What percent of body weight is TBW?
-60%
Two divisions of TBW? Percent contribution?
-intracellular (2/3)
-extracellular (1/3)
Major cations of the ICF?
-K+
-Mg+
Two components of the ECF? Percent contribution?
-interstitial fluid (3/4)
-plasma (1/4)
Major cation of the ECF?
-sodium
Major plasma proteins?
-albulin and globulins
What is the 60-40-20 rule?
-60% of body fluid is TBW
-40% of body fluid is intracellular fluid
-20% of body fluid is extracellular fluid
What is used as a marker for TBW?
-titrated water
What is used as a marker for ECF?
-mannitol
What is used as a marker for plasma volume?
-evans blue
List three conditions that result in volume contraction.
-diarrhea
-lost in desert
-adrenal insufficiency
List three conditions that cause volume expansion.
-infusion of isotonic NaCl
-excessive NaCl intake
-SIADH
What occurs during infusion of isotonic NaCl?
-ECF volume increases
-no change in osmolarity of ECF or ECF
-plasma protein concentration and Hct decrease
-arterial blood pressure increases
What occurs during diarrhea?
-ECF volume decreases
-no change in osmolarity of ECF or ICF
-plasma protein concentration and Hct increase
-arterial blood pressure decreases
What occurs during excessive NaCl intake?
-osmolarity of ECF increases
-water shifts from ICF to ECF
-osmolarity of ICF increases
-volume of ECF increases
-volume of ICF decreases
-plasma protein concentration and Hct increase
What occurs when you sweath in the desert?
-ECF volume decreases
-osmolarity of ECF increases
-water shifts from ICF to ECF
-osmolarity of ICF increases
-volume of ECF increases
-volume of ICF decreases
-plasma protein concentration increases
-hematocrit remains unchanged b/c water shifts out of t
What occurs with SIADH?
-excess water is retained
-osmolarity of ECF decreases
-water shifts from ECF to ICF
-osmolarity of ICF decreases
-volume of ECF decreases
-volume of ICF increases
-plasma protein concentration increases
-hematocrit remains unchanged b/c water shifts into
What occurs in adrenocorticol insufficiency?
-excess NaCl is excreted
-osmolarity of ECF decreases
-water shifts from ECF to ICF
-ECF volume decreases
-ICF volume increases
-plasma protein concentration increases
-Hct increases
-arterial blood pressure decreases
What does clearance indicate?
-the volume of plasma cleared of a substance per unit time
What are the units of clearance?
mL/min
Renal blood flow is what percentage of cardiac output?
-25%
List two factors that cause vasoconstriction of renal arterioles.
-sympathetic stimulation
-low concentrations of angiotensin II
Why do low concentrations of angiotensin increase vasoconstriction?
-acts to "protect" GFR
-->vasoconstriction increases GFR
Impact of ACE inhibitors on renal arterioles?
-dilate efferent arterioles
-decrease GFR
-reduce hyperfiltration
List the factors that vasodilate renal arterioles and lead to an increase in RBF?
-prostaglandins E2 and I2
-bradykinin
-NO
-dopamine
How is RBF autoregulated?
-by changing renal vascular resistance
RBF remains constant over what range of arterial pressures?
-80 to 200 mm Hg
How does RBF change with changing arterial pressure?
-if arterial pressure changes, there is a corresponding change to maintain a constant RBF
What are the two methods of autoregulation?
-myogenic mechanism: afferent arterioles contract in response to stretch
-tubuloglomerular feedback: macula dense detects increased delivery of fluid, causes afferent arterioles to contract
What substance is used to measure effective RPF?
-PAH
Why?
-PAH is filtered and secreted
How do you calculate RPF?
-write down equation
How do you measure RBF?
-write down equation
What substance is used to measure effective GFR?
-inulin
Why?
-inulin is filtered, but not reabsorbed or secreted
How do you calculate GFR?
-write down equation
Impact on BUN and serum creatinine when GFR decreases?
-BUN increases
-serum creatinine increases
What happens in prerenal azotemia?
BUN:creatinine ratio increases to > 20:1
Impact of age on GFR?
-GFR decreases with age
What is GFR typically equivalent to?
-about 20%
What happens to the remaining 80%?
-leaves by way of the efferent arterioles and enters the peritubular capillary network
What are the components of the glomerular barrier?
-capillary endothelium
-basement membrane
-filtration slits in the podocytes
What type of molecules typically line the filtration barrier?
-anionic glycoproteins
What occurs to the anionic glycoproteins in kidney disease?
-may lose their charge, leading to proteinuria
Two ways to increase GC hydrostatic pressure?
-dilate afferent arteriole
-constrict efferent arteriole
How can PBS be increased?
-by constriction of the ureters
Why does the glomerular capillary oncotic pressure increase along the length of the capillary?
-because protein concentration increases as plasma is filtered out
How is glucose resorbed from tubular fluid?
-using Na+/glucose co-transporters in the proximal tubule
When do the Na+/glucose carriers become saturated?
-at concentrations greater than 350 mg/dL
At what plasma concentration does glucose first appear in the urine?
-250 mg/dL
Where does secretion of PAH occur?
-from the peritubular capillary blood via carriers in the proximal tubule
Excretion of PAH is the sum of what two values?
-filtered PAH
-secreted PAH
Which substances have the highest clearance?
-those that are both filtered and secreted
What substances have clearances equal to GFR?
-those that are freely filtered, but not resorbed or secreted
What form of acid can "back-diffuse" from urine into blood?
-HA form
At acidic urine pH, what form of acid predominates?
-the HA form
-->therefore at acidic pH, more acid can back-diffuse
What form of base can back-diffuse from the urine to the blood?
-the B form
At alkaline urine pH, what form predominates?
