Renal Phys Flashcards
Renal Blood FLow
1000 ml/min (~ 20% of cardiac output!)
Kidneys receive highest percentage of cardiac output per gram of tissue
Renal plasma flow (RPF)
Renal plasma flow (RPF) = (1 – Hct) * RBF = 600 ml/min
Assuming hematocrit (Hct) of 40% or 0.4
Glomerular filtration rate (GFR)
Volume of plasma filtered by the kidney per unit time ~ 125 mL/min
Filtration fraction (FF)
Filtration fraction (FF) = GFR / RPF = ~ 20%
Fraction of RPF that is filtered by the kidney
What happens to larger Mw molecules and rest of plasma not filtered by the kidneys
The remaining 4/5th’s of the plasma continues to flow through the renal microvasculature (i.e., efferent arteriole → peritubular capillaries → renal vein)
Plasma osmolarity (Posm) is estimated as:
Posm = 2(Na+) + Glucose/18 + BUN/2.8
- The numbers 18 and 2.8, are adjustments to convert lab values (mg/dL) to (mmol/L).
Osmolar gap
The difference in the measured osmolality vs. the estimated or calculated osmolality
Normal osmolar gap is < ± 10 mOsm/kg water
Do NaCl and mannitol cross cell membranes?
No
Decrease in ECF volume
Volume contraction
Hypoosmotic volume expansion
I.e. SIADH
- ECF osmolarity decreases
- Water shifts from ECF to ICF
- ECF and ICF volumes increase
- Plasma protein concentration decreases
- Hct remains unchanged
Increase in ECF volume
Volume expansion
Hypoosmotic volume contraction
i.e. adrenocortical insufficiency (loss of NaCl)
Examples of Isoosmotic volume contraction
i.e. diarrhea; burns
Examples of hyperosmotic volume contraction
i.e. sweating, fever, DM insipidus
Example of hyperosmotic volume expansion
High NaCl intake
What does an infusion of isotonic NaCl cause?
Isoosmotic volume expansion
Composition of glomerular filtration barrier
- Glomerular fenestrated capillaries
- Basement membrane (contains large negatively charged proteoglycans)
- Podocytes
What glomerular structure is critical in restricting the filtration of albumin?
Podocytes
Podocyte injury or dysfunction underlies most, if not all, proteinuric kidney diseases associated with albuminuria.
Mesangial cells
Support glomerular capillary loops
they secrete extracellular matrix and are contractile cells that can alter GFR by
changing the capillary surface area available for filtration (overall, a minor role in regulating GFR)
How to calculate GFR from ultrafiltration pressure
Why is the hydrostatic pressure of glomerular capillaries higher than all other capillary beds?
PGC is ~ 50 mmHg along its entire length becuase of distal resistance (efferent arteriole)
In normally function kidneys, what is the oncotic pressure in Bowman’s space?
usually 0 becuase of the low filterability of proteins
How does the oncotic pressure within glomerular capillaries change going from afferent to efferent?
Increases as fluid is filtered across into Bowman’s space
In the kidney’s circulation system, where are there a high density of alpha-1 receptors?
Afferent arterioles
Thus, an ↑ in sympathetic nerve activity will ↑ RA and ↓ both RBF and GFR and vice versa.
Low or physiological normal levels of angiotensin II preferentially act on what part of the renal vasculature?
Efferent arteriole to increase its resistance
↓ RBF and ↑ GFR
What can cause a decrease in both RBF and GFR with a greater decrease in RBF due to a large increase in afferent arteriole resistance?
High levels of angiotensin II (i.e. hemorrhage)
What causes preferential vasodilation of the afferent arteriole with an increase in hydrostatic pressure of the glomerular capillary bed and increase in GFR?
Prostaglandins (PGE2 and PGI2)
What population are susceptible to AKI due to NSAID use?
Those w/ kidney disease or low BP
How do renal calculi, BPH, and bladder outlet obstruction affect starling forces of the kidney?
Increases hydrostatic pressure of Bowman’s space and decreases GFR
How does an increase of afferent arteriole resistance affect RPF, GFR, and FF (GFR/RPF)?
RPF = decrease
GFR = decrease
FF = No change
How does an increase of efferent arteriole resistance affect RPF, GFR, and FF (GFR/RPF)?
