Pulm/Renal - Physiology - Body Fluids; Renal Hemodynamics, GFR, & Clearance; the Nephron Flashcards
A 20-year-old, unresponsive woman is brought to the ED with respiratory distress after ingesting ‘ecstasy’ and subsequently drinking large amounts of fluid.
Her lab results are shown below. Explain why she has these results.
Electrolytes:
- Na+ — 117 mmol/L*
- Cl- — 87 mmol/L*
- HCO3- — 15 mmol/L*
Serum osmolarity: 245 mOsm/kg
Urine specific gravity: 1.015
Her large intake of fluid has (due to dehydration and extreme thirst caused by ecstasy) has diluted out her electrolytes, so all are low, and her fluids are extremely dilute
In a healthy adult, what percentage of the body is typically made up by adipose?
What is the rest classified as?
20% (men: 10 - 20; women: 18 - 25);
lean body mass (80%)
How many liters of water are found in the average healthy 70 kg individual?
How much of this is intracellular? Extracellular? Plasma?
40 L;
25 L
15 L (11.5 L interstitial; 3.5 L plasma)
What is the 60-40-20 rule of thumb for fluids?
60% of body weight
40% intracellular
20% extracellular
What is the state of the water in the interstitium?
It is gel-like (combined with ground substance and other extracellular materials)
What term describes excess fluid in the interstitial space?
Edema
What proportion of lean body mass is water?
What percentage of a healthy individual is made up by lean body mass (non-adipose tissues, including water)?
73%;
80%
Body fat = Total weight - ____________________.
Lean body mass = total body water / _____.
Lean body mass;
0.73
Calculate the lean body mass and adipose fraction for the following patient.
5’4 woman
91 kg weight
40 L water
40 L / 0.73 = 54.8 L lean body mass
91 - 54.8 = 36.2 kg fat
36.2/91 = 40% adipose
Obesity can be defined by an individual’s adipose content (as a fraction of weight).
What percentage defines obesity in a man?
What percentage defines obesity in a woman?
≥ 25%
≥ 32%
What proportion of body water is intracellular?
What proportion is extracellular?
Of the extracellular, what proportion is plasma?
~2/3
~1/3
~1/4
The quantity of a substance in fluid is equal to the volume of fluid multiplied by:
The concentration of the substance
(Quantity = volume * concentration)
Evans blue dye is a substance that binds plasma proteins.
You administer 10 mg into an 80 kg patient’s bloodstream and remove a sample 10 min later. The evans blue dye concentration of the sample is 0.4 mg / 100 mL.
What is the plasma volume of the individual?
What is the blood volume of the individual?
Quantity administered = volume * concentration
10 mg = V * 0.4 mg / 100 mL
10 mg / 0.4 mg / 100 mL = V = 2500 mL
Plasma volume / fraction of plasma in the blood = blood volume
2500 mL / 0.55 = 4546 mL
What body fluid compartment volumes can be directly measured?
Which can only be indirectly measured?
Total body water,
ECF, plasma, blood volume;
ICF,
interstitial fluid
What substance can be used to measure total body water?
What substance can be used to measure ECF?
What substance can be used to measure blood volume?
What substance can be used to measure plasma volume?
D2O
Inulin
Radiolabeled iron
Radiolabeled albumin
How is the anion gap measured?
Cations - anions
(Na+ + K+) - (Cl- + HCO3-)
Calculate the anion gap for the following electrolytes.
Na+ — 117 mmol/L
Cl- — 87 mmol/L
HCO3- — 15 mmol/L
K+ — 4 mmol/L
(117 + 4) - (87 + 15) = 19
Besides electrolyte abnormalities, what might cause a change in the anion gap?
A change in organic anion concentrations (e.g. protein, ketones, etc.)
A 20-year-old, unresponsive woman is brought to the ED with respiratory distress after ingesting ‘ecstasy’ and subsequently drinking large amounts of fluid.
Her lab results are shown below. What is your diagnosis?