-the B form
-->therefore at alkaline pH, more bas can back-diffuse
What does a TF/P ratio less than 1.0 tell you?
-resorption of the substance has been greater than the resorption of water
What does a TF/P ratio greater than 1.0 tell you?
-resorption of the substance has been less than the resorption of water...or
-there has been secretion of the substance
What is used as a marker for water resorption along the nephron?
TF/P of inulin
Why?
-inulin is freely filtered but not resorbed or secreted
-therefore, its concentration in tubular fluid is indicative of how much water remains
What happens to the TF/P of inulin as water resorption increases?
-increases
True or false: very little sodium is excreted in the urine.
-true
Where is 2/3 of sodium resorbed?
-within the proximal tubule
Is the process isosmotic in the proximal tubule?
-yes, it is
How is Na+ resorbed in the proximal tubule?
-via co-transport with glucose, amino acids, phosphate, and lactate
-via counter-transport with H+
What is the sodium-H+ counter-transport directly linked to?
-resorption of filtered HCO3-
As ECF volume decreases, what happens to proximal tubular resorption?
-resorption increases
Why?
-peritubular capillary volume decreases, therefore capillary hydrostatic forces DECREASE
-peritubular protein concentration increases, therefore capillary oncotic forces INCREASE
As ECF volume increases, what happens to proximal tubule resorption?
-peritubular capillary volume increases, therefore capillary hydrostatic forces INCREASE
-peritubular protein concentration decreases, therefore capillary oncotic forces DECREASE
What percent of filtered sodium is resorbed by the thick ascending limb?
-25%
Mechanism of sodium resorption in the thick ascending limb?
Na+/K+/2Cl- co-transporter
What is notable about this structure?
-site of actin of loop diuretics
List the most important loop diuretic?
-furosemide
The TAL is notably impermeable to...?
-water
Therefore, what is this segment known as?
-the diluting segment
Charge of the lumen in the TAL?
-positive
Why?
-some K+ sneaks back from the cells of the TAL to the lumen
Mechanism of sodium transport in the early distal tubule?
Na+/Cl- co-transporter
This co-transporter is the site of action of...?
-thiazide diuretics
What is this region impermeable to?
-water
What is this region known as?
-the cortical diulating segment
Two cell types of the late distal tubule? Key activities of these cells?
-principal cells: resorb Na+ and water, secreted K+
-alpha-intercalated cells: resorb K+, secrete H+
Impact of aldosterone on the cells of the late distal tubule and collecting duct?
-principal cells: increases Na+ resorption and increases K+ secretion
-alpha-intercalated cells: increases H+ secretion
Impact of ADH on the cells of the late distal tubule and collecting duct?
-principal cells: increases H2O permeability
What does a shift of K+ outside of the cells cause?
-hyperkalemia
What does a shift of K+ into the cells cause?
-hypokalemia
List the locations in the body where potassium is resorbed. Percent contribution?
-proximal tubule: 67%
-thick ascending limb: 20%
Where within the TAL does resorption occur?
-at the Na+/K/Cl- cotransporter
Where within the distal tubule does resorption occur?
-at the H+/K+ ATPase
Resorption within the distal tubule only occurs under what conditions?
-low K+ diet
Where within the distal tubule does K+ secretion occur?
-in the principal cells
List factors that increase K+ secretion by principal cells.
-high dietary K+
-aldosterone
-alkalosis
-thiazide and loop diuretics
-excess anions in the tubule lumen
List factors that decrease K+ secretion by principal cells.
-low dietary K+
-acidosis
-K+ sparing diuretics
Explain why acidosis causes a decrease in K+ secretion.
-H+ pumped into principal cells from blood
-as H+ is pumped into principal cells, K+ is pumped out INTO the blood
-therefore, less K+ can be secreted into the tubule lumen
Explain why alkalosis causes an increase in K+ secretion.
-since there is not enough H+ in the blood, H+ is transferred from principal cells into the blood
-as H+ is pumped OUT of principal cells, K+ is pumped INTO the principal cells
-therefore, more K+ can move down its concentration gradient into the kidney l
Why do thiazide and loop diuretics cause an increase in K+ secretion?
-diuretics increase flow rate through distal tubule
-increased flow rate causes decrease in luminal K+ concentration
-this increases the driving force for K_ secretion
List three K+-sparing diuretics. How do they work?
-spironolactone: antagonist of aldosterone
-triamterene: acts on principal cells
-amiloride: acts on principal cells
Where is most urea resorbed?
-within the proximal tubule
Where can ADH increase urea permeability?
-within the inner medullary collecting ducts only
Relationship with urea excretion and urine flow rate?
-as flow rate increases, urea excretion increases
Where is most phosphate resorbed?
-within the proximal tubule (85%)
By what mechanism?
-cotransport with Na+
Impact of PTH on parathyroid resporption?
-PTH inhibits phosphate resorption by acting on the Na+/phosphate co-transporter
Phosphate is a urinary buffer for...?
-H+
What percent of plasma Ca2+ is filtered across the glomerular capillaries?
-60%
Primary locations for resorption of calcium?
-proximal tubule and thick ascending limb (90%)
-distal tubule and collecting ducts (8%)
Impact of loop diruretics on calcium absorption?
-decrease calcium resorption in the loop of henle
Why?
-because calcium resorption is linked to sodium resorption in the loop of henle
Impact of thiazide diuretics on calcium resorption?
-increase calcium resorption in the distal tubule
Impact of PTH on calcium resorption? How?
-increaess calcium resorption in the distal tubule by activating adenylyl cyclase
In what locations is magnesium resorbed?
-proximal tubule
-thick ascending limb
-distal tubule
In the TAL, what two ions compete for resorption?
-magnesium and calcium
Effect of hypercalