering power of the respiratory system
Respiration regulation of acid-base balance is a physiologic type of buffer system b/c it acts rapidly and keeps the H+ concentration from changing too much until the slowly responding kidneys can eliminate the imbalance.

One to two times as much acid or base can normally be buffered by this mechanism as by the chemical buffers.
32. Respiratory acidosis due to impaired lung function
Abnormalities of respiration can also cause changes in H+ concentration; for example, an impairment of lung function decreases the ability of the lungs to eliminate CO2; this causes a buildup of CO2 and a tendency towards respiratory acidosis.

Also, the ability to respond to metabolic acidosis is impaired b/c the compensatory reductions in PCo2 that would normally occur by means of increased ventilation are blunted.
33. Renal control of acid-base balance
The kidneys control acid-base balance by excreting either an acidic or basic urine.
34. Mechanism of kidney excretion of acids or bases
1. Large numbers of HCO3- are filtered continuously and if they are excreted into the urine, bases are removed from the blood.

2. Large numbers of H+ are also secreted into the tubular lumen by the tubular epithelial cells, thus removing acid from the blood.

3. If more H+ is secreted than HCO3- if filtered, there will be a net loss of acid from the extracellular fluid.

4. Conversely, if more HCO3- is filtered than H+ is secreted, there will be a net loss of base.
35. How do kidneys regulate extracellular fluid H+ concentration?

3 fundamental mechanisms...
Through three fundamental mechanisms:

1. Secretion of H+
2. Reabsorption of filtered HCO3-
3. Production of new HCO3-
36. Where does hydrogen ion secretion and bicarbonate reabsorption occur?
In virtually all parts of the tubules except the descending and ascending thin limbs of the loop of Henle.

About 80-90% of the bicarbonate reabsorption occurs in the proximal tubule, so that only a small amount of bicarbonate flows into the distal tubules and collecting ducts.

In the thick ascending loop of Henle, another 10% of the filtered bicarbonate is reabsorbed and the remainder of the reabsorption takes place in the distal tubule and collecting duct.

For each bicarbonate reabsorbed, a tubular secretion of H+ must occur.
37. Where does the secondary active transport of hydrogen ions occur?
The epithelial cells of the proximal tubule, the thick segment of the ascending loop of Henle, and the early distal tubule all secrete H+ into the tubular fluid by sodium-hydrogen counter-transport.

This secondary active secretion of H+ is coupled with the transport of Na into the cell at the luminal membrane by the sodium-hydrogen exchanger protein, and the energy for H+ secretion against a concentration gradient is derived from the sodium gradient favoring Na movement into the cell.

This gradient is established by the sodium-potassium ATPase pump in the basolateral membrane.

More than 90% of the bicarbonate is reabsorbed in this manner, required large amounts of H+ to be secreted each day by the tubules.
38. Process of H+ secretion and bicarbonate reabsorption
1. Active secretion of H+ into the renal tubule
2. Tubular reabsorption of bicarbonate ions by combination with H+ to form carbonic acid, which dissociates to form CO2 and water.
3. Sodium ion reabsorption in exchange for H+ secreted

This patten of H+ secretion occurs in the proximal tubule, the thick ascending segment of the loop of Henle, and the early distal tubule.
39. Net result of hydrogen secretion and bicarbonate reabsorption in the kidneys
For every H+ secreted into the tubular lumen, an HCO3- enters the blood.
40. Can the bicarbonate ions permeate the luminal membranes of the tubular cells?
Bicarbonate ions do not readily permeate the luminal membranes of the renal tubular cells.

Therefore, the HCO3- that is filtered by the glomerulus cannot be directly reabsorbed.
41. How are filtered bicarbonate ions reabsorbed by the tubules?
Uses carbonic anhydrase

1. First, the bicarbonate ion must combine with a H+ to generate H2CO3.
2. The H2CO3 formed then dissociates into CO2 and H2O.
3. The CO2 can then move easily across the tubular membrane; therefore, it instantly diffuses into the tubular cell, where it recombines with H2O under the influence of carbonic anhydrase, to generate a new H2CO3 molecule.
4. This H2CO3 in turn dissociates to form HCO3- and H+
5. The HCO3- then diffuses thru the basolateral membrane into the interstitial fluid and is taken up into the peritubular capillary blood.
42. What two processes facilitate the transport of HCO3 across the basolateral membrane?
1. Na+_HCO3- co-transport

2. Cl-_HCO3- exchange
43. Net result of hydrogen secretion and bicarbonate reabsorption (revised)
Each time an H+ is formed in the tubular epithelial cells, an HCO3- is also formed and released back into the blood.

The net effect of these reactions is the reabsorption of HCO3- from the tubules, although the HCO3- that actually enters the extracellular fluid is not the same as that filtered into the tubules.
44. Titration of bicarbonate ions
In metabolic alkalosis, the excess HCO3- cannot be reabsorbed; therefore, the excess HCO3- is left in the tubules and eventually excreted into the urine.

In metabolic acidosis, there is excess H+ relative to HCO3-, causing complete reabsorption of the bicarbonate; the excess H+ passes into the urine.

Thus, the basic mechanism by which the kidneys correct either acidosis or alkalosis is incomplete titration of H+ of HCO3-; leaving one or the other to pass into the urine and be removed from the extracellular fluid.
45. Where does primary active secretion of H+ occur?
Beginning in the late distal tubules and continuing thru the remainder of the tubular system, the tubular epithelium secreted H+ by primary active transport.