Electrolytes:
- Na+ — 117 mmol/L*
- Cl- — 87 mmol/L*
- HCO3- — 15 mmol/L*
Serum osmolarity: 245 mOsm/kg
Urine specific gravity: 1.015
Hyponatremia;
cerebral and pulmonary edema
(hypoosmolar syndrome)
What is the normal serum osmolality?
True/False. It is not a colligative property.
290 mOsm/kg;
false
What is a severe consequence of body hypoosmolality?
Cerebral edema (and eventual death)
Describe how each of the following will impact the ECF:
- An infusion of hypotonic fluid
- An infusion of isotonic fluid
- An infusion of hypertonic fluid
- Expands by less than the volume infused
- Expands by the volume infused
- Expands by more than the volume infused
How is the renal fraction calculated?
What is it normally?
Renal blood flow / cardiac output
20%
True/False.
The kidneys use up virtually 100% of the oxygen they receive.
False.
The kidneys actually use very little of the oxygen coming in and there is some shunting of oxygen through the arteriovenous system
True/False.
The renal arterial system is non-anastomotic, and it is easy for small segments to be infarcted.
True.
True/False.
Albumin’s size is the main reason it doesn’t leave the glomerulus through the filtration slits.
False.
Its charge is the main reason it doesn’t pass through
Protein loss in the urine will happen either because of loss of the _____________ or a widening of the ____________.
Charge barrier;
filtration slits
Renal resistance happens in which vessels?
The arteries, afferent arteriole, and efferent arteriole
The glomerular filtration rate is maintained at a high pressure to overcome what pressure that would keep fluid in the glomerulus?
The colloid osmotic pressure
(hydrostatic pressure - osmotic pressure)
What is the average GFR?
What is the average renal blood flow?
125 mL / min (180 L / day);
1200 mL / min
What are the three intrinsic mechanisms of renal blood flow control?
Autoregulation (myogenic)
Tubuloglomerular feedback (tubular pressures increase –> glomerular pressure increases in response)
Paracrine factors
What are the main extrinsic mechanisms of renal blood flow control?
Sympathetic nerves
Hormones (including ANP)
Which are the vasoconstricting hormones affecting renal blood flow?
Epinephrine
Angiotensin II
Endothelin
Which are the vasodilating hormones affecting renal blood flow?
Prostaglandins
Bradykinin
Atrial natriuretic peptide
Nitric oxide
Does angiotensin II affect glomerular filtration or systemic arteriolar constriction?
Both
In what electrolyte circumstance is an NSAID more likely to decrease GFR?
Sodium-depleted circumstances
(increased vasoconstriction effect)
Atrial natriuretic peptide causes a decrease in the release of what two other hormones?
What effect does ANP have on the vasculature?
Renin,
aldosterone;
renal vasodilation
What effect do tubuloglomerular feedback and autoregulation have on renal blood flow?
What effect do they have on GFR?
Both maintained during fluctuations in arterial pressure
What effect does the renin-angiotensin system have on renal blood flow?
What effect do they have on GFR?
Reduces both
What substance partially counteracts the effects of angiotensin II?
Prostaglandins
Via what clearance equation is GFR calculated?
Clearancex = Urine flow * Urinex / Plasmax
True/False.
In order for a substance to be useful in calculating GFR via the clearance equation, it must be:
freely filtered at the glomerulus,
not reabsorbed or secreted,
not metabolized or degraded,
easily measured.
True.
What are some endogenous substances that can be used for measuring GFR?
Inulin;
mannitol;
radiolabeled compounds
Calculate the GFR for the following patient using the results of this 24-hour urine collection:
1.6 L urine
Urine creatinine 105 mg / dL
Plasma creatinine 0.9 mg / dL
130 ml/min
((1600 mL / 24 hours / 60 min) * 105 mg / dL) / 0.9 mg / dL
The plasma concentration of what substance is a good indicator of their GFR?
What is a normal value for this substance?