RPF = decrease
GFR = increase
FF = increase
How does an increase in plasma protein concentration affect RPF, GFR, and FF (GFR/RPF)?
RPF = no change
GFR = decrease
FF = decrease
How does a decrease in plasma protein concentration affect RPF, GFR, and FF (GFR/RPF)?
RPF = no change
GFR = increase
FF = increase
How does a ureter obstruction affect RPF, GFR, and FF (GFR/RPF)?
RPF = no change
GFR = decrease
FF = decrease
What is normal approximate renal blood flow?
20% of CO (~ 1L/min)
How to calculate RBF from renal vascular resistance and pressure gradient between the renal artery and vein?
RBF = ΔP / RVR
Relationship between renal oxygen consumption and sodium reabsorption
Direct positive linear response
Both RBF autoregulation mechanisms act on what?
Myogenic and tubuloglomerular feedback act on the afferent arteriole
Describe the myogenic response to RBF autoregulation
Increase in BP stretch afferent arterioles activating stretch-activated Ca channels and ausing vascular smooth muscle contraction
Most important mechanism of RBF autoregulation when BP > ~ 80 mmHg.
What part of the tobuloglomerular feedback senses delivery of solute and water?
The macula densa
Part of the distal convoluted tubule
What is the site of renin release?
Juxtaglomerular cells - s have a high density of β1 adrenergic receptors
- Also local baroreceptors
- Every nephron has a JG apparatus
Renal vasoconstrictors
- Catechoolamines
- Angiotensin II
- Endothelin
Renal vasodilators
- PGE2
- PGI2
- NO
- Bradykinin
- Dopamine
- ANP
What is the major function of tubuloglomerular feedback?
To maintain constant fluid and Na+ delivery to the distal tubule - where final processing of the urine takes place
Serves to maintain GFR when arterial BP significantly decreases
Which of the following substances is NOT included in the equation to estimate plasma osmolarity?
A. Sodium
B. Glucose
C. Creatinine
D. BUN
C. Creatinine
C. 305 mOsm/L
In the context of renal function, the secretion of a substance implies that:
It is transported from tubular cells into the tubular lumen
A subject in a drug trial was infused with isotonic saline containing 200 mg inulin over a 1-hour period. At the end of the infusion period, plasma inulin concentration had stabilized at 10 mg/L. During the 1-hour infusion period, 100 mg of inulin was excreted in the urine. Use these data to approximate the subject’s extracellular fluid volume:
10 L
A reasonable estimate of the extracellular fluid volume in a 60 kg male is:
12 L
What combination of substances could be used to estimate interstitial fluid volume?
Inulin and Evans blue dye
After a prolonged exercise session, a man drinks 2 liters of water to replenish 2 liters of sweat lost during exercise. Compared to the pre-exercise state, which of the following is true regarding his post-exercise state after consuming 2 liters of water?
ICF volume is greater
D.
Intravenous administration of 1 liter of which of the following fluids would lead to the greatest increase in extracellular volume?
A. 5% dextrose in water
B. 5% dextrose in 0.45% NaCl
C. 0.45% NaCl
D. 0.9% NaCl
E Distilled water
D. 0.9% NaCl
C. Hypoosmotic volume contraction
Adrenal insufficiency
C. Loss of solute-free water
Diabetes insipidus (central - due to TBI)
Diabetes insipidus (central - due to TBI)
Which cell type within the glomerulus is critical for restricting the filtration of large, negatively charged proteins such as albumin?
Podocytes
Under normal conditions, which factor does not play a major role in determining the filtration of substances across the glomerular capillaries into Bowman’s space?
Oncotic pressure in Bowman’s space
D.
What would decrease both renal plasma flow and glomerular filtration rate without changing the filtration fraction?
Increased sympathetic nerve activity (afferent arteriole has a high concentration of alpha-1 receptors)
An increase in sodium delivery to the macula densa would most likely increase the secretion of what?
Adenosine
What is the renal clearance of a substance if its plasma concentration is 10 mg/dL, its urine concentration is 100 mg/dL, and the urine flow rate is 2 mL/min?
20 mL/min
A 25-year-old woman participating in an experiment is found to have a renal para-aminohippuric acid (PAH) clearance of 600 ml/min, a creatinine clearance of 100 ml/min, and a hematocrit of 50%. What is her renal blood flow?