H+ is transported directly across the luminal membrane of the tubular cell by a specific protein, a hydrogen-transporting ATPase. (Uses ATP for pumping H+)

The primary active secretion of H+ occurs in a special type of cell called the intercalated cells of the late distal tubule and in the collecting tubules
46. Mechanism of primary active secretion of H+
1. The dissolved CO2 in the cell combines with H2O to form H2CO3
2. The H2CO3 then dissociates into HCO3-, which is reabsorbed into the blood, plus H+, which is secreted into the tubule by means of the hydrogen ATPase mechanism

For each H+ secreted, an HCO3- is reabsorbed, similar to the process in the proximal tubules.
47. Whats the difference between H+ secretion and HCO3- reabsorption in this later part of the nephron?
The main difference is that H+ moves across the luminal membrane by an active H+ pump instead of by counter-transport, as occurs in the early parts of the nephron
48. Significant importance of the later part of the nephron
This mechanism is important in forming a maximally acidic urine.

In the proximal tubules, H+ concentration can only be increased about 3-4x; in the distal collecting tubules, the H+ concentration can be increased as much as 900x
49. What happens where there's an excess of H+ in the urine?
The H+ combines with buffers other than HCO3- and this results in the generation of new HCO3- that can also enter the blood.

Thus, when there is excess H+ in the extracellular fluid, the kidneys not only resorb all the filtered HCO3-, but also generate new HCO3-, thereby helping to replenishing the HCO3- lost form the extracellular fluid in acidosis.
50. What is the phosphate buffer system?
Composed of HPO4- and H2PO4-. Both become concentrated in the tubular fluid b/c of their relatively poor reabsorption and b/c of the reabsorption of water from the tubular fluid.

Therefore, although phosphate is not an important extracellular fluid buffer, it is much more effective as a buffer in the tubular fluid.

The one difference between this buffer system and the bicarbonate system is that the HCO3- that is generated in the tubular cell and enters the peritubular blood represents a net gain of HCO3- by the blood, rather than merely a replacement of filtered HCO3-.
51. What is the ammonia buffer system?
This is a second buffer system in the tubular fluid that is even more important quantitatively than the phosphate buffer system.

Composed of ammonia and ammonium ion.

Ammonium ion is synthesized from glutamine, which breaks down to form two ammonium ions and two HCO3-.

Thus, for each molecule of glutamine metabolized in the proximal tubules, 2 NH4+ are secreted into the urine and 2 HCO3- are reabsorbed into the blood.

The HCO3- generated by this process constitutes new bicarbonate as well.
52. Mechanism of NH4+ addition to the tubular fluids
H+ is secreted by the tubular membrane into the lumen, where it combines with NH3 to form NH4+, which is then excreted.

The collecting ducts are permeable to NH3, which can easily diffuse into the tubular lumen.

However, the luminal membrane of this part of the tubules is much less permeable to NH4+; therefore, once the H+ has reacted with NH3 to form NH4+, the NH4+ is trapped in the tubular lumen and eliminated in the urine.

For each NH4+ excreted, a new HCO3- is generated and added to the blood.
53. Chronic acidosis and NH4+ excretion
With chronic acidosis, the dominant mechanism by which acid is eliminated is excretion of NH4+.

Thus, chronic acidosis increases NH4+ excretion which also generates new bicarbonate.
54. How does one determine the amount of bicarb excreted in the urine?
Urine flow rate multiplied by urinary bicarbonate concentration

This number indicates how rapidly the kidneys are removing HCO3- from the blood
55. Determining the amount of new bicarbonate contributed to the blood at any given time
Calculated by measuring NH4+ excretion

(urine flow rate multiplied by urinary NH4+ concentration)
56. What is the titratable acid?
This is the value that is used to determine the amount of the nonbicarbonate, non-NH4+ buffer excreted in the urine.

The amount of titratable acid in the urine is measured by titrating the urine with a strong base to a pH of 7.4, the pH of normal plasma. This titration reverses the events that occurred in the tubular lumen when the tubular fluid was titrated by excreted H+. Therefore, teh number of mEq of NaOH required to return the urinary pH to 7.4 equals the number of mEq of H+ added to the tubular fluid that combined with phosphate and other organic buffers.
57. Net acid excretion
Net acid excretion =

(NH4+ excretion + urinary titratable acid - Bicarbonate excretion)
58. What are the two most important stimuli for increasing H+ secretion by the tubules in acidosis?
The most important stimuli for increasing H+ secretion by the tubules in acidosis are:

1. An increase in Pco2 of the extracellular fluid

2. An increase in H+ concentration of the extracellular fluid (decreased pH)
59. Excessive aldosterone secretion can do what to H+ secretion?
Increases H+ secretion into the tubular fluid, and thus, increased amounts of bicarbonates added to the blood.

Causes alkalosis
60. Increased Angiotensin II
Also increases H+ secretion and HCO3- reabsorption
61. Extracellular fluid volume depletion
Stimulates sodium reabsorption by the renal tubules and increases H+ secretion and HCO3- reabsorption

Causes alkalosis
62. In what two ways does extracellular fluid volume depletion causes increased secretion of H+?
1. Increased angiotensin II levels, which directly stimulate the activity of the Na+_H+ exchanger in the renal tubules

2. Increased aldosterone levels, which stimulate H+ secretion by the intercalated cells of the cortical collecting tubules.
63. 6 factors that increase H+ secretion and HCO3- reabsorption
1. ↑Pco2

2. ↑H+, ↓HCO3-

3. ↓Extracellular fluid volume

4. ↑Angiotensin II

5. ↑Aldosterone

6. Hypokalemia
64. 6 factors that decrease H+ secretion and HCO3- reabsorption
1. ↓Pco2

2. ↓H+, ↑HCO3-

3. ↑Extracellular fluid volume

4. ↑Angiotensin II

5. ↓Aldosterone

6. Hyperkalemia
65. Primary compensation for metabolic acidosis
↑ Ventilation rate to reduce Pco2
66. Primary compensation for respiratory acidosis
↑ Plasma HCO3- concentration by the kidneys
67.Primary compensation for metabolic alkalosis
↓ Ventilation rate to raise Pco2
68. Primary compensation for respiratory alkalosis
↓ Plasma HCO3- concentration by the kidneys caused by increased renal excretion of HCO3-
69. What can cause respiratory alkalosis?
1. Person ascending to a high altitude
2. Hyperventilation
70. What are 6 things that can cause metabolic acidosis?
1. Renal tubular acidosis
-defect in renal secretion of H+ or in reabsorption of HCO3- or both

2. Diarrhea
-loss of large amounts of sodium bicarbonate into the feces

3. Vomiting of intestinal contents
-deep GI vomiting causes loss of bicarbonate

4. Diabetes mellitus
-high blood acetoacetic acid levels

5. Ingestion of acids
-aspirin

6. Chronic renal failure
71. What can cause respiratory acidosis?
Pathological conditions that damage the respiratory centers or that decrease the ability of the lungs to eliminate CO2

This includes pneumonia, emphysema, etc...
72. What 4 things can cause metabolic alkalosis?
1. Administration of diuretics (except the carbonic anhydrase inhibitors)
-all diuretics cause increased flow of fluid along the tubules, which leads to increased resorption of Na+ which is coupled with H+ excretion

2. Excess aldosterone

3. Vomiting of gastric contents
-Lose HCl

4. Ingestion of alkaline drugs
-Tums
73. Treatment of acidosis
1. PA administration of Sodium bicarbonate

2. IV administration of sodium lactate and sodium gluconate

*careful not to infuse sodium bicarbonate via IV b/c of potentially dangerous side effects
74. Treatment of alkalosis
1. PO administration of ammonium chloride
-liberates HCl in the body

2. Lysine monohydrochloride
75. Expected values for a simple respiratory acidosis
↓ plasma pH

↑ Pco2

↑ plasma concentration of HCO3- after partial renal compensation
76. Expected values for a simple metabolic acidosis
↓ plasma pH

↓ plasma concentration of HCO3-

↓ Pco2 after partial respiratory compensation
77. Expected values for a simple respiratory alkalosis
↑ plasma pH

↓ Pco2

↓ plasma concentration of HCO3-
78. Expected values for a simple metabolic alkalosis
↑ plasma pH

↑ plasma concentration of HCO3-

↑ Pco2
79. Mixed acid-base disorder
In some instance, acid-base disorders are not accompanied by appropriate compensatory responses.

Thus, there are two or more underlying causes for the acid-base disturbance
80. What is an anion gap?
The difference between unmeasured anions and unmeasured cations.

Will increase if unmeasured anions rise or if unmeasured cations fall.

***Used mainly in diagnosing different causes of metabolic acidosis.***
81. 7 causes of increased anion gap (Normochloremia) in metabolic acidosis
1. Diabetes mellitus (ketoacidosis)
2. Lactic acidosis
3. Chronic renal failure
4. Aspirin poisoning
5. Methanol poisoning
6. Ethylene glycol poisoning
7. Starvation
82. 4 causes of normal anion gap (Hyperchloremia) in metabolic acidosis
1. Diarrhea
2. Renal tubular acidosis
3. Carbonic anhydrase inhibitors
4. Addison's disease
83. What is hyperchloremic metabolic acidosis?
If the plasma [Cl-] increases in proportion to the fall in plasma [HCO3-], the anion gap will remain normal but HCO3- has been effectively replaced by Cl-
84. How does one calculate the anion gap?
[Na] - [HCO3-] - [Cl-]

Positives minus the negatives
85. What is a diuretic?
A diuretic is a substance that increases the rate of urine volume output.

Most diuretics also increase urinary excretion of solutes, especially sodium and chloride.

In fact, most diuretics that are used clinically act by decreasing the rate of sodium reabsorption from the tubules, which causes natriuresis, which in turn causes diuresis.
86. How do diuretics cause increased water output?
In most cases, increased water output occurs secondary to inhibition of tubular sodium reabsorption, because sodium remaining in the tubules acts osmotically to decrease water reabsorption.

B/c the renal tubular reabsorption of many solutes, such as potassium, chloride, magnesium, and calcium, is also influenced secondarily by sodium reabsorption, many diuretics raise renal output of these solutes as well.
87. Length of time a diuretic works
Some diuretics can increase urine output more than 20x within a few minutes after they are administered.

However, the effect of most diuretics on renal output of salt and water subsides within a few days.

This is due to other compensatory mechanisms initiated by the decreased ECF volume.

For example, a decreased ECF often reduces arterial pressure and GFR and increases renin secretion and angiotensin II formation. All these responses, together, eventually override the chronic effects of the diuretic on urine output.
88. How do osmotic diuretics decrease water reabsorption?
Osmotic diuretics decrease water reabsorption by increasing osmotic pressure of tubular fluid.

Injection into the blood stream of substances that are not easily reabsorbed by the renal tubules, such as urea, mannitol, and sucrose, causes a marked increase in the concentration of osmotically active molecules in the tubules. The osmotic pressure of these solutes then greatly reduces water reabsorption, flushing large amounts of tubular fluid into the urine.
89. How do loop diuretics work?
Furosemide, ethacrynic acid, and bumetanide are powerful loop diuretics that decrease active reabsorption in the thick ascending limb of the loop of Henle by blocking the 1-sodium, 2-chloride, 1-potassium co-transporter located in the luminal membrane of the epithelial cells.

These diuretics are among the most powerful of the clinically used diuretics.
90. What are the 2 reasons for loop diuretics raising urine output of Cl, Na, K, and other electrolytes as well as water?
1. They greatly increase the quantities of solutes delivered to the distal parts of the nephrons, and these act as osmotic agents to prevent water reabsorption as well.