Creatinine;
1 mg/dL
If the plasma creatinine level is 1, what does this indicate about the glomerular filtration rate?
If it increases to 2, what does this indicate?
If it increases to 3, what does this indicate?
If it increases to 4, what does this indicate?
Normal GFR (~120 mL/min) (i.e. 100%/1)
GFR down to 50% (~60 mL/min) (i.e. 100%/2)
GFR down to 33% (~40 mL/min) (i.e. 100%/3)
GFR down to 25% (~30 mL/min) (i.e. 100%/4)
What would a plasma creatinine concentration of 5 roughly indicate about GFR?
A GFR of 24 mL/min (normal: 120 mL/min)
(100% function / 5)
Calculate the GFR for the following patient using the results of this 24-hour urine collection:
Urine flow: 3 mL/min
Urine inulin 9.5 mg / mL
Plasma inulin 0.26 mg / mL
110 mL/min
(UF * Ux)/Px
If calculating GFR via renal plasma flow, what equation would be used?
Renal plasma flow = (Urine flow * Urinex) / (Pa(x) - Pv(x))
What is a useful substance for calculating GFR via renal plasma flow?
Why?
Para-aminohippurate;
it is fully secreted
True/False.
Measuring GFR via clearance necessitates a substance that is fully filtered.
AND
Measuring GFR via renal plasma flow necessitates a substance that is neither secreted nor reabsorbed.
False.
- Measuring GFR via renal plasma flow necessitates a substance that is fully filtered (e.g. para-aminohippurate).*
- AND*
- Measuring GFR via clearance necessitates a substance that is neither secreted nor reabsorbed (e.g. inulin).*
If a substance’s clearance is less than the GFR, what does this indicate?
There is net reabsorption
If a substance’s clearance is greater than the GFR, what does this indicate?
There is net secretion of the substance
If a substance’s clearance is less than the GFR, what does this indicate?
If a substance’s clearance is greater than the GFR, what does this indicate?
Net reabsorption;
net secretion
Where does the majority (67%) of filtered sodium and water get reabsorbed in the nephron?
Where does the next 25% get reabsorbed?
And the final 7 - 8%?
The proximal convoluted tubule;
the loop of Henle;
the DCT/collecting duct
True/False.
< 1% of filtered water and sodium actually gets excreted in the urine.
True.
Describe the relative amounts of sodium and water reabsorbed in each part of the nephron.
Which portion of the nephron is known as the ‘bulk reasborber?’
The proximal convoluted tubule
Basolateral Na+/K+ ATPases maintain a low sodium concentration in the proximal tubular cells.
What process does this facilitate and of what substances?
Apical reabsorption via sodium-linked cotransport;
glucose, amino acids, lactate, citrate, succinate, etc.
Via what mechanism is sodium maintained at a very low concentration in proximal tubule cells so that a gradient exists for sodium-linked cotransport of a variety of organic anions and other substances?
Basolateral Na+/K+ ATPases
What type of inhibition exists between solutes vying for position with the sodium-solute cotransporters in the PCT lumen?
Competitive inhibition
What will happen to PCT reabsorption during ATP-depletion?
It decreases due to decreased Na+/K+ activity
Normal plasma glucose is about:
Normal urine glucose concentrations are about:
Glucose is reabsorbed until what concentration?
100 mg/dL
0 mg/dL
375 mg/dL
Is most organic anion reabsorbtion in the PCT by passive or active transport?
What is the main form of transport used?
Active;
sodium-linked cotransport (secondary active transport)
Is sodium-linked cotransport active or passive transport?
Active (secondary)
Is urea actively or passively reabsorbed in the nephron?
An increase in what will increase urea excretion (i.e. what will decrease reabsorption)?
Passively;
urine flow rate
How is phosphate reabsorbed in the PCT?
Actively
(sodium cotransport)
What sodium exchanger is present at the PCT basolateral surface?
What cotransport is present at the PCT apical surface?
What sodium exchanger is present at the PCT apical surface?
Na+/K+ ATPase
Sodium-linked cotransport
Na+/H+ ATPase
Where does most Cl- reabsorption happen in the nephron?
How?
The late PCT;
the Cl- level builds up and then passively flows down its gradient (between the cells)
True/False.
Na+/H+ exchangers in the nephron alkalize the tubular lumen and increase bicarbonate reabsorption by making the lumen more positive.
False.
Na+/H+ exchangers in the nephron acidify the tubular lumen and increase bicarbonate reabsorption by making the lumen more negative.
What effect does passive Cl- reabsorption in the late proximal tubule have on Na+ reabsorption?
The tubular lumen becomes more positive, driving Na+ out passively
Sodium reabsorption in the early PCT is:
Sodium reabsorption in the late PCT is:
Secondary active (sodium-linked cotransport)
Passive (following Cl- loss)
Chloride in the PCT can be exchanged (1:1 exchange) into the tubular cells for any of what three bases?
OH-
HCO3-
Formate
In the PCT, chloride ions can be exchanged for bases (formate, OH-, HCO3-). What happens to these bases once they are in the tubule lumen?
They bind hydrogen ions and diffuse back into the cells
Bases (OH-, formate, HCO3-) can be exchanged for Cl- reabsorption in the PCT.
H+ can be exchanged for Na+ reabsorption in the PCT.
Are all of these bases and H+ then excreted?
No;
they combine (neutralizing charge) and diffuse back into the cells
Which image depicts NaCl reabsorption in the early PCT?
Which image depicts NaCl reabsorption in the late PCT?
2;
1
Describe how HCO3- is reabsorbed in the PCT at the apical membrane.
Na+/H+ exchangers pump hydrogen into the tubular lumen.
The H+ and HCO3- form H2CO3.
Tubular carbonic anhydrase forms CO2 and H2O, which then diffuse into the cells.
Cellular carbonic anhydrase then recreates HCO3-.
In the PCT lumen, after HCO3- is turned first into H2CO3 and then CO2 / water, what happens next?
The CO2 and H2O diffuse into the cell and carbonic anhydrase recreates H2CO3.
HCO3- is then cotransported with Na+ and also exchanged for Cl- at the basolateral cell membrane.
A.
B.
C.
True/False.
The PCT is not very soluble to water.
False.
It is very soluble to water (via apical and basolateral aquaporins).
Why does solute not concentrate in the tubular cells and interstitium as solute is reabsorbed in the PCT?
The capillary movement continuously whisks the solute and fluid away
B.
You administer 1 L of isotonic saline to a patient. What effect does this have on their blood osmolality?
It decreases
(diluted plasma proteins)
Describe the Starling mechanism of the nephron.
If a patient’s blood osmolality is low, less fluid will be drawn from the renal interstitium to the capillaries.
Fluid builds up in the interstitium, weakening tight junctions and allowing H2O/Na+/Cl-/HCO3- to reenter the PCT lumen for excretion
B.
What are the two types of nephron (based on anatomical location)?
What is the distinction?
Cortical, juxtmedullary (7:1 ratio);
the length of their loops of Henle
What are the three portions of the loop of Henle?
Thin descending
Thin ascending
Thick ascending
Describe the thin descending loop of Henle.
Highly permeable to H2O, urea, NaCl, etc.
No active NaCl transport
Describe the thin ascending loop of Henle.
NO PERMEABILITY TO H2O
Highly permeable to urea, NaCl, etc.
No active NaCl transport
Describe the thick ascending loop of Henle.
Active NaCl transport
No permeability to H2O
Which portion of the loop of Henle is the concentrating portion?
The descending limb (thin)
Which portion of the loop of Henle is the diluting portion?
The ascending limb (thin and thick)
Where in the loop of Henle can NaCl/urea/solutes be passively reabsorbed?
Where in the loop of Henle can H2O be reabsorbed?
Where in the loop of Henle can NaCl be actively reabsorbed?
The entire loop;
the descending limb;
the thick ascending limb
True/False.
