Unit V (25-32) - The body fluids and kidneys Flashcards
The major force favoring filtration across the glomerular capillary wall is the:
a. Oncotic pressure of the plasma.
b. Oncotic pressure of the glomerular filtrate.
c. Hydrostatic pressure of the blood.
d. Hydrostatic pressure of the glomerular filtrate.
e. Ultrafiltration coefficient
C. Hydrostatic pressure of the blood.
Cunningham Ch 41
The glomerular filtration rate (GFR) is the:
a. Volume of blood filtered by the kidneys per minute per
kilogram of body weight.
b. Volume of plasma filtered by the kidneys per minute per kilogram of body weight.
c. Volume of urine produced by the kidneys per minute per kilogram of body weight.
d. Volume of glomerular filtrate formed by the kidneys per minute per kilogram of body weight.
e. Volume of blood cleared of creatinine by the kidneys per minute per kilogram of body weight.
d. Volume of glomerular filtrate formed by the kidneys per minute per kilogram of body weight.
Cunningham Ch 41
In clinical practice the GFR is often estimated by determining the rate of creatinine clearance. The rate of creatinine clearance is the:
a. Volume of plasma cleared of creatinine/min/kg
b. Volume of glomerular filtrate formed/min/kg
c. Weight of creatinine filtered from the blood/min/kg
d. Weight of creatinine per volume of urine formed/min/kg
e. Difference between the rate of plasma flow in the afferent and efferent arterioles.
A. Volume of plasma cleared of creatinine/min/kg
Cunningham Ch 41
The two major characteristics that determine whether a blood component is filtered or retained in the capillary lumen are its:
a. Molecular radius and molecular weight.
b. Molecular radius and lipid solubility.
c. Molecular radius and plasma concentration.
d. Molecular radius and electrical charge.
e. Molecular weight and length.
D. molecular radius and electrical charge
Cunningham Ch 41
The GFR is increased by:
a. A low-protein meal.
b. Afferent arteriolar constriction.
c. Tubuloglomerular feedback.
d. Release of atrial natriuretic peptide.
e. Activation of RAAS
E. Activation of RAAS
Cunningham Ch 41
Which segment of the renal tubule is responsible for the reabsorption of the bulk of filtered solutes?
a. Proximal tubule
b. Thin limbs of Henle’s loop
c. Thick ascending limb of Henle’s loop
d. Distal convoluted tubule
e. Collecting duct
A. Proximal tubule
Cunningham Ch 42
The main driving force for the reabsorption of solutes from the tubule fluid is:
a. Active transport of solutes across the apical plasma
membrane.
b. Secondary active transport of solutes across the apical
plasma membrane.
c. Active transport of Na+ from the tubule epithelial cell
across the basolateral plasma membrane by the electrogenic Na+ channel.
d. Active transport of Na+ from the tubule epithelial cell
across the basolateral plasma membrane by the Na+,K+-
ATPase pump.
e. Passive diffusion of solutes through the paracellular
pathway.
D. Active transport of Na+ from the tubule epithelial cell
across the basolateral plasma membrane by the Na+,K+-
ATPase pump.
Cunningham Ch 42
Glucose is found in the urine of an animal when:
a. Glucose transporters in the proximal tubule are inhibited by furosemide.
b. Glucose secretion in the proximal tubule is stimulated by angiotensin II.
c. Glomerular filtration barrier is defective causing increased glucose in the tubule fluid.
d. Plasma glucose is elevated, increasing glucose concentration in the tubule fluid above the proximal tubule transport capacity.
e. Elevated plasma glucose stimulates proximal tubule glucose secretion.
D. Plasma glucose is elevated, increasing glucose concentration in the tubule fluid above the proximal tubule transport capacity.
Cunningham Ch 42
The ultimate rate of excretion of K+ in the urine is determined by the:
a. Concentration of K+ in the glomerular filtrate.
b. Proximal tubule, which reabsorbs or secretes K+ to meet the physiological requirements of the animals.
c. Thick ascending limb, where K+ secretion is enhanced by high plasma K+ concentrations.
d. Distal convoluted tubule, which has K+ pumps that are
inserted in the apical or basolateral plasma membranes,
depending on the need for reabsorption or secretion of K+.
e. Collecting duct, where the principal cells are capable of K+ secretion, and the intercalated cells are capable of K+ reabsorption.
E. Collecting duct, where the principal cells are capable of
K+ secretion, and the intercalated cells are capable of K+
reabsorption.
Cunningham Ch 42
Which of the following two are effects of aldosterone on Na+ transport in the connecting segment and collecting duct?
a. Enhances the permeability of Na+ channels in the apical plasma membrane, thereby enhancing Na+ reabsorption
b. Stimulates Na+,K+-ATPase activity in the basolateral plasma membrane, thereby enhancing Na+ reabsorption
c. Reduces the Na+ permeability of the apical plasma membrane, thereby inhibiting Na+ reabsorption
d. Reduces Na+,K+-ATPase activity in the basolateral plasma membrane, thereby inhibiting Na+ reabsorption
e. Reduces the K+ permeability of the apical plasma membrane, thereby inhibiting K+ reabsorption
A. Enhances the permeability of Na+ channels in the apical
plasma membrane, thereby enhancing Na+ reabsorption
and
B. Stimulates Na+,K+-ATPase activity in the basolateral plasma membrane, thereby enhancing Na+ reabsorption
Cunningham Ch 42
The bulk of filtered water is reabsorbed by which renal tubule segment?
a. Proximal tubule
b. Thin limbs of Henle’s loop
c. Thick ascending limb of Henle’s loop
d. Cortical collecting duct
e. Inner medullary collecting duct
A. Proximal tubule
Cunningham Ch 43
The kidney responds rapidly to changing water requirements. The ability to alter quickly the rate of water excretion by greatly concentrating or diluting the urine is the result of several factors. Which of the following does not contribute to this ability?
a. Generation of hypertonic medullary interstitium
b. Countercurrent flow and differential salt and water permeabilities in the thin limbs of Henle’s loop
c. Dilution of the tubule fluid by the thick ascending limb and the distal convoluted tubule
d. Responsiveness of the collecting duct to antidiuretic
hormone (ADH)
e. ADH-regulated countercurrent flow and enhanced water permeability in the vasa recta
E. ADH-regulated countercurrent flow and enhanced water
permeability in the vasa recta
Cunningham Ch 43
The hypertonic medullary interstitium is generated in large part by:
a. Active transport of Na+ by the straight portion of the proximal tubule.
b. Active reabsorption of Na+ by the water-impermeable,
ascending thin limb of Henle’s loop.
c. Active reabsorption of Na+ by the water-impermeable,
thick ascending limb of Henle’s loop.
d. Increase in water channels in the apical plasma membrane of collecting duct cells under the influence of
vasopressin.
e. Enhanced urea permeability of the thick ascending limb of Henle’s loop under the influence of vasopressin.
C. Active reabsorption of Na+ by the water-impermeable,
thick ascending limb of Henle’s loop.