2. They disrupt the countercurrent multiplier system by decreasing absorption of ions from the loop of Henle into the medullary interstitium, thereby decreasing the osmolarity of the medullary interstitial fluid. B/c of this effect, loop diuretics impair the ability of the kidneys to either concentrate or dilute the urine.
91. Why is urinary dilution impaired with loop diuretics?
Urinary dilution is impaired b/c the inhibition of sodium and chloride reabsorption in the loop of Henle causes more of these ions to be excreted along with increased water excretion.
92. Why is urinary concentration impaired with loop diuretics?
Urinary concentration is impaired b/c the renal medullary interstitial fluid concentration of these ions, and therefore renal medullary osmolarity, is reduced.

Consequently, reabsorption of fluid from the collecting ducts is decreased, so that the maximal concentrating ability of the kidneys is also greatly reduced.
93. Loop diuretic summary
B/c of these multiple effects, 20-30% of the glomerular filtrate may be delivered into the urine, causing, under acute conditions, urine output to be as great as 25x normal for at least a few minutes.
94. How do thiazide diuretics work?
Thiazide diuretics inhibit NaCl reabsorption in the early distal tubule.

The thiazide derivatives, such as chlorothiazide, act mainly on the early distal tubules to block the NaCl co-transporter in the luminal membrane of the tubular cells.

Under favorable conditions, these agents cause 5-10% of the glomerular filtrate to pass into the urine. This is about the same amount of sodium normally reabsorbed by the distal tubules.
95. How do carbonic anhydrase inhibitors work?
Carbonic anhydrase inhibitors block sodium-bicarbonate reabsorption in the proximal tubules.
96. Acetazolamide
Acetazolamide inhibits the enzyme carbonic anhydrase, which is critical for the reabsorption of bicarb in the *proximal tubule.*
97. Where is carbonic anhydrase located?
Carbonic anhydrase is abundant in the proximal tubule, the primary site of action of carbonic anhydrase inhibitors. Some carbonic anhydrase is also present in other tubular cells, such as the intercalatated cells of the collecting tubule.
98. How and why is sodium reabsorption decreased with carbonic anhydrase inhibitors?
B/c hydrogen ion secretion and bicarb reabsorption in the proximal tubules are couples to sodium reabsorption through the sodium-hydrogen ion counter-transport mechanism in the luminal membrane, decreasing bicarb reabsorption also reduces sodium reabsorption.

The blockage of sodium and bicarb reabsorption from the tubular fluid causes these ions to remain int he tubules and act as an osmotic diuretic.
99. What is a disadvantage of the carbonic anhydrase inhibitors?
They cause some degree of acidosis b/c of the excessive loss of bicarb in the urine.
100. How do competitive inhibitors of aldosterone work?
Competitive inhibitors of aldosterone decrease sodium reabsorption from and potassium secretion into the cortical collecting tubule.
101. Spironolactone and eplerenone are....
Spironolactone and eplerenone are aldosterone antagonists that compete with aldosterone for receptor sites in the cortical collecting tubule epithelial cells and, therefore, can decrease the reabsorption of sodium and secretion of potassium in this tubular segment.

As a consequence, sodium remains in the tubules and acts as an osmotic diuretic, causing increased excretion of water as well as sodium.
102. How are adosterone inhibitors potassium sparing diuretics?
B/c these drugs also block the effect of aldosterone to promote potassium secretion in the tubules, they decrease the excretion of potassium.

Aldosterone antagonists also cause movement of potassium from the cells to the ECF. In some instances, this causes the ECF potassium concentration to increase excessively.

For this reason, spironolactone and other aldosterone inhibitors are referred to as potassium sparing diuretics.
103. Amiloride and triamterene are...?
Amiloride and triamterene also inhibit sodium reabsorption and potassiium secretion in the collecting tubules, similar to the effects of spironolactone.

However, at the cellular level, these drugs act directly to block the entry of sodium into the sodium channels of the luminal membrane of the collecting tubule epithelial cells. B/c of this decreased sodium entry into the epithelial cells, there is also decreased sodium transport across the cells' basolateral membranes and, therefore, decreased activity of the sodium-potassium ATP pump.
104. How are sodium channel blockers also potassium sparing diuretics?
The decreased activity of the sodium-potassium ATP pump reduces the transport of sodium into the cells and ultimately decreases the secretion of potassium into the tubular fluid.

For this reason, the sodium channel blockers are also potassium sparing diuretics and decrease the urinary excretion rate of potassium.
105. What are the two main categories of severe kidney disease?
1. Acute renal failure, in which the kidneys abruptly stop working entirely or almost entirely but may eventually recover nearly normal function

2. Chronic renal failure, in which there is progressive loss of function of more and more nephrons that gradually decreases overall kidney function.
106. What are the three main categories of causes for acute renal failure?
1. Acute renal failure resulting from decreased blood supply to the kidneys; this condition is often referred to as prerenal acute renal failure - can be a consequence of heart failure with reduced cardiac output and low BP

2. Intrarenal acute renal failure resulting from abnormalities within the kidney itself, including those that affect the blood vessels, glomeruli, or tubules.

3. Postrenal acute renal failure, resulting from obstruction of the urinary collecting system anywhere from the calyces to the outflow from the bladder. Common causes are kidney stones.
107. Prerenal acute renal failure is caused by...?
Caused by decreased blood flow to the kidney.

The main purpose of high blood flow to the kidneys is to provide enough plasma for the high rates of glomerular filtration needed for effective regulation of body fluid volumes and solute concentration.

Therefore, decreased renal blood flow is usually accompanied by decreased GFR and decreased urine output of water and solutes.
108. How can acute renal failure be reversed?
As long as renal blood flow does not fall below about 20-25% normal, acute renal failure can ususally be reversed if the cause of the ischemia is corrected before damage to the renal cells has occurred.

Unlike some tissues, the kidney can endure a relatively large reduction in blood flow before actual damage to the renal cells occurs.
109. Reason for kidney being able to endure a large reduction in blood flow
As renal blood flow is reduced, the GFR and the amount of sodium chloride filtered by the glomeruli are reduced.

This decreases the amt of sodium chloride that must be reabsorbed by the tubules, which uses most of the energy and oxygen consumed by the normal kidney. Therefore, as renal blood flow and GFR fall, the requirement for renal oxygen consumption is also reduced.

As the GFR approaches zero, oxygen consumption of the kidney approaches the rate that is required to keep the renal tubular cells alive even when they are not reabsorbing sodium.
110. What happens when blood flow is less than 20-25x the normal renal blood flow?
When blood flow is reduced below this basal requirement, the renal cells start to become hypoxic and further decreases in renal blood flow, if prolonged, will cause damage or even death of the renal cells, especially the tubular epithelial cells.

If the cause of the prerenal acute renal failure is not corrected and ischemia persists longer than a few hours, it can lead to intrarenal acute renal failure.
111. Intrarenal acute renal railure
Abnormalities that originate within the kidney and that abruptly diminish urine output fall into the general category of intrarenal acute renal failure.
112. What are the three categories of acute renal failure?
1. Conditions that injure the glomerular capillaries or other small renal vessels

2. Conditions that damage the renal tubular epithelium

3. Conditions that cause damage to the renal interstitium.
113. Glomerulonephritis and acute renal failure
Acute glomerulonephritis is a type of intrarenal acute renal failure usually caused by an abnormal immune reaction that damages the glomeruli.

It is related to infections caused by a certain type of group A beta streptococci.

It is not the infection that damages the kidneys.

Instead, over a few weeks, as antibodies develop against the stretococcal antigen, the antibodies develop against the streptococcal antigen, the antibodies and antigen react with each other to form an insoluble immune complex that becomes entrapped in the glomeruli, especially in the basement membrane portion of the glomeruli.
114. What happens once the immune complex has deposited in the glomeruli?
Many of the cells of the glomeruli begin to proliferate, but mainly the mesangial cells that lie between the endothelium and the epithelium.

In addition, large numbers of WBCs become entrapped in the glomeruli. Many of the glomeruli become blcoked by this inflammatory reaction, and those that are not blocked ususally become excessively permeable, allowing both protein and RBCs to leak from the blood of the glomerular capillaries into the glomerular filtrate.

In severe cases, either total or almost complete renal shutdown occurs.
115. How long does the acute inflammation of the glomeruli last?
The acute inflammation of the glomeruli usually subsides in about 2 weeks, and in most patients, the kidneys return to almost normal function within the next few weeks to few months.

Sometimes, however, many of the glomeruli are destroyed beyond repair, and in a small percentage of patients, progressive renal deterioration continues indefinitely, leading to chronic renal failure.
116. Tubular necrosis as a cause of acute renal failure
Another cause of intrarenal acute renal failure is tubular necrosis, which means destruction of epithelial cells in the tubules.
117. What are two common causes of tubular necrosis?
1. Severe ischemia and inadequate supply of oxygen and nutrients to the tubular epithelial cells

2. Poisons, toxins, or medications that destroy the tubular epithelial cells
118. Acute tubular necrosis caused by severe renal ischemia
Severe ischemia of the kidney can result from circulatory shock or another other disturbance that severely impairs the blood supply to the kidney. If the ischemia is severe enough to seriously impair the delivery of nutrients and oxygen to the renal tubular epithelial cells, and if the insult is prolonged, damage or eventual destruction of the epithelial cells can occur.

When this happens, tubular cells lough off and plug many of the nephrons, so that there is not urine output from the blocked nephrons; the affected nephrons often fail to excrete urine even when renal blood flow is restored to normal, as long as the tubules remain plugged.
119. What are the most common causes of ischemic damage to the tubular epithelium?
The most common causes of ischemic damage to the tubular epithelium are the prerenal causes of acute renal failure associated with circulatory shock.
120. Acute tubular necrosis caused by toxins or medications
Some of these are carbon tetrachloride, heavy metals, ethylene glycol, various insecticides, various medications used as antibiotics, and cis-platinum.

Each of these substances has a specific toxic action on the renal tubular epithelial cells, causing death of many of them. As a result, the epithelial cells slough away from the basement membrane and plug the tubules. In some instances, the basement membrane also is destroyed. If the basement membrane remains intact, new tubular epithelial cells can grow along the surface of the membrane, so that the tubule repairs itself within 10-20 days.
121. Postrenal acute renal failure caused by abnormalities of the lower urinary tract
Multiple abnormalities of the lower urinary tract can block or partially block urine flow and therefore lead to acute renal failure even when the kidney's blood supply and other functions are initially normal.

Chronic obstruction of the urinary tract, lasting for several days or weeks, can lead to irreversible kidney damage.
122. What are some causes of postrenal acute kidney failure?
1. Bilateral obstruction of the ureters or renal pelvises caused by large stones or blood clots
2. Bladder obstruction
3. Obstruction of the urethra
123. What are the major physiologic effects of acute renal failure?
A major physiologic effect of acute renal failure is retention in the blood and extracellular fluid of water, waste products of metabolism, and electrolytes. This can lead to water and salt overload, which in turn can lead to edema and hypertension.

Excessive retention of potassium, however, is often a more serious threat to patients with acute renal failure, b/c hyperkalemia can be fatal.

B/c the kidneys are also unable to excrete sufficient hydrogen ions, patients with acute renal failure develop metabolic acidosis, which in itself can be lethal or can aggravate the hyperkalemia.
124. Chronic renal failure
Chronic renal failure results from progressive and irreversible loss of large numbers of functioning nephrons. Serious clinical symptoms often do not occur until the number of functional nephrons falls to at least 70-75% below normal.

In general, chronic renal failure can occur b/c of disorders of the blood vessels, glomeruli, tubules, renal interstitium, and lower urinary tract.

The end result is essentially the same - decrease in the number of functional nephrons.
125. End stage renal disease
In many cases, an inital insult to the kidney leads to progressive deterioration of kidney function and further loss of nephrons to the point where the person must be placed on dialysis treatment or transplanted with a functional kidney to survive. This condition is referred to as end-stage renal disease.
126. What is the vicious circle of chronic renal failure?
Loss of nephrons because of disease may increase pressure and flow in the surviving glomerular capillaries, which in turn may eventually injure these "normal" capillaries as well, thus causing progressive sclerosis and eventual loss of these glomeruli.
127. Sclerotic lesions in renal disease
These sclerotic lesions can eentually obliterate the glomerulus, leading to further reduction in kidney function, further adaptive changes in the remaining nephrons, and a slowly progressing vicious circle that eventually terminates in end-stage renal disease.
128. What is the only proven method of slowing down the progressive loss of kidney function in end-stage renal disease?
Only way is to lower arterial pressure and glomerular hydrostatic pressure, especially by using drugs such as angiotensin-converting enzyme inhibitors or angiotensin II antagonists.
129. What are the four most common causes of end stage renal disease?
Glomerulonephritis
Diabetes
Hypertension
Polycystic kidney disease
130. What 3 types of vascular lesions can lead to ischemia and death of kidney tissue?
1. Atherosclerosis of the larger renal arteries, with progressive sclerotic constriction of the vessels

2. Fibromuscular hyperplasia of one or more of the large arteries, which also causes occlusion of the vessels

3. Nephrosclerosis caused by sclerotic lesions of the smaller arteries, arterioles, and glomeruli.
131. What is benign nephrosclerosis?
Benign nephrosclerosis is the most common form of kidney disease and is seen at least some extent in about 70% of postmortem exams in people who die after teh age of 60.

This type of vascular lesion occurs in the smaller interlobular arteries and in the afferent arterioles of the kidney. It is believed to begin with the leakage of plasma through the intimal membrane of these vessels. This causes fibrinoid deposits to develop in the medial layers of these vessels, followed by progressive thickening of the vessel wall that eventually constricts the vessels, and in some cases, occludes them.

Therefore, much of the kidney tissue becomes replaced by small amounts of fibrous tissue.
132. Prevalence of nephrosclerosis and glomerulosclerosis
Nephrosclerosis and glomerulosclerosis occur to some extent in most people after the foruth decade of life, causing about 10% decrease in the number of functional nephrons each 10 years after age 40.

This loss of glomeruli and overall nephron function is reflected by a progressive decrease in both renal blood flow and GFR.

Even in normal people, kidney plasma flow and GFR decrease by 40-50% by age 80.
133. What can increase the frequency and severity of nephrosclerosis and glomerulosclerosis?
The frequency and severity of nephrosclerosis and glomerulosclerosis are greatly increased by concurrent hypertension or diabetes.

In fact, DM and hypertension are the two most important causes of end-stage renal disease.
134. What is malignant nephrosclerosis?
Benign nephrosclerosis in association with severe hypertension can lead to a rapidly progressing malignant nephrosclerosis.

The characteristic histological features of malignant nephrosclerosis include large amounts of fibrinoid deposits in the arterioles and progressive thickening of the vessels, with severe ischemia occurring in the affected nephrons.
135. What is chronic glomerulonephritis?
In contrast to the acute form, chronic glomerulonephritis is a slowly progressive disease that often leads to irreversible renal failure. It may be primary kidney disease, following acute glomerulonephritis, or it may be secondary to systemic diseases, such as SLE.
136. How does chronic glomerulonephritis form?
In most cases, chronic glomerulonephritis begins with accumulation of precipitated antigen-antibody complexes in the glomerular membrane.

The results of the accumulation of antigen-antibody complex in the glomerular membranes are inflammation, progressive thickening of the membranes and eventual invasion of the glomeruli by fibrous tissue.

In later stages of the disease, the glomerular capillary filtration coefficient becomes greatly reduced b/c of decreased numbers of filtering capillaries in the glomerular tufts and b/c of thickened glomerular membranes.
137. What is interstitial nephritis?
Primary or secondary disease of the renal interstitium is referred to as interstitial nephritis.

In general this can result from vascular, glomerular, or tubular damage that destroys individual nephrons, or it can involve primary damage to the renal interstitium by poisons, drugs, and bacterial infections.
138. What is pyelonephritis?
Renal interstitial injury caused by bacterial infection is called pyelonephritis. The infection can result from different types of bacteria but especially from E. coli that originate from fecal contamination of the urinary tract.

These bacteria reach the kidneys either by way of the blood stream or, more commonly, by ascension from the lower urinary tract by way of the ureters to the kidneys.
139. What are the 2 general clinical conditions that may interfere with the normal flushing of bacteria from the bladder?
1. The inability of the bladder to empty completely, leaving residual urine in the bladder

2. The existence of obstruction of urine outflow. Can result form cystitis.
140. What is vesicoureteral reflux?
Once cystitis has occurred, it may remain localized w/o ascending to the kidney, or in some people, bacteria may reach the renal pelvis b/c of a pathological condition in which urine is propelled up on one or both of the ureters during micturition.

As a result, some of the urine is propelled upward toward the kidney, carrying with it bacteria that can reach the renal pelvis and renal medulla, where they can initiate the infection and inflammation associated with pyelonephritis.
141. What is the progression of pyelonephritis?
Pyelonephritis begins in the renal medulla and therefore usually affects the function of the medulla more than it affects the cortex, at least in the initial stages.

B/c one of the primary functions of the medulla is to provide the countercurrent mechanism for concentrating urine, patients with pyelonephritis freq have markedly impaired ability to concentrate the urine.
142. What is long standing pyelonephritis?
With long-standing pyelonephritis, invasion of the kidneys by bacteria not only causes damage to the renal tubules, glomeruli, and other structures throughout the kidney.