The concentration of the urine is largely decided by activity in the loop of Henle.
True.
A.
B.
A.
B.
C.
D.
(Select all that apply)
B.
D.
A.
B.
C.
Describe active reabsorption in the ascending loop of Henle.
Basolateral membrane: Na+/K+ ATPases maintain low Na+ in the cell.
Apical membrane: The Na+/Cl-/K+ cotransporter brings in 1 Na+, 1 K+, and 2 Cl- all at the same time.
What does furosemide do in the nephron?
Where?
Blocks Na-K-Cl cotransport in the ascending loop of Henle
What form of passive Na+ reabsorption occurs in the thick ascending limb of the loop of Henle?
K+ is brought into the cell by Na-K-Cl cotransport.
The K+ diffuses back out into the lumen via leak channels.
The lumen becomes +10 mV.
This charge drives Na+ out of the lumen via passive, transcellular pathways.
(In the nephron)
A.
B.
A.
True/False.
The renal cortex and medulla have similar intersitial tonicities.
False.
The medulla is hypertonic when compared with the cortex
Why does H2O passively leave the loop of Henle in the thin descending limb?
It follows the corticomedullary osmolality gradient
ADH acts on which portions of the nephron?
The late DCT and the collecting duct
A.
B.
C.
D.
What is the ‘single effect’ in the countercurrent multiplier system?
What is the single effect osmolality change?
The thick ascending limb pumps Na+ out into the intersitium, diluting the fluid sent to the DCT
(in the image, loop of Henle 1 is basically being turned into loop of Henle 2);
this is a ~200 mOsm/kg difference.
A.
C.
D.
A.
B.
C.
At its deepest point, what is the osmolality of the lumen of the loop of Henle?
At its deepest point, what is the osmolality of the vasa recta?
1200 mOsm/kg
1200 mOsm/kg
C.
D.
What three solutes play the biggest role in urine concentration?
Na+, Cl-, and urea
Where are the only locations in the nephron where urea reabsorption occurs?
The PCT (50%);
the collecting duct of the inner medulla
Is urea reabsorbed in the outer medullary portion or the inner medullary portion of the collecting duct?
Inner medullary portion
True/False.
Some urea that is reabsorbed in the collecting duct (in the inner medullary portion) will be secreted into the loop of Henle to affect countercurrent multiplication.
True.
True/False.
Urea is responsible for 40% of medullary interstitial osmolality, meaning that the higher NaCl concentration in the loop of Henle provide a chemical gradient to drive NaCl out into the interstitium, even though the intersititum’s total osmolality is higher.
True.
A.
B.
C.
Where is the macula densa located?
At the junction of the (1) thick ascending limb of the loop of Henle and (2) the DCT
What are the two halves of the distal tubule of the nephron?
The early D.T. (DCT) and the late D.T. (connecting tubule)
What is the main purpose of the early distal tubule of the nephron?
What is the main purpose of the late distal tubule of the nephron?
NaCl reabsorption;
NaCl and H2O reabsorption
What type(s) of cell line(s) the early distal tubule of the nephron? What are the functions?
What type(s) of cell line(s) the late distal tubule of the nephron? What are the functions?
Distal tubule cells (NaCl reabsorption);
connecting tubule cells (NaCl + H2O reabsorption),
intercalated cells (H+ secretion)
- What type of cell in the distal tubule is responsible for NaCl and H2O reabsorption? Early or late distal tubule?
- What type of cell in the distal tubule is responsible for only H+ secretion? Early or late distal tubule?
- What type of cell in the distal tubule is responsible for only NaCl reabsorption? Early or late distal tubule?
Collecting tubule cells (late, 75% of late);
intercalated cells (late, 25% of late);
distal convoluted cells (early, 100% of early)
What are the three sections of the collecting duct in the nephron?
Cortical,
outer medullary,
inner medullary
What are the two main cell types in the collecting duct?
Describe the changes in cell type concentrations found in the cortical CD vs. the outer medullary CD vs. the inner medullary CD.