Cunningham Ch 43
In dehydration, ADH is released, which reduces water excretion by:
a. Enhancing water reabsorption in the proximal tubules by stimulating Na+,K+-ATPase.
b. Enhancing water reabsorption in the thick ascending limb by stimulating the insertion of aquaporin-2 water channels into the apical plasma membrane.
c. Enhancing water reabsorption in the collecting duct by
stimulating Na+,K+-ATPase activity.
d. Enhancing water permeability in the collecting duct by
stimulating the insertion of aquaporin-2 water channels
into the apical plasma membrane.
e. Reducing the glomerular filtration rate by activation of
tubuloglomerular feedback.
D. Enhancing water permeability in the collecting duct by
stimulating the insertion of aquaporin-2 water channels
into the apical plasma membrane.
Cunningham Ch 43
In carnivores, the usual role of the kidney in maintaining acid base homeostasis is to:
a. Secrete excess bicarbonate.
b. Secrete excess ammonia.
c. Secrete excess acid.
d. Secrete excess carbon dioxide.
e. Secrete excess phosphate buffer.
C. Secrete excess acid
Cunningham Ch. 44
The bulk of acid secretion (bicarbonate reabsorption) is
accomplished by which renal tubule segment?
a. Proximal tubule
b. Thin limbs of Henle’s loop
c. Thick ascending limb of Henle’s loop
d. Distal convoluted tubule
e. Collecting duct
A. Proximal tubule
Cunningham Ch. 44
Which of the following factors does NOT contribute to efficient acid excretion (bicarbonate reabsorption) by the renal tubules?
a. Primary active transport of bicarbonate
b. Intraluminal buffering by bicarbonate
c. Intraluminal buffering by ammonia and phosphate
d. Intracellular and membrane-associated carbonic anhydrase
e. Transmembrane proton transport by the Na+/H+ exchanger, H+-ATPase pump, and H+,K+-ATPase pump
A. Primary active transport of bicarbonate
Cunningham Ch. 44
Which of the following statements regarding mechanisms of acid-base regulation by the collecting duct is FALSE?
a. The cortical collecting duct responds to acidosis by increasing the net rate of acid secretion.
b. The cortical collecting duct responds to alkalosis with net bicarbonate secretion.
c. Proton and bicarbonate transport in the collecting duct are only slightly altered in response to systemic acid-base disturbances.
d. The collecting duct determines the ultimate pH of the
urine.
e. The intercalated cells are largely responsible for acid secretion by the collecting duct.
C.
Proton and bicarbonate transport in the collecting duct are only slightly altered in response to systemic acid-base
disturbances.
Cunningham Ch. 44
What is the role of renal ammonia metabolism in the renal response to acidosis, at least in dogs and rodents?
a. Acidosis increases ammoniagenesis in the proximal tubule, which increases the generation of new bicarbonate ions.
b. Acidosis increases collecting duct ammonia secretion,
which enhances acid secretion.
c. Acidosis stimulates ammoniagenesis in the proximal tubule and inhibits collecting duct ammonia secretion, which increases ammonia buffering of the plasma.
d. Renal ammonia metabolism does not contribute to renal acid-base regulation.
e. Both a and b.
A. Acidosis increases ammoniagenesis in the proximal tubule, which increases the generation of new bicarbonate ions.
&
B. Acidosis increases collecting duct ammonia secretion,
which enhances acid secretion.
Cunningham Ch. 44
What proportion of body weight is ECF vs ICF?
ECF - 1/3
ICF - 2/3
What is the proportion of interstitial fluid vs plasma? and what is the main difference between the two?
Interstitial - 75% - more negative
Plasma - 25% - more negative (bc of the proteins), also has more cations
What is normal osmolarity in dogs and cats?
Dogs - 280-300
Cats - 280 - 330
Factors that lead to edema formation
- Increased capillary filtration
a. increase capillary permeability (filtration coefficient)
b. increased capillary hydrostatic pressure
c. decreased plasma oncotic pressure (low protein) - Lymphatic obstruction
How is the hydrostatic pressure different in the glomerular capillaries compared to the peritublar capillaries? why?
glomerular - higher (60mmHg) - rapid filtration
peritubular - lower (13mmHg)- rapid reabsorption
Which of the following nerves provides motor innervation to the detrusor muscle? A. Pelvic n. B. Pudendal n. C. Femoral n. D. Hypogastric n.
A. Pelvic n.
Parasympathetic nerve - arises from S2-S3 and provides the principal nerve supply to the bladder. Also provides sensory to the bladder by detecting degree of stretch.
Which of the following nerves provides sympathetic innervation to the bladder? A. Pelvic n. B. Pudendal n. C. Femoral n. D. Hypogastric n.
D. Hypogastric n.
Responsible for bladder vasculature +/- pain sensation
What is the lowest mean arterial pressure at which the kidney is able to maintain relatively constant GFR and renal blood flow? A. 40mmHg B. 60mmHg C. 70 mmHg D. 90 mmHg
B. 60mm Hg
In normal kidneys, which of the following is true of the osmolarity of renal tubular fluid that flows through the early distal tubule in the region of the macula densa?
a. Usually isotonic compared with plasma
b. Usually hypotonic compared with plasma
c. Usually hypertonic compared with plasma
d. Hypertonic, compared with plasma, in antidiuresis
B Usually hypotonic compared with plasma
As water flows up the ascending limb of the loop of Henle, solutes are reabsorbed, but this segment is relatively imipermeable to water; progressive dilution of the tubular fluid occurs so that the osmolarity decreases to approximately 100 mOsm/L by the time the fluid reaches the early distal tubule. Even during maximal antidiruesis, this portion of the renal tubule is relatively impermeable to water and is therefore called the diluting segment of the renal tubule.
Guyton 13 ed. P 378-379
When dietary intake of K+ increases, body K+ balance is maintained by an increase in K+ excretion primarily by which of the following?
a. Decreased glomerular filtration of K+
b. Decreased reabsorption of K+ by the proximal tubule
c. Decreased reabsorption of K+ by the thick ascending limb of the loop of Henle
d. Increased K+ secretion by the late distal and collecting tubules
e. Shift of K+ into the intracellular compartment
D Increased K+ secretion by the late distal and collecting tubules
Most of the daily variation in K+ excretion is caused by changes in K+ secretion in the late distal tubules and collecting tubules. Therefore, when the dietary intake of K+ increases, the total body balance of K+ is maintained primarily by an increase in K+ secretion in these tubular segments. Increased K+ intake has little effect on GFR or on reabsorption of K+ in the proximal tubule and loop of Henle. Although high K+ intake may cause a slight shift of K+ into the intracellular compartment, a balance between intake and output must be achieved by increasing the excretion of K+ during high K+ intake.
Guyton 13 ed.
Which tends to increase GFR?
a. Increased afferent arteriolar resistance
b. Decreased efferent arteriolar resistance
c. Increased glomerular capillary filtration coefficient
d. Increased Bowman’s capsule hydrostatic pressure
e. Decreased glomerular capillary hydrostatic pressure
C Increased glomerular capillary filtration coefficient
This is the product of the hydraulic conductivity and surface area of the glomerular capillaries.