Consequently, large parts of functional renal tissue are lost, and chronic renal failure can develop.
143. What is nephrotic syndrome?
Nephrotic syndrome is characterized by loss of large quantities of plasma proteins into the urine. In some instances, this occurs without evidence of other major abnormalities of kidney function, but more often it is associated w/some degree of renal failure.
144. What is the cause of the protein loss in the urine in nephrotic syndrome?
The cause is increased permeability of the glomerular membrane.

Therefore, any disease that increase the permeability of this membrane can cause the nephrotic syndrome.
145. What 3 conditions can cause nephrotic syndrome?
1. Chronic glomerulonephritis, which affect primarily the glomeruli and often causes greatly increase permeability of the glomerular membrane.

2. Amyloidosis, which results from deposition of an abnormal proteinoid substance in the walls of the blood vessels and seriously damages the basement membrane of the glomeruli.

3. Minimal change nephrotic syndrome, which is associated w/no major abnormality in the glomerular capillary membrane that can be detected w/light microscopy.
146. What causes the minimal change nephropathy?
Minimal change nephropathy has been found to be associated w/loss of the negative charges that are normally present in the glomerular capillary basement membrane.

This loss of negative charges may have resulted from antibody attack on the membrane. Loss of normal negative charges in the basement membrane of the glomerular capillaries allows proteins, esp albumin, to pass thru the glomerular membrane w/ease b/c the negative charges in the basement membrane normally repel the negatively charged plasma proteins.

Can lead to severe edema.
147. Loss of functional nephrons causes...
Causes the surviving nephrons to excrete more water and solutes.

However, metabolic waste products such as creatinine and urea accumulate in direct proportion to the number of nephrons destroyed.
148. Why do these other substances accumulate when water and electrolytes do not?
Substances such as creatinine and urea depend largely on glomerular filtration for their excretion, and they are not reabsorbed as avidly as the electrolytes.

Creatinine, for example, is not reabsorbed at all, and the excretion rate is equal to the rate at which it is filtered.
149. Equation for creatinine filtration and excretion rate
Creatinine filtration rate =

= GFR x Plasma creatinine concentration

= Creatinine excretion rate
150. What happens when the GFR decreases?
If the GFR decreases, the creatinine excretion rate also transiently decreases, causing accumulation of creatinine in the body fluids and raising plasma concentration until the excretion rate of creatinine returns to normal - the same rate at which creatinine is produced in the body.

Thus, under steady state conditions, the creatinine excretion rate equals the rate of creatinine production, despite reductions in GFR; however, this normal rate of creatinine excretion occurs at the expense of elevated plasma creatinine concentration.
151. Phosphate, urate, and hydrogen ions and GFR
Some solutes, such as phosphate, urate, and hydrogen ions, are often maintained near the normal range until GFR fall below 20-30% of normal.

Thereafter, the plasma concentrations of these substances rise, but not in proportion to the fall in GFR.

Maintenance of relatively constant plasma concentrations of these solutes as GFR declines is accomplished by excreting progressively larger fractions of the amounts of these solutes that are filtered at the glomerular capillaries; this occurs by decreasing the rate of tubular reabsorption or, in some instances, by increasing tubular secretion rates.
152. What about sodium and chloride ions?
Their plasma concentrations are maintained virtually constant even with severe decreases in GFR.

This is accomplished by greatly decreasing tubular reabsorption of these electrolytes.

For example, with a 75% loss of functional nephrons, each surviving nephron must excrete 4x as much Na and 4x as much volume as under normal conditions.
153. What causes this adaptation of the nephrons?
Part of this adaptation occurs b/c of increased blood flow and increased GFR in each of the surviving nephrons, owing to hypertrophy of the blood vessels and glomeruli, as well as functional changes that cause the blood vessels to vasodilate.

Even with large decreases in the total GFR, normal rates of renal excretion can still be maintained by decreasing the rate at which the tubules reabsorb water and solutes.
154. What is isosthenuria?
Isosthenuria is the inability of the kidney to concentrate or dilute the urine.

One important effect of the rapid rate of tubular flow that occurs in the remaining nephrons of diseased kidneys is that the renal tubules lose their ability to concentrate or dilute the urine.
155. Why is the concentrating ability of the kidney impaired in diseased kidneys?

Two reasons...
1. The rapid flow of tubular fluid through the collecting ducts prevents adequate water reabsorption

2. The rapid flow through both the loop of Henle and the collecting ducts prevents the countercurrent mechanism from operating effectively to concentrate the medullary interstitial fluid solutes.

Therefore, as progressively more nephrons are destroyed, the max concentrating ability of the kidney declines, and urine osmolarity and specific gravity approach the osmolarity and specific gravity of the glomerular filtrate.
156. Why is the diluting mechanism in diseased kidneys also impaired?
The diluting mechanism in the kidney is also impaired when the number of nephrons decreases b/c the rapid flushing of fluid through the loops of Henle and the high load of solutes such as urea cause a relatively high solute concentration in the tubular fluid of this part of the nephron.

As a consequence, the diluting capacity of the kidney is impaired, and the minimal urine osmolarity and specific gravity approach those of the glomerular filtrate.
157. Which is more indicative of renal function when a person's water intake is restricted for 12+ hours - diluting or concentrating?
B/c the concentrating mechanisms becomes impaired to a greater extent than does the diluting mechanism in chronic renal failure, an important clinical test of renal function is to determine how well the kidneys can concentrate urine when a person's water intake is restricted for 12 or more hours.
158. The effect of complete renal failure on the body fluids depends on what two things?
1. Water and food intake
2. The degree of impairment of renal function
159. What are the 4 effects of renal failure on the body fluids (AKA uremia)?
1. Generalized edema resultign from water and salt retention
2. Acidosis resulting from failure of the kidneys to rid the body of nromal acidic products
3. High concentration fo the nonprotein nitrogens - especially urea, creatinine, and uric acid- resulting from failure of teh body to excrete the metabolic end products of proteins
4. High concentrations of other substances excreted by the kidney, including phenols, sulfates, phosphates, potassium and guanidine bases.
160. Water retention and development of edema in renal failure
Edema usually does not become severe until kidney function falls to 25% of normal or lower.