300 mL/min
Which of the following statements is TRUE after a 50% reduction in nephron number? Assume a new steady state is reached after the loss of 50% of nephrons.
the urinary excretion of creatinine will decrease by 50%
A 45-year-old woman is participating in a research study in which GFR is measured using both inulin and creatinine clearance. Which of the following is expected?
A. A higher GFR with inulin clearance because inulin is more freely filtered than creatinine
B. A lower GFR with inulin clearance because inulin is reabsorbed by the tubules
C. A higher GFR with creatinine clearance because creatinine is secreted by the tubules
D. A lower GFR with creatinine clearance because creatinine is reabsorbed by the tubules
C. A higher GFR with creatinine clearance because creatinine is secreted by the tubules
C. Constriction of the efferent arteriole
A.
A PBUN/PCr ratio of > 20:1 in the setting of AKI is suggestive of prerenal AKI (e.g., decreased blood pressure and GFR).
B. 20%
FF = GFR/RPF
What is para-aminohippuric acid used to estimate?
RPF
D. Skeletal muscle mass
X is secreted by the renal tubules
Which transporter is primarily responsible for reabsorbing the majority of glucose in the proximal tubule, and what are its characteristics?
SGLT2 (high-capacity, low affinity)
Toward the end of World War II, Karl Beyer and his associates observed that co-administration of PAH with penicillin decreased penicillin’s urinary excretion. What is the most likely mechanism of this interaction action?
PAH competes with penicillin for tubular secretion
10 mg/dL
What causes the observed “splay” in the glucose titration curve?
Renal physiology
Internephron variability in glucose reabsorptive capacity as the filtered load approaches the transport max.
There is net tubular secretion of substance X
Substance X = PAH
X is reabsorbed to a greater extent than water in the proximal tubule
There is net secretion of drug X
B. Decreased renal tubular secretion
What transporter is responsible for the majority of Na+ reabsorption?
The Na+-H+ antiporter (NHE3) at the beginning of the proximal tubule
D.
Calculate clearance rate
Clearance = urinary excretion/arterial plasma concentration
Urinary excretion = urine concentration x urine flow
What happens to ECF when Na+ is positive
ECF volume will increase
Where does the bulk of Na+ reabsorption occur?
Proximal tubule (67%)
Thick ascending limb (25%)
Where is Na+ reabsorption regulated?
The late distal tubule
Although only accounting for 3% of sodium reabsorption
What happens to the fractional excretion of Na+ (FENa+) with AKI?
The fractional excretion of Na+ increases
because the damaged tubules are not capable of reabsorbing appropriate amounts of Na+
List the four major functions of the proximal tubule
- Reabsorb ~ 67% of the filtered Na+
- Reabsorb ~ 67% of the filtered water
- The tight coupling between Na+ and water reabsorption is called isosmotic reabsorption.
- Is the site of glomerulotubular balance, which couples reabsorption to GFR.
The luminal side of epithelial cells exhibit an extensive brush border, which increases surface area for reabsorption.
What diuretic(s) act on the proximal tubule
Carbonic anyhdrases (i.e. acetazolamide)
What diuretic(s) act on the collecting duct?
K+-sparing diuretics
* Sodium channel blockers (i.e. amiloride)
* Aldosterone receptor antagonists (i.e. spironolactone)
What portion of the nephron does furosemide act on?
The thick ascending loop of Henle
In which site of the nephron is the reabsorption of sodium regulated by aldosterone?
Late distal tubule and collecting duct
What segment is referred to as the diluting segment
The thick ascending limb
Move solutes out of the lumen into the interstitium
Compared to plasma osmolarity, the tubular fluid leaving the thick ascending limb is:
A. Hyperosmotic
B. Isoosmotic
C. Hypoosmotic
C. Hypoosmotic
1.7%
Which segment of the nephron is primarily responsible for reabsorbing approximately 25% of the filtered sodium and creating a lumen-positive potential that contributes to paracellular reabsorption of calcium and magnesium?
Thick ascending limb
A change in which of the following variables most directly signals a change in sodium balance?
A. Ectracellular Na concentration
B. ECF volume
C. Intracellular Na concentration
D. ICF volume
B. ECF volume
Which of the following is an expected physiological effect of an increase in extracellular volume?