Guyton 13ed. P 337-340
The GFR of a patient with glomerulonephritis decreases by 50% and remains at that level. For which substance would you expect to find the greatest increase in plasma concentration?
a. Creatinine
b. K+
c. Glucose
d. Na+
e. Phosphate
f. H+
A Creatinine
A 50% reduction of GRF would approximately double the plasma creatinine concentration because creatinine is not reabsorbed or secreted and its excretion depends largely on glomerular filtration. Therefore, when GFR decreases, the plasma concentration of creatinine increases until the renal excretion of creatinine returns to normal. Plasma concentrations of glucose, K+, Na+, and H+ ions are closely regulated by multiple mechanisms that keep them relatively constant even when GFR falls to very low levels. Plasma phosphate concentration is also maintained near normal until GFR falls to below 20-30% of normal.
Guyton 13 ed. P 435-436
The maximum clearance rate possible for a substance that is totally cleared from the plasma is equal to which of the following?
a. GFR
b. Filtered load of that substance
c. Urinary excretion rate of that substance
d. Renal plasma flow
e. Filtration fraction
D Renal plasma flow
If a substance were completely cleared from the plasma, the clearance rate of that substance would equal the total renal plasma flow. In other words, the total amount of substance delivered to the kidneys in the blood (renal plasma flow x concentration of substance in the blood) would equal the amount of that substance excreted in the urine. Complete renal clearance of a substance would require both glomerular filtration and tubular secretion of that substance.
Guyton 13 ed. P 365-368
Which changes would you expect to find after administering a vasodilator drug that caused a 50% decrease in afferent arteriolar resistance and no change in arterial pressure?
a. Decreased renal blood flow, decreased GFR, and decreased peritubular capillary hydrostatic pressure
b. Decreased renal blood flow, decreased GFR, and increased peritubular capillary hydrostatic pressure
c. Increased renal blood flow, increased GFR, and increased peritubular capillary hydrostatic pressure
d. Increased renal blood flow, increased GFR, and no change in peritubular capillary hydrostatic pressure
e. Increased renal blood flow, increased GFR, and decreased peritubular capillary hydrostatic pressure
C Increased renal blood flow, increased GFR, and increased peritubular capillary hydrostatic pressure
A 50% reduction in afferent arteriolar resistance with no change in arterial pressure would increase renal blood flow and glomerular hydrostatic pressure, thereby increasing GFR. At the same time, the reduction in afferent arteriolar resistance would raise peritubular capillary hydrostatic pressure.
Guyton 13 ed. P 338-340
Which change tends to increase peritubular capillary fluid reabsorption?
a. Increased blood pressure
b. Decreased filtration fraction
c. Increased efferent arteriolar resistance
d. Decreased angiotensin II
e. Increased renal blood flow
C Increased efferent arteriolar resistance
The balance of hydrostatic and colloid osmotic forces in the peritubular capillaries determines peritubular capillary fluid reabsorption. Increased efferent arteriolar resistance reduces peritubular capillary hydrostatic pressure and therefore increases the net force favoring fluid reabsorption. Increased blood pressure tends to raise peritubular capillary hydrostatic pressure and reduce fluid reabsorption. Decreased filtration fraction increases the peritubular capillary colloid osmotic pressure and tends to reduce peritubular capillary reabsorption. Decreased angiotensin II causes vasodilation of efferent arterioles, raising peritubular capillary hydrostatic pressure, decreasing reabsorption, and decreasing tubular transport of water and electrolytes. Increased renal blood flow also tends to raise peritubular capillary hydrostatic pressure and decrease fluid reabsorption.
Guyton 13 ed. P 360-362
An adrenal tumor that causes excess aldosterone secretion would tend to ____ plasma K+ concentration, ____ plasma pH, ____ renin secretion, and ____ blood pressure.
a. Decrease, decrease, decrease, decrease
b. Decrease, increase, decrease, increase
c. Decrease, decrease, decease, increase
d. Decrease, increase, increase, increase
e. Increase, increase, decrease, increase
f. Increase, decrease, decrease, increase
B Decrease, increase, decrease, increase
Excess aldosterone increases sodium reabsorption and potassium secretion by the principal cells of the collecting tubules, causing sodium retention, increased blood pressure, and decreased renin secretion while increasing excretion of potassium and tending to decrease plasma potassium concentration. Excess aldosterone also causes a shift of potassium from the extracellular fluid into the cells, further reducing plasma potassium concentration. Aldosterone excess also stimulates hydrogen ion secretion and bicarbonate reabsorption by the intercalated cells and tends to increase plasma pH (alkalosis). Therefore the classic manifestations of excess aldosterone secretion are hypokalemia, hypertension, alkalosis, and low renin levels.
Guyton 13 ed. P 356-357, 390
Which of the following tends to increase potassium secretion by the cortical collecting tubule?
a. A diuretic that inhibits the action of aldosterone (e.g. spironolactone)
b. A diuretic that decreases loop of Henle sodium reabsorption (e.g. furosemide)
c. Decreased plasma potassium concentration
d. Acute metabolic acidosis
e. Low sodium intake
B A diuretic that decreases loop of Henle sodium reabsorption (e.g. furosemide)
Potassium secretion by the cortical collecting ducts is stimulated by 1) aldosterone, 2) increased plasma potassium concentration, 3) increased flow rate in the cortical collecting tubules, and 4) alkalosis. Therefore a diuretic that inhibits aldosterone, decreased plasma potassium concentration, acute acidosis, and low sodium intake would all decrease potassium secretion by the cortical collecting tubules. A diuretic that decreases loop of Henle sodium reabsorption, however, would tend to increase the flow rate in the cortical collecting tubule and therefore stimulate potassium secretion.
Guyton 13 ed. P 392, 396
Which diuretic inhibits Na-2Cl-K co-transport in the loop of Henle as its primary action? A. Thiazide diuretic B. Furosemide C. Carbonic anhydrase inhibitor D. Osmotic diuretic E. Amiloride F. Spironolactone
B. Furosemide
Furosemide is a powerful inhibitor of the Na-2Cl-K co-transporter in the LOH. Thiazide diuretics primarily inhibit NaCl reabsorption into the distal tubule, whereas carbonic anhydrase inhibitors decrease bicarbonate reabsorption in the tubules. Amiloride inhibits sodium channel activity, whereas spironolactone inhibits the action of mineralocoricoids in the renal tubules. Osmotic diuretics inhibit water and solute reabsorption by increasing osmolarity of the tubular fluid.
Guyton 13 ed. p 428
A selective decrease in efferent arteriolar resistance would \_\_\_\_ glomerular hydrostatic pressure, \_\_\_\_ GFR, and \_\_\_\_ renal blood flow. A. Increase, increase, increase B. Increase, decrease, increase C. Increase, decrease, decrease D. Decrease, increase, decrease E. Decrease, decrease, increase F. Decrease, increase, increase
E. Decrease, decrease, increase
Decreased efferent arteriolar resistance would increase renal blood flow while reducing glomerular hydrostatic pressure, which, in turn, would tend to decrease the GFR.
Guyton 13 ed. P 338-339
Which nephron segment is the primary site of magnesium reabsorption under normal conditions? A. Proximal tubule B. Decsending limb of the loop of Henle C. Ascending limb of the loop of Henle D. Distal convoluted tubule E. Collecting ducts
C. Ascending limb of the loop of Henle
About 65% of the filtered load of Mg is reabsorbed here. The proximal tubule normally reabsorbes only about 25% of filtered Mg., and the distal and collecting tubules reabsorb less than 5%
Guyton 13 ed. P 398
The principal cells in the cortical collecting tubules
A. are the main site of action of the thiazide diurectics
B. have Na-Cl-K co-transporters
C. are highly permeable to urea during antidiuresis
D. are an important site of action of amiloride
E. are the main site of action of furosemide
D. are an important site of action of amiloride
Amiloride blocks entry of sodium into sodium channels. Thiazide diuretics inhibit Na-Cl co-transport in the early distal tubule. The collecting tubule cells are not very permeable to urea. Furosemide inhibits the Na-Cl-K co-transporter in the thick ascending LOH.
The type A intercalated cells in the collecting tubules
A. are highly permeable to urea during antidiuresis
B. secrete K
C. secrete H
D. are the main site of action of furosemide
E. are the main site of action of thiazide diuretics
C. secrete H
Type A intercalated cells of the collecting tubules are important sites for H secretion and K reabsorption, but the collecting tubules are not highly permeable to urea. Furosemide acts mainly in the thick ascending LOH, and thiazide diuretics act mainly in the early distal tubule.
Guyton 13 ed. p 356-357
Which of the following would be the most likely cause of hypernatremia associated with a small volume of highly concentrate urine (osmolarity = 1400 mOsm/L) in a patient with normal kidneys?
A. Primary aldosteronism
B. Diabetes mellitus
C. Diabetes insipidus
D. Dehydration due to insufficient water intake and heavy exercise.
D. Dehydration due to insufficient water intake and heavy exercise.
This would cause increase plasma sodium concentration, which would then stimulate release of ADH. This would increase water reabsorption in the distal and collecting tubules/ducts, causing a small volume of highly concentrated urine. Primary aldosteronism would be associated with sodium and water retention but normal renal excretion (equal to intake) of sodium and water after a few days. Uncontrolled diabetes mellitus is typically associated with large volumes of urine due to the osmotic diuresis associated with hyperglycemia. Diabetes insipidus is associated with large volumes of dilute urine.
Guyton 13 ed. p 439-440
Which of the following has similar values for both intracellular and interstitial body fluids? A. K ion concentration B. Colloid osmotic pressure C. Na ion concentration D. Cl ion concentration E. Total osmolarity
E. Total osmolarity
Intracellular and extracellular body fluids have the same total osmolarity under steady-state conditions because the cell membrane is highly permeable to water. Therefore, water flows rapidly across the cell membrane until osmotic equilibrium is achieved. The colloid osmotic pressure is determined by the protein concentration, which is considerably higher inside the cell. The cell membrane is also relatively impermeable to K, Na, and Cl, and active transport mechs maintain low intracellular concentrations of sodium and chloride and a high intracellular concentration of potassium.
Guyton 13 ed. p 310-312
Which of the following is true of the tubular fluid that passes through the lumen of the early distal tubule in the region of the macula densa?
A. It is usually isotonic.
B. It is usually hypotonic.
C. It is usually hyertonic.
D. It is hypertonic in antidiuresis.
E. It is hypertonic when the filtration rate of its own nephron decreases to 50% below normal.
B. It is usually hypotonic.
Fluid entering the early distal tubule is almost always hypotonic because sodium and other ions are actively transported out of the thick ascending LOH, whereas this portion of the nephron is virtually impermeable to water. For this reason, the thick ascending limb of the LOH and the early part of the distal tubule are often called the diluting segement.
Guyton 13 ed. p 354-355
Which change tends to increase urinary calcium excretion?
A. Extracellular fluid volume expansion
B. Increased plasma parathyroid hormone concentration
C. Decreased blood pressure
D. Increased plasma phosphate concentration
E. Metabolic alkalosis
A. Extracellular fluid volume expansion
In the proximal tubule, Ca reabsorption usually parallels sodium and water reabsorption. With extracellular volume expansion or increased blood pressure, proximal sodium and water reabsorption is reduced, and a reduction in calcium reabsorption also occurs, causing increased urinary excretion of calcium. Increased parathyroid hormone, increased plasma phosphate concentration, and metabolic alkalosis all tend to decrease the renal excretion of calcium.
Guyton 13 ed. p 396-398
What would tend to decrease GFR by more than 10% in a normal kidney?
A. Decrease in renal arterial pressure from 100 to 85 mm Hg
B. 50% decrease in afferent arteriolar resistance
C. 50% decrease in efferent arteriolar resistance
D 50% increase in the glomerular capillary filtration coefficient
E. Decrease in plasma colloid osmotic pressure from 28 to 20 mm Hg
C. 50% decrease in efferent arteriolar resistance
This would cause a large decrease in GFR - greater than 10%. A decrease in renal artery pressure from 100 to 85 mm Hg would cause only a slight decrease in GFR in a normal, autoregulating kidney. A decrease in afferent arteriole resistance, a decrease in plasma colloid osmotic pressure, or an increase in the glomerular capillary filtration coefficient would all tend to increase GFR.
Guyton 13 ed. p 337-340, 343
Which statement is true?
A. ADH increases water reabsorption from the ascending LOH
B. Water reabsorption from the descending LOH is normally less than that from the ascending LOH
C. Na reabsorption from the ascending LOH is normally less than that from the descending LOH
D. Osmolarity of fluid in the early distal tubule would be less than 300 mOsm/L in a dehydrated patient with normal kidneys and increased ADH levels
E. ADH decreases the urea permeability in the medullary collecting tubules.
D. Osmolarity of fluid in the early distal tubule would be less than 300 mOsm/L in a dehydrated patient with normal kidneys and increased ADH levels
This is because the ascending limb of LOH and the early distal tubule are relatively impermeable to water, even in the presence of ADH. Therefore, the tubular fluid becomes progressively more dilute in these segments compared with plasma. ADH does not influence water reabsorption in the ascending limb of the LOH. The ascending limb, however, reabsorbs Na to a much greater extent than does the descending limb. Another important action of ADH is to increase the urea permeability in the medullary collecting ducts, which contributes to the hyperosmotic renal medullary interstitium in antidiuresis.
Guyton 13 ed. p 378-379
Which would tend to increase Ca reabsorption in the renal tubule?
A. Extracellular fluid volume expansion
B. Increased plasma parathyroid hormone concentration
C. Increased blood pressure
D. Decreased plasma phosphate concentration
E. Metabolic acidosis
B. Increased plasma parathyroid hormone concentration
This would occur in the thick ascneding LOH and distal tubules. All others are associated with decreased Ca reabsoprtion by the renal tubules.
Guyton 13 ed. p 396-397
At which renal tubular sites would the concentration of creatinine be expected to be highest in a normally hydrated person? A. Same in all segments B. Glomerular filtrate C. End of the proximal tubule D. End of the LOH E. Distal tubule F. Collecting duct
F. Collecting duct
This is because creatinine concentraion is progressively increased as water is reabsorbed along the renal tubular segments.
Guyton 13 ed. p 359
Increases in both renal blood flow and GFR are caused by which mech?
A. Dilation of the afferent arterioles
B. Increased glomerular capillary filtration coefficient
C. Increased plasma colloid osmotic pressure
D. Dilation of the efferent arterioles
A. Dilation of the afferent arterioles
This lead to an increase in glomerular hydrostatic pressure and therefore an increase in GFR, as well as an increase in renal blood flow. Increased glomerular capillary filtration coefficient would also raise the GFR but would not be expected to alter renal blood flow. Increased plasma colloid osmotic pressure or dilation of the efferent arterioles would both tend to reduce GFR. Increased blood viscosity would tend to reduce blood flow and GFR.
Guyton 13 ed. P 337-341
With a decrease in proteins (hypoproteinemia), anion gap may be
A. Increased
B. Decreased
B. Decreased
Aldosterone site of action is
A. Collecting tubule and duct
B. Proximal tubule, thick ascending LOH/distal tubule, collecting tubule
C. Distal tubule/Collecting tubule and duct
D. Proximal tubule, thick ascending LOH/distal tubule
A. Collecting tubule and duct
Guyton 13 ed. p 362 Table 28-3
Angiotensin II site of action is
A. Collecting tubule and duct
B. Proximal tubule, thick ascending LOH/distal tubule, collecting tubule
C. Distal tubule/Collecting tubule and duct
D. Proximal tubule, thick ascending LOH/distal tubule
B. Proximal tubule, thick ascending LOH/distal tubule, collecting tubule
Guyton 13 ed. p 362 Table 28-3
Antidiuretic hormone site of action is
A. Collecting tubule and duct
B. Proximal tubule, thick ascending LOH/distal tubule, collecting tubule
C. Distal tubule/Collecting tubule and duct
D. Proximal tubule, thick ascending LOH/distal tubule
C. Distal tubule/Collecting tubule and duct
Guyton 13 ed. p 362 Table 28-3
Atrial natriuretic peptide site of action is
A. Collecting tubule and duct
B. Proximal tubule, thick ascending LOH/distal tubule, collecting tubule
C. Distal tubule/Collecting tubule and duct
D. Proximal tubule, thick ascending LOH/distal tubule
C. Distal tubule/Collecting tubule and duct
Guyton 13 ed. p 362 Table 28-3
Parathyroid hormone site of action is
A. Collecting tubule and duct
B. Proximal tubule, thick ascending LOH/distal tubule, collecting tubule
C. Distal tubule/Collecting tubule and duct
D. Proximal tubule, thick ascending LOH/distal tubule
D. Proximal tubule, thick ascending LOH/distal tubule
Guyton 13 ed. p 362 Table 28-3
Which of the following lists ALL effects of aldosterone?
A. inc NaCl, H2O reabsorption, inc K secretion, inc H secretion
B. inc NaCl, H2O reabsorption, inc H secretion
C. inc H2O reabsorption
D. dec NaCl reabsorption
E. dec PO4 reabsorption, inc Ca reabsorption
A. inc NaCl, H2O reabsorption, inc K secretion, inc H secretion
Guyton 13 ed. p 362 Table 28-3
Which of the following lists ALL effects of angiotensin II?
A. inc NaCl, H2O reabsorption, inc K secretion, inc H secretion
B. inc NaCl, H2O reabsorption, inc H secretion
C. inc H2O reabsorption
D. dec NaCl reabsorption
E. dec PO4 reabsorption, inc Ca reabsorption
B. inc NaCl, H2O reabsorption, inc H secretion
Guyton 13 ed. p 362 Table 28-3
Which of the following lists ALL effects of antidiuretic hormone?
A. inc NaCl, H2O reabsorption, inc K secretion, inc H secretion
B. inc NaCl, H2O reabsorption, inc H secretion
C. inc H2O reabsorption
D. dec NaCl reabsorption
E. dec PO4 reabsorption, inc Ca reabsorption
C. inc H2O reabsorption
Guyton 13 ed. p 362 Table 28-3
Which of the following lists ALL effects of atrial natriuretic peptide?
A. inc NaCl, H2O reabsorption, inc K secretion, inc H secretion
B. inc NaCl, H2O reabsorption, inc H secretion
C. inc H2O reabsorption
D. dec NaCl reabsorption
E. dec PO4 reabsorption, inc Ca reabsorption
D. dec NaCl reabsorption
Guyton 13 ed. p 362 Table 28-3
Which of the following lists ALL effects of parathyroid hormone?
A. inc NaCl, H2O reabsorption, inc K secretion, inc H secretion
B. inc NaCl, H2O reabsorption, inc H secretion
C. inc H2O reabsorption
D. dec NaCl reabsorption
E. dec PO4 reabsorption, inc Ca reabsorption
E. dec PO4 reabsorption, inc Ca reabsorption
Guyton 13 ed. p 362 Table 28-3
What are the two main functions of the macula densa?
1) It decreases resistance to blood flow in the afferent arterioles, which raises glomerular hydrostatic pressure and helps return GFR toward normal
2) It increases renin release from the juxtaglomerular cells of the afferent and efferent arterioles, which are the major storage sites for renin.
The macula densa cells sense changes in volume delivery to the distal tubule by way of signals that are not completely understood.
Guyton 13 ed. p 343-344
Where is the macula densa located?
initial portion of the distal tubule in close proximity to the afferent and efferent arterioles
Guyton 13 ed. p 343-344
Where is the juxtaglomerular cells located?
in the walls of the afferent and efferent arterioles.
Guyton 13 ed. p 343-344
How is water added to the body?
Ingestion
Oxidation of CHO
What % of bodyweight is water?
60%
What % of bodyweight is intracellular fluid?
40%
What % of bodyweight is extracellular fluid?
20%
How do plasma and interstitial fluid differ?
Higher protein in plasma
Higher cations in plasma (Donnan effect)
Higher anions in interstitial fluid
Ddx hyponatraemia
Dehydration - adrenal insufficiency, diuretic overuse, v/d
Overhydration - ADH excess, bronchogenic tumours
Ddx hypernatraemia
Dehydration - DI
Overhydration - HAC, hyperaldosteronism
What are the causes of intracellular oedema?
Hyponatraemia
Depression of metabolic systems
Lack of cellular nutrition
Which part of the LOH is the ‘thin’ segment?
Descending and lower end of ascending
Where is the macula densa located?
At the end of the thick, ascending LOH
What are cortical and juxtaglomerular nephrons? How are they different?
Cortical nephron - glomeruli in outer cortex, short LOH than penetrate a short distance into medulla
Juxtaglomerular nephron - glomeruli deeper in cortex, long LOH
JG nephrons have vasa recta
Describe the neuroanatomy of the bladder
Supplied by pelvic nerves via the sacral plexus (S2-3)
Contains sensory + motor fibres
Motor n - parasympathetic fibres
Pudendal nerve - external sphincter (skeletal)
Hypogastric nerves - sympathetic - blood vessels
What innervates the a)detrusor, b)internal sphincter, c)external sphincter
a)pelvic n
b)pelvic n
c)pudendal n
What is the structure of the glomerular capillary membrane?