Even the small fluid retention that does occur, along with increased secretion of renin and angiotensin II that usually occurs in ischemic kidney diseases, often causes severe hypertension in chronic renal failure.

Thus, dialysis is usually required to preserve life but it usually results in hypertension. In most of these patients, severe reduction of salt intake or removal of ECF by dialysis can control the hypertension.
161. Uremia and azotemia
The nonprotein nitrogens include urea, uric acid, creatinine, and others. These end products must be removed from the body to ensure continued normal protein metabolism in the cells.

The concentrations of these, particularly of urea, can rise to as high as 10x normal during 1-2 weeks of total renal failure. With chronic renal failure, the concentrations rise appox in proportion to the degree of reduction in functional nephrons.

Thus, measures of urea and creatinine provide an important means for assessing the degree of renal failure.
162. What causes acidosis in renal failure?
When the kidneys fail to function, acid accumulates in the body fluids. The buffers of the body can be overwhelmed and the blood pH falls drastically.
163. What causes anemia in those with chronic renal failure?
Patients with severe chronic renal failure almost always develop anemia.

The most important cause of this is decreased renal secretion of erythropoietin, which leads to diminished RBC production.
164. What causes osteomalacia in chronic renal failure?
Serious damage to the kidney greatly reduces the blood concentration of active vitamin D, which in turn decreases intestinal absorption of calcium and the availability of calcium to the bones.

Another cause is the rise in serum phosphate concentration that occurs as a result of decreased GFR, which leads to increased in PTH secretion - thus causing secondary hyperparathyroidism.
165. How do renal lesions cause hypertension?
Renal lesions either decrease GFR -or- increase tubular reabsorption usually lead to hypertension of varying degrees.
166. Three types of renal abnormalities that can cause hypertension
1. Increased renal vascular resistance (renal artery stenosis)
2. Decreased glomerular capillary filtration coefficient (glomerulonephritis)
3. Excessive tubular sodium reabsorption (hyperadosteronism)
167. What are the most likely sequence of events that cause hypertension in patchy renal damage?
1. Ischemic kidney tissue itself excretes less than normal amts of water and salt
2. The renin secreted by the ischemic kidney and subsequent increased angiotensin II formation, affects the nonischemic kidney tissue, causing it to also retain salt and water
3. Excess salt and water cause hypertension in the usual manner.
168. . In what condition does a kidney disease cause loss of entire nephrons and leads to renal failure - but may not cause hypertension?
With minimal salt intake, this condition might not cause clinically significant hypertension, b/c even a slight rise in BP will raise the GFR and decrease tubular sodium reabsorption sufficiently to promote enough water and salt excretion in the urine, even with the few nephrons that remain intact.

However, the patient with this type of abnormality may develop hypertension if salt intake increases.
169. What is renal glycosuria?
Failure of the kidneys to reabsorb glucose.

The blood glucose concentration may be normal, but the transport mechanisms for tubular reabsorption of glucose is greatly limited or absent.

Consequently, large amts of glucose pass into the urine each day. Diabetes is associated with this as well, so renal glycosuria must be ruled out first.
170. What is aminoaciduria? What can it result in?
Failure of the kidneys to reabsorb AAs.

Rarely, a condition called generalized aminoaciduria results from deficient reabsorption of all AAs; more frequently, deficiencies of specific carrier systems may result in:

1. Essential cystinuria, in which large amts of cystine fail to be reabsorbed and often form kidney stones
2. Simple glycinuria, in which glycine fails to be absorbed
3. β-aminoisobutyricaciduria, which occurs in about 5% of all people but has not clinical significance.
171. What is renal hypophosphatemia?
Failure of the kidneys to reabsorb phosphate.

Usually not clinically significant in the short term but over a long period, a low phosphate level can cause diminished calcification of the bones, causing the person to develop vitamin D resistant rickets.
172. What causes renal tubular acidosis?
Failure of the tubules to secrete hydrogen ions. As a result, large amts of sodium bicarb are continually lost in the urine. This causes a continued state of metabolic acidosis.
173. What is nephrogenic diabetes insipidus?
Failure of the kidneys to respond to ADH.

This causes large quantities of dilute urine to be excreted. As long as the person is supplied with plenty of water, the person is OK. However, with dehydration, it can become problematic.
174. What is Fanconi's syndrome?
A generalized reabsorptive defect of the renal tubules.

Fanconi's syndrome is usually associated with increased urinary excretion of virtually all AAs, glucose, and phosphate. It can also cause:
1. failure to reabsorb bicarb, which causes metabolic acidosis
2. increased excretion of potassium and sometimes calcium
3. nephrogrenic diabetes insipidus
175. What are 3 causes of Fanconi's syndrome? What part of the kidneys is especially affected in Fanconi's syndrome?
1. Hereditary defects in cells transport mechanisms
2. Toxins or drugs that injure the renal tubular epithelial cells
3. Injury to the renal tubular cells as a result of ischemia

The proximal tubular cells are especially affected in Fanconi's syndrome caused by tubular injury, b/c these cells reabsorb and secrete many of the drugs and toxins that can cause damage.
176. The rate of movement of solute across the dialyzing membrane depends on what four things?
1. Concentration gradient of the solute between the two solutions
2. Permeability of the membrane to the solute
3. Surface area of the membrane
4. Length of time that the blood and fluid remain in contact w/the membrane