A. an increase in peritubular capillary hydrostatic pressure
B. an increase in renin release from JG cells
C. a decrease in arterial baroreceptor firing
D. a decrease in circulating levels of ANP
A. an increase in peritubular capillary hydrostatic pressure
How is chloride reabsorbed in the proximal tubule
Paracellular due to solvent drag and a negative lumen potential
Chloride is primarily reabsorbed in the pars recta of the proximal tubule via the Cl
E. Urea, bicarbonate
About 50% of urea is reabsorbed in the proximal tubule but 67% of water is excreted
What are the major causes of renin release?
- increased sympathetic activity
- Decreased tubular flow rate or NaCl delivery to macula densa
- Decreased renal perfusion pressure
What regulates secretion of ADH?
- Changes in osmolarity (i.e., osmoreceptors) and volume
status (i.e., baroreceptors and cardiopulmonary receptors)
regulate secretion of ADH
What hypothalmic nuclei synthesize and secrete ADH when stimulated?
The supraoptic and paraventricular nuclei of the hypothalamus
Three major actions of ADH
- It increases water permeability of principal cells of the late distal tubule and collecting duct.
- It increases the activity of the NKCC transporter in the thick ascending limb.
- It increases urea permeability in the inner medullary collecting duct, but not the cortical or outer medullary collecting duct
Which of the following changes will produce the strongest stimulus for ADH release from the posterior pituitary?
A. A 1% increase in plasma volume
B. A 1% decrease in plasma volume
C. A 1% increase in plasma osmolarity
D. A 1% decrease in plasma osmolarity
C. A 1% increase in plasma osmolarity
In the presence of elevated plasma ADH levels in a healthy individual, which of the following nephron segments would have the greatest osmolarity in the luminal fluid?
A. Proximal tubule
B. Early distal tubule
C. Thick ascending limb of Henle
D. Thin ascending limb of Henle
D. Thin ascending limb of Henle
Does ADH act on the thin descending limb to increase water permeability?
No
How does ADH impact renal handling of urea?
ADH increases urea reabsorption in the inner medullary collecting duct
The osmolarity of the fluid in the renal medullary interstitium would exceed urine osmolarity
Which of the following would not hinder the ability of the kidney to produce a concentrated urine?
A. An osmotic diuretic
B. A loop diuretic
C. Rx that decreases medullary blood flow
D. Rx that decreases transport in the inner medullary collecting duct
C. Rx that decreases medullary blood flow
A patient’s urine is collected for 120 minutes. The urine volume is 600 ml, urine osmolarity is 150 mOsm/L, and plasma osmolarity is 300 mOsm/L. What is the “free-water” clearance?
+ 2.5 ml/min
Which of the following is a potenetial cause of hyponatremia?
A. SIADH
B. Hyperaldosteronism
C. Central diabetes insipidus
D. Nephrogenic diabetes insipidus
A. SIADH
D. Early/mid distal convoluted tubule
Regardless of ADH concentration/activity
D. Urea
Desmopressin is a V2 agonist
Whereas vasopressin acts on both V1 and V2 receptors
A. Central diabetes
How is nephrogenic diabetes insipidus Tx’d?
Thiazide diuretics
C.
Hypervolemic hyponatremia - hypervolemia causes ANP/BPN which causes sodium excretion (natriuretic peptides)
What type of volume and sodium status is present w/ SIADH
Euvolemic hyponatremia
Hypervolemia is transient - ANP/BNP activates to excrete sodium
D.
What cells Monitor sodium chloride concentration of fluid within the distal tubule / distal convoluted tubule
Cells of the macula densa
This is an electron micrograph from the filtration apparatus in the kidney. A predominant protein associated with the structure labeled at 6 would be
Collagen IV
The arrow at 4 in the accompanying image indicates a portion of what specific cell type? Hint: Bowman’s space (that is the urinary space) is labeled at 1.
Glomerular capillary endothelial cell
ID and list characteristics of tissue
Transitional epithelium
* may be binucleate
* may have polyploid nuclei
* Stem cells are located in the basal regions
* forms tight seals to prevent water loss
The accompanying image is a scanning electron micrograph of structures in cortex of the kidney. The arrow at 1 points to a(n):
Interlobular (cortical-radial) artery
The red arrows in this image from the renal cortex point to?