1 - endothelium
2 - basement membrane
3 - epithelial cells (podocytes)
How does efferent arteriolar constriction affect GFR?
Biphasic
Mild/moderate - slight increase in GFR
Severe - reduces GFR
How does afferent arteriolar constriction affect GFR?
Reduces
What is anatomy of the juxtaglomerular complex?
Macula densa cells in proximal distal tubule
Juxtaglomerular cells in afferent/efferent arteriole
Describe tubuloglomerular feedback
Reduced GRF => slow flow in LOH => increased Na/Cl reabsorption => reduced Na/Cl at macula densa => afferent arteriolar dilation + ^ renin release => efferent arteriolar constriction
What substances are found in higher quantities in plasma than glomerular filtrate?
Albumin
Calcium
Fatty acids
Describe the structure of the glomerular capillary membrane and how they alter filtration
Endothelium (with fenestrate). Endothelial proteins negatively charged - repeals plasma proteins
Basement membrane - mesh of collagen and proteoglycans. PGs negatively charged
Podocytes (with slit pores) - epithelium negatively charged
What conditions are associated with a reduction in glomerular capillary filtration coefficient?
CKD (reduced number of glomerular capillaries)
Systemic hypertension
How if filtration fraction calculated?
FF = GFR/RBF
What factors influence the glomerular capillary colloid osmotic pressure?
Arterial plasma osmotic pressure
Filtration fraction (affected by GFR and RBF)
How does efferent arteriolar constriction affect GFR?
Biphasic
If mild/moderate, slight increase
If severe, decreases (due to increased FF and glomerular colloid oncotic pressure)
How is renal blood flow regulated?
Tubuloglomerular feedback
Myogenic autoregulation
How do dietary protein and hyperglycaemia affect renal blood flow and GFR?
Increase both
Amino acids/glucose reabsorbed with sodium => reduced sodium delivery to macula densa => afferent arteriolar dilation
What are the main primary active transport pumps in the renal tubules?
Na-K ATPase
H+ ATPase
H-K ATPase
Ca ATPase
Describe the renal tubular Na-K ATPase pump
Na exchanged for K at basolateral membrane using ATPase
Na+ passively diffuses across luminal membrane along concentration and electrical gradient
How is the proximal tubule adapted for Na reabsorption?
Brush border - ^ surface area
Carrier proteins for facilitated diffusion
^Mitochondria
Intercellular + basal channels
Describe glucose reabsorption in the proximal tubule
Na-K ATPase in basolateral membrane creates Na concentration gradient
SGLT 1 and 2 in brush border absorb glucose up concentration gradient
Glucose diffuses out of cell using glucose transporters GLUT1 and GLUT2
What are the sodium glucose cotransporters in the proximal tubule and where are they located? Which is more active?
SGLT2 in early PT
SGLT1 in latter PT
90% reabsorbed by SGLT2
What are the glucose transporters in the proximal tubule? Where are they located?
GLUT2 in early PT
GLUT1 in latter PT
What is an example of counter transport?
Na - H+ exchanger in PT
Where are AQO-1 channels found?
Proximal tubule
How does water permeability vary in different parts of the nephron?
PT - high
Descending LOH - high
Ascending LOH - low
Distal tubule, collecting tubules, collecting ducts - low/high (ADH dependent)
How is chloride reabsorbed?
Transported with sodium due to electrical potential, along paracellular pathway
Na reabsorption = H20 reabsorption = ^ Cl concentration = concentration gradient
Secondary active transport - Na-CL cotransporter
How is urea reabsorbed
Na reabsorption = H2O reabsorption = ^ urea concentration
Urea transporters - inner medullary collecting ducts
How much Na/H2O is reabsorbed in the PT?
65%
How is sodium reabsorbed in different regions of the PT?
First half - cotransport with glucose + amino acids
Second half - reabsorbed with Cl-
What is secreted in the PT?
Bile salts, oxalate, urate, catecholamines
PAH
Drugs/toxins
What are the 3 segments of the LOH?
Thin descending
Thin ascending
Thick ascending
How much water is resorbed in the LOH?
20%
How permeable is the LOH to water?
Descending highly permeable
Ascending impermeable
What is the function of the LOH?
Descending - simple diffusion
Thick ascending - active reabsorption of Na/K/Cl
How is sodium reabsorbed in the thick ascending LOH?
Diffusion gradient maintained by Na-K ATPase in basolateral membrane
Na movement mediated by luminal NKCC2 contransporter (Na + K + 2xCl) - drives K+ reabsorption against concentration gradient
What is the site of action of frusemide?
NKCC2 cotransporter
What substances are absorbed/secreted in the thick ascending LOH?
Na, K, Cl reabsorbed vis NKCC2 cotransporter
Na reabsorbed, H+ secreted via Na-H exchanger
Mg, Ca, Na and K - paracellular absorption - encouraged by positive charge in luminal fluid
What is the reason for the positive charge of luminal fluid in the LOH?
Backless of K+ into lumen
How does the distal tubule function?
First portion - macula densa
Second portion - similar function to thick ascending LOH - diluting segment
Second half - principal cells - Na reabsorption/K secretion
Intercalated cells - secrete or reabsorb H+, HCO3, K
How is sodium chloride absorbed in the distal tubule?
Na-Cl cotransporter on luminal surface
Where do thiazide diuretics act?
Na-Cl cotransporter in distal tubule
What is the action of principal cells and where are they located?
Second half distal tubule
Basolateral Na-K ATPase maintains low Na concentration
Na/K channels facilitate diffusion along concentration gradient (Na in, K+ out)
Where does spironolactone act?
Principle cells of distal tubule
Where does amiloride and triamterene act?
Na channel blockers
Block luminal Na channel in principal cells, reduced activity of basolateral Na-K ATPase
What is the function of type A/B intercalated cells?
A - H+ secretion
B - HCO3 secretion
How do type A intercalated cells act?
Secrete H+ into lumen by H-ATPase and H-K ATPase transporter
H+ generated by carbonic anhydrase, liberating HCO3
HCO3 reabsorbed with HCO3-Cl exchanger
K/Cl leave cell via channels (pg 353)
How do type B intercalated cells act?
Secrete HCO3 into lumen using pendrin - HCO3/Cl exchanger
H+ transported across basolateral membrane with H-ATPase or H-K ATPase cotransporter
Which intercalated cells are involved in K+ reabsorption/secretion?
A - reabsorption
B - secretion
Summarise the function of the late distal and cortical collecting tubule
Impermeable to urea
Reabsorb Na in principal cells under aldosterone control
Type A intercalated cells secrete H+ in acidosis
Type B intercalated cells secrete HCO3 in alkalosis
Permeability to water controlled by ADH
Summarise the function of the medullary collecting duct
Permeability to water controlled by ADH
Permeable to urea + urea transporters - important for formation of concentrated urine
Capable of H+ secretion
How is tubular reabsorption regulated?