Principal cells;
intercalated cells
- (CCD - 75:25*
- OMCD - 80:20*
- IMCD - 99:1)*
What is the function of collecting duct principal cells?
What is the function of collecting duct intercalated cells?
NaCl and H2O reabsorption, K+ secretion;
H+ secretion
Via what mechanism do distal convoluted cells absorb NaCl?
Apical Na+/Cl- cotransport;
basolateral Na+/K+ ATPases
What type of transmembrane protein structure is abundant on the basolateral membranes of cells of the nephron?
It maintains intracellular Na+ concentrations at a very ____ level.
Na+/K+ ATPases;
low
How do thiazide diuretics (e.g. hydrochlorothiazide) affect the kidney?
They block Na+/Cl- cotransport in the early distal convoluted tubule
C.
(remember, these are separate from the connecting tubule cells and intercalated cells of the late distal tubule)
Describe the electrolyte transport of *collecting tubule cells (late distal tubule) and *principal cells (of the collecting duct).
*Note: these can be considered virtually identical for our purposes.
(Note: chloride is reabsorbed through the transcellular space)
Where does potassium secretion occur in the nephron?
Via what type(s) of cell?
In exchange for what ion?
The late distal tubule and collecting duct;
collecting tubule cells, principal cells;
Na+
Describe the ion transport of intercalated cells in the nephron.
True/False.
Chloride reabsorption in the nephron often follows sodium reabsorption because the loss of sodium leaves a slightly positive charge in the tubules.
False.
Cl- reabsorption in the nephron often follows Na+ reabsorption because the loss of Na+ leaves a slightly negative charge in the tubules.
B.
ADH causes water reabsorption in what tubules?
The collecting tubule (late distal tubule) and the collecting duct
Why does urea leave the collecting duct to the inner medulla?
ADH concentrates the fluid so there is a high [Urea] the time it reaches the inner medulla portion
In the late distal tubule and the collecting duct
A.
B.
What are the three mechanisms regulating late distal tubule and collecting duct Na+ reabsorption?
- Tubular flow
- Plasma [K+]
- Aldosterone
Why can drugs like furosemide cause hypokalemia?
Furosemide increases loop of Henle tubular Na+, thus increasing K+ secretion in the late distal tubule and collecting duct
(see principal cells in image)
Describe the tubular flow mechanism regulating late distal tubule and collecting duct Na+ reabsorption.
Since this portion utilizes Na+ and K+ leak channels, increased Na+ delivery (increased tubular flow) causes increased Na+ reabsorption and K+ secretion
Describe the plasma [K+] mechanism regulating late distal tubule and collecting duct Na+ reabsorption.
Increased plasma [K+] causes increased basolateral Na+/K+ ATPase activity and increased Na+ reabsorption and K+ secretion
Describe the aldosterone mechanism regulating late distal tubule and collecting duct Na+ reabsorption.
(1) Increased insertion of Na+ channels into the apical membrane;
(2) increased insertion of Na+/K+ ATPases into the basolateral membrane
How does aldosterone get into the renal cells?
Its effects are then on ________ receptors.
Simple diffusion (its a steroid hormone);
nuclear (affecting transcription)
A.
B.
C.
D.
A.
D.
What makes ADH and oxytocin so similar that they are both synthesized in the hypothalamus (paraventricular and supraoptic nuclei)?
Their structures are very similar.
What receptor does ADH bind on the basolateral surface of nephron cells?
What is the effect?
V2;
protein phosphorylation and aquaporin2 insertion into the apical membrane
Which aquaporin is inserted into the apical membrane of the collecting tubule and collecting duct when ADH is present?
Which aquaporins are present on the basolateral membrane regardless of ADH presence?
Aquaporin2;
aquaporin3, aquaporin4
A.
C.
D.
What are the main two factors regulating ADH release?
- Plasma osmolality (hypothalamic osmoreceptors)
- Blood volume (atrial stretch receptors)
C.
A.
E.