The parietal layer of Bowman’s capsule
The structure labeled at 1 in the accompanying image from the renal cortex is a?
Proximal convoluted tubule
The structure labeled at 2 in the accompanying image of the renal medulla is a profile of?
Collecting duct
Which cell type might you expect to show an increase in number and in phagocytic activity as a result of the glomerulonephritis?
Intraglomerular mesangial cell
A post-menopausal woman presents with anemia. Her diet appears adequate and her nutritional state is normal. She has a BMI of 26. What cell type in her kidneys that are a source of erythropoietin, might be expected to have reduced synthetic and / or secretory activity that could explain her anemia?
Interstitial cells surrounding peritubular capillaries
Histological differences between PCT and DCT
-DCT cells are smaller and stain less eosinophilic than PCT
-Brush border less apparent compared to PCT
Where are JG cells located
In the afferent arteriole
What is the only example of fenestrated capillaries in the human body?
Glomerular capillaries
What is the predominate protein of the lamina densa?
What cells synthesize the lamina densa?
- Collagen IV
- Podocytes and glomerular capillary endothelium
What cells are the phagocytic cells of the glomerular basement membrane?
Intraglomerular mesnagial cells
Derived from smooth muscles
What type of fluid level changes is seen in central diabetes insipidus?
Hyperosmotic fluid contraction
What would result in an increased GFR and RPF while maintaining FF?
Dilation of afferent arteriole
Difference between clearance of inulin vs. PAH:
PAH - filtered and secreted
Inulin - only filtered
What part of the nephron is hypoosmotic relative to plasma osmalality?
The early distal convoluted tubule
285 mOsm/kg
Mr. McGee is a 45 year old male who is following up for routine labs. He has a history of poorly controlled diabetes. You notice his sodium is 131 mEq/L, and his glucose is 350 mEq/L. What is his corrected sodium?
135 mEq/L
Mr. Torres is a 38 year old male who has been admitted to the hospital for treatment of symptomatic hyponatremia. His sodium is 117 mEq/L. You start treatment with boluses of hypertonic saline. By how much should you try to raise his sodium with hypertonic saline in the immediate setting in order to improve his symptoms?
4-5 mEq/L
In treatment of chronic hyponatremia, what is the maximum amount the sodium should be increased in a 24 hour period to avoid osmotic demyelination syndrome?
8 mEq/L/24 hours
Mr. Mallard is an 85 year old male who is brought from the nursing home with a previous history of stroke, aphasia, and hemiparesis who is brought to the ER for altered mental status. The nurses told EMS that he has made almost no urine over the past 24 hours and has had little oral intake. He has not had any other symptoms. He has a previous history of hypertension but is not currently on any medications for this. His initial labs are significant for a sodium of 158 mEq/L. What is the most likely cause of his hypernatremia?
Reduced water intake
Titrate sodium down over 48 hour period
A. Hyperglycemia
C. Hypertriglyceridemia
E. Elevated creatanine
C. Hypotonic
D. Urine [Na+] < 20 mEq/L
F. His ADH level is low
H. His V1 receptros are being stimulated
D. 0.9% saline
A. Alcohol use (beer potomania)
C. Fluoxetine
E. Chlorthalidone
F. Non-compliance w/ fluid restriction
Thiazides are more likely to cause hyponatremia than loop diuretics
Beer potomania is an exception to hypo/hypernatremia being due to a free-water problem (it’s a NaCl intake problem)
A. Chest CT
To r/o small cell carcinoma due to smoking Hx
B. Hypertonic saline
E. Start 5% dextrose (D5W)
Change in serum sodium conc. of 13 mEq/L - will cause osmotic demylenation in 1-2 days if not corrected (a change of 8 mEq/L/day is max.)
D. Lithium
Lithium can cause diabetes insipidus - hypernatremia
A. Plasma sodium of 157 mEq/L
D. Urine osmolality of 200 mOsm/L
E. Plasma osmolality of 318 mOsm/L
5.8 L
Water deficit (L)=Current TBW x (plasma [Na]-140)/140
In response to a sudden decrease in plasma calcium, what is the source for most of the calcium that restores plasma levels to normal
Bone
The majority (99%) of calcium in the body is located in bones. It can be rapidly mobilized from bone to serum in response to a sudden decrease in plasma calcium.