Glomerulotubular balance
Peritubular capillary and renal interstitial fluid physical forces
Pressure natriuresis/diuresis
Hormonal - aldosterone, angiotensin, ADH, ANP, PTH
SNS
What is glomerulotubular balance?
Proximal tubular reabsorption increased with GFR - percentage of GFR remains stable at approx 65%
Also happens to smaller degree in LOH
Prevents overload of distal segments at high GFR
How do peritubular capillary and renal interstitial fluid physical forces regulate reabsorption?
Increased arterial pressure = increased peritubular capillary pressure = reduced reabsorption
Increased afferent/efferent arteriole resistance = reduced peritubular capillary pressure = increased reabsorption
Osmotic pressure - higher FF = higher osmotic pressure in peritubular capillaries = more reabsorption
Higher interstitial pressure (due to increased capillary hydrostatic or decreased capillary osmotic pressure) = increased backleak
What is pressure diuresis/natriuresis?
Increased ABP =
1) ^GFR
2) v tubular reabsorption (mechanisms not fully understood)
3) v AngII => v Na reabsorption
4) Internalisation of Na transporters
Where does aldosterone exert its effects on tubular reabsorption? What are they?
Collecting tubule/duct
Increased NaCl + H2O reabsorption
Increased K + H secretion
Where does angII exert its effects on tubular reabsorption? What are they?
Proximal tubule, thick ascending LOH, distal tubule, collecting tubule
Increased NaCl + H2O reabsorption
Increased H+ secretion
Where does ADH exert its effects on tubular reabsorption? What are they?
Distal tubule/collecting tubule and duct
Increased H2O reabsorption
Where does ANP exert its effects on tubular reabsorption? What are they?
Distal tubule/collecting tubule and duct
Reduced NaCl reabsorption
Where does PTH exert its effects on tubular reabsorption? What are they?
Reduced PO4- reabsorption
Increased Ca++ reabsorption
On which cells does aldosterone act? How does it act?
Principal cells of collecting duct
Stimulates Na-K ATPase on basolateral membrane + increased Na permeability of luminal membrane by inserting Na channels
What is the main stimulus for aldosterone secretion?
Increased extracellular K+
Increased angII - (usually associated with sodium/volume depletion or low BP)
What is the body’s main Na-retaining hormone?
AngII
What stimulates AngII formation?
Low BP
What are the actions of angII?
Aldosterone secretion
Efferent arteriole constriction - increases reabsorption, raises filtration fraction => further reabsorption
Directly stimulates Na reabsorption in PT, LOH, DT and CT
How does angII act to stimulate Na reabsorption?
Stimulates basolateral Na-K ATPase pump
Stimulates Na-H exchange on luminal surface (especially proximal tubule)
Stimulates basolateral Na-HCO3 cotransport
Where does ADH bind? How does it act?
V2 receptors in late distal tubule, collecting tubules and collecting ducts
Increases formation of CAMP and protein kinase - stimulates movement of AQP-2 to luminal membrane
Where are AQP 1, 2, 3 and 4 found? Which are controlled by ADH?
AQP -1 - proximal tubular lumen, proximal LOH, not ADH controlled
AQP-2 - luminal - ADH controlled
AQP-3/4 - basolateral, not ADH controlled
What are the effects of chronic ADH increase?
Formation of AQP-2 protein through unregulated gene transcription
What stimulates ANP release? What are it’s actions?
Atrial stretch
Inhibits Na/H20 reabsorption + renin secretion
How does the SNS act to control sodium reabsorption?
If severe - constricts arterioles => reduced GFR
Low levels - act on alpha-adrenergic receptors in tubular epithelium => increased Na reabsorption
What is renal clearance?
The volume of plasma cleared of a substance by the kidneys per unit time
What is the main hormone responsible for controlling urine concentration?
ADH
Describe how osmolality of fluid in the renal tubule changes
Proximal tubule - isosmotic (300)
Descending LOH - very hypertonic (600)
Ascending LOH - hypo osmotic (100)
Distal/collecting tubule
- ADH absent - further dilution (50)
- ADH present - concentration (~600)
What is USG? How does it compare to osmolarity?
Measure of weight of solutes in given volume of urine - determined by number and size of molecules
Osmolarity - number of solute molecules
Describe the steps involved in causing a hyper osmotic renal medullary interstitium
Guyton page 369
Where are the urea transporters located?
UT-A1 + UT-A3 - medullary collecting duct
UT-A2 - thin loop of henle
How is plasma osmolarity estimated?
= 2x(Na) + glucose + urea
Describe the osmoreceptor-ADH feedback system
Water deficit => ^extracellular osmolarity
Osmoreceptor cells in anterior hypothalamus shrink => impulse => posterior pituitary => ADH release => reduced water excretion
Where is ADH synthesised?
Hypothalamus (supraoptic/paraventricular nuclei)
What areas detect osmolarity?
Osmoreceptors - anterior hypothalammus
AV3V region - third ventricle
What are the stimuli for ADH release?
Increased osmolarity
Decreased arterial blood pressure
Decreased blood volume
What stimulates thirst?
Increased extracellular fluid osmolarity
Decreased extracellular fluid volume
Angiotensin II
Dry mouth
GI/pharyngeal stimuli
What factors shift K+ into cells?
Insulin
Aldosterone
B-adrenergic stimulation
Alkalosis
What factors shift K+ out of cells?
Diabetes mellitus
Hypoadrenocorticism
B-adrenergic blockade
Acidosis
Cell lysis
Exercise
Increased extracellular fluid osmalality
Why dp patients with hypoadrenocorticism develop hyperkalaemia?
Reduced cellular K+ uptake
Reduced renal excretion
Summarise renal tubular handling of potassium
65% reabsorbed in proximal tubule
25-30% reabsorbed in LOH (especially thick ascending)
Collecting tubules/ducts - variable, depending on intake
Which cells are most important for regulating potassium excretion?
Principal cells
How do the principal cells secrete K+?
Uptake into cell from Na-K ATPase on basolateral membrane
Passive diffusion into tubular fluid via ROMK and BK channels
What cells are involved in potassium reabsorption/secretion in the distal tubule? Do they reabsorb or secrete?
Principal cells - secrete
Intercalated cells - reabsorb or secrete
Which intercalated cells secrete/reabsorb K+?
Type A - reabsorb
Type B - secrete
What acid-base complication can occur secondary to severe prolonged hypokalaemia
Alkalosis
K reabsorption in Type A intercalated celly - H-K ATPase
What factors increase/decrease tubular secretion of K+?
Increase - increased extracellular potassium, increased aldosterone, increased tubular flow rate
Decrease - acidosis
How do increased ECF K+ levels directly stimulate K+ excretion?
1 - stimulates Na K ATPase activity
2 - increased K gradient to interior of epithelial cell
3 - stimulates synthesis of K channels
4 - stimulates aldosterone secretion
How does aldosterone increase K+ secretion?
Activates Na K ATPase on principal cells
Increases K channels
How is normal potassium excretion preserved during increased sodium excretion?
Increased Na excretion = reduced aldosterone secretion + increased tubular flow
Increased tubular flow => K concentration gradient
=> increased BK channels
How is plasma calcium found?
50% ionised
40% protein bound
10% complexed with anions
How does acid-base status influence plasm calcium?
Acidosis - less bound
Alkalosis - more bound
What is the main method of removal of calcium from the body?
Faeces
How does PTH act to increase serum calcium?
Increases bone resorption
Increases activation of vitamin D and intestinal absorption
Increases tubular reabsorption
Where is calcium reabsorbed in the kidneys?
65% PT
25-30% LOH
4-9% distal/collecting tubules
How is calcium absorbed in the proximal tubules?
Mostly paracellular
20% transcellular - flows into cell down electrochemical gradient (cell has slight negative charge)
Exits cell via basolateral Ca ATPase or Ca-3Na countertransporter
How and where is calcium reabsorbed in the LOH and distal tubule?
Thick ascending loop
50% paracellular
50% transcellular - PTH controlled
Distal tubule - all active transport. Similar process to proximal tubule
What regulates active transport of calcium in the LOH and distal tubule?
Mostly PTH
Vitamin D and calcitonin
Direct action of calcium on CSRs in LOH
What factors increase/decrease renal calcium excretion?
PTH - decrease
Extracellular volume expansion/increased arterial pressure - increase
Increased serum phosphate - decrease
Acidosis - increase
How is renal phosphate excretion regulated?
Overflow mechanism - renal transport maximum for excretion
How does PTH effect phosphorus levels?
Promotes bone resorption => increased phosphorus
Reduces reabsorption => decrease phosphorus
What factors increase renal phosphate excretion?
High dietary phosphate
PTH
Acidosis
Hypertension
What factors decrease renal phosphate excretion?
Low dietary phosphate
1, 25 D3
Alkalosis
T4
How is magnesium distributed in the body?
> 50% bones
49% intracellular
<1% in extracellular fluid
> 50% plasma Mg protein bound
Where is Mg reabsorbed in the kidney?
25% proximal tubule
65% LOH
Mechanism of regulation poorly understood
What factors increase Mg excretion?
High extracellular Mg concentration
High extracellular Ca
Low PTH
High extracellular fluid volume
Acidosis
What factors decrease Mg excretion?
Low extracellular Mg concentration
Low extracellular Ca
PTH
Low extracellular fluid volume
Alkalosis
What are the effects of acute and chronic increases in BP on urinary sodium?
Increases
Efficiency increased with chronic due to suppression of renin release
What actions take place following an increase in sodium intake?
Low pressure reflex receptors - inhibit SNS
Suppression of RAAS
ANP
Pressure natriuresis
What 3 systems defend against changes in H+ concentration? Which is the most powerful?
Buffer systems
Respiratory system
Kidneys***
Where is carbonic anhydrase found?
Alveoli and renal tubules
Describe the bicarbonate buffer system
CO2 + H20 <= => H2CO3
Carbonic anhydrase
H2CO3 <= => H+ + HCO3-
+
Na
With regards to acid base - what is K?
Dissociation constant of an acid
When is a buffer system most efficient?
At pH close to it’s pK
Where is the phosphate buffer system most important?
Intracellular fluid and renal tubular fluid
What are the main elements of the phosphate buffer system?
H2PO4- and HPO4–
What are nonvolatile acids?
Not H2CO3
Cannot be removed by lungs
Where does hydrogen iron secretion and HCO3 reabsorption occur?
All parts of the tubules except depending and ascending thin limbs of LOH
Where is the main site of bicarbonate reabsorption?
80-90% in proximal tubule
10% thick ascending LOH
Remainder distal tubule and collecting duct
How is H+ secreted in the early tubular segments?
Na-H counter transport using Na gradient
What is the net change in H/HCO3 in the early tubular segments?
For every H+ secreted one HCO3 reabsorbed
How is bicarbonate reabsorbed in the proximal tubule/LOH/distal tubule/collecting ducts?
Early proximal tubule - HCO3 - Na cotransporter
Late proximal tubule, thick LOH, distal tubule/collecting duct - Cl - HCO3 exchange
Which cells secrete H+ in the distal and collecting tubules? How do they do it?
Type A intercalated cells
Primary active transport - H-ATPase and H-K ATPase
What facilitates excretion of large amounts of H+ in the urine?
Phosphate and ammonia buffer systems
Describe the phosphate buffer system
Once all bicarbonate in tubules reabsorbed, H+ combines with HPO4–
Excreted as NaH2PO4
How does H+ excretion via the phosphate buffer system differ from the bicarbonate buffer system?
Reflects net gain of HCO3-, rather than replacement of filtered HCO3
Net effect of addition of new HCO£-
Describe the ammonia buffer system
Proximal tubule
Glutamine transported into epithelial cells of proximal tubule, metabolised to 2x NH4+ + 2x HCO3-
NH4+ exchanged for sodium on luminal membrane
Collecting duct
H+ actively secreted, combines with NH3 => NH4
What is the dominant mechanism for H+ excretion during chronic acidosis?
Excretion of NH4+
What factors increase H+ secretion and HCO3 reabsorption?
^PCO2
^H+ / v HCO3
v ECFV
^ AngII
^Aldosterone
v K+
What factors decrease H+ secretion and HCO3 reabsorption?
v PCO2
v H+ / ^ HCO3
^ ECFV
v AngII
v Aldosterone
^ K+
What acid-base abnormality is associated with diuretics and why?
Metabolic alkalosis
1 - Diuretics increase flow in distal and collecting tubules => increased sodium reabsorption in exchange for H+
2 - RAAS stimulation
How long does it take for respiratory compensation to an acid-base abnormality?
6-12 hours
How long does it take for metabolic compensation to an acid-base abnormality?
3-5 days
How is AG calculated? What is considered normal?
Na - HCO3 - Cl
8-16
Where do loop diuretics act? How does this increase urine output?
1-Na, 2-Cl, 1-K co-transporter in thick ascending LOH
Increase quantities of solutes delivered to distal nephron
Disrupt countercurrent multiplier system
Where do thiazide diuretics act>
Na Cl cotransporter in early distal tubule
Where does acetylzolamide act?
Carbonic anhydrase inhibitor
Proximal tubule
Where do mineralocorticoid receptor antagonists act?
Collecting tubule/duct
Where does amiloride act?
Na channel blocker
Inhibit sodium reabsorption and potassium secretion in collecting tubules
What are the potassium sparing diuretics?
Spironolactone - MRA
Amiloride - Na channel blocker
Describe the mechanisms behind the development of bone demineralisation in CKD
Reduced renal conversion of vit D into 1,25- vit D = reduced intestinal calcium absorption
Increased serum PO4 => increased binding of PO4 and Ca => reduced serum ionised calcium => ^PTH
How does Fanconi syndrome manifest?
Increased excretion of amino acids, glucose and PO4
In severe cases - metabolic acidosis, increased excretion of K/Ca, NDI