What do increased FGF23, PTH, ECF volume, and acidosis have in common?
Think electrolyte imbalance
They lead to decreased phosphate levels
All of these factors increase urinary excretion of phosphate. FGF23 and PTH directly inhibit phosphate reabsorption in proximal tubules. Acidosis increases phosphate excretion by shifting the balance of HPO42- to H2PO4 which is not as extensively reabsorbed compared to HPO42- in the proximal tubule. ECF expansion decreases sodium reabsorption in the proximal tubule. Because phosphate reabsorption is tied to sodium reabsorption, more is excreted.
Where is the majority of filtered magnesium reabsorbed?
The majority of filtered magnesium is reabsorbed in the thick ascending limb via a paracellular route.
During normal or high potassium intake, potassium excretion is regulated by:
potassium secretion in the distal nephron.
The distal nephron both reabsorbs and secretes potassium. During normal or high intake of potassium, secretion in the distal tubule and collecting duct (principal cells) is required to maintain external potassium balance.
For which substance is it possible to excrete more than is filtered?
A. Sodium
B. Potassium
C. Chloride
D. None of the above
B. Potassium
Even under conditions of major natriuresis, most of the filtered sodium and chloride is reabsorbed, but with a high potassium load, high secretion in the distal nephron can lead to more potassium excretion than filtration.
A key role of “BK” potassium channels in the kidney is to?
help the body excrete potassium in response to very large loads.
BK potassium channels in the distal nephron are activated during high tubular flow rates to assist in the excretion of large potassium loads.
An increase in K+ intake usually causes a small increase in ECF levels, which is a major stimulus for the release of?
Aldosterone
Aldosterone stimulates K+ secretion via ROMK channels in principal cells. K+ reabsorption will be minimal in alpha-intercalated cells. K+ concentration in the ECF is low and will not affect ECF volume.
PTH’s action on the renal tubule leads to an increase in what secondary messenger?
cAMP
PTH acts on the renal tubule by stimulating adenyl cyclase and generating cAMP. The major action of the hormone are inhibition of phosphate reabsorption in the proximal tubule, stimulation of Ca2+ reabsorption in the distal tubule, and stimulation of 1,25-dihydroxycholecalciferol production. PTH does not alter the renal handling of K+.
A patient with chronic kidney disease develops secondary hyperparathyroidism. Which finding would be consistent with secondary hyperparathyroidism?
Hypocalcemia
Secondary parathyroidism in patients with chronic kidney disease results from impaired ability to excrete phosphate, decreased intestinal calcium absorption, and increased binding of ionized calcium and phosphate. It is associated with hyperphosphatemia, hypocalcemia or low-normal levels of calcium, and increased FGF23 levels.
Which segment of the nephron does parathyroid hormone primarily regulate calcium reabsorption?
Distal tubule
In the nephron, PTH decreases the reabsorption of which of the following electrolytes or minerals from the tubular lumen?
A. Magnesium
B. Phosphate
C. Potassium
D. Calcium
B. Phosphate
Hypercalcemia
Acidemia
Insulin
Hypokalemia
At which site of the nephron is potassium handling regulated by aldosterone?
Late distal tubule
Fibroblast growth factor 23 (FGF23) increases phosphate (reabsoption/secretion)
Fibroblast growth factor 23 (FGF23) increases phosphate excretion
B. β2 adrenergic receptor stimuluation
G. Intracellular shift of potassium
“Internal potassium balance”
β2 adrenergic receptor stimuluation increases activation of sodium-potassium ATPase increasing intracellular potassium
A.
Increase [K+] in collecting duct due to high potassium consumtion as oral supplement (excreted by ROMK channels in principal cells)
Factors that affect external potassium balance
Most important cell = principal cell - secretion of potassium through ROMK channels of the distal tubule
A.
Where is one-alpha hydroxylase primarily located in the nephron?
The proximal tubule is the primary site for 1-alpha hydroxylase activity, where the enzyme converts 25-hydroxyvitamin D into its active form, calcitrio
In CKD = decrease number of functional nephrons = decrease in functional proximal tubule cells
What tissue is FGF23 released from?
Bone
Inhibits phosphate reabsorption in the proximal tubule
also inhibits one-alphahydroxylase
What diuretic increases calcium reabsorption in the distal tubule?
Thiazides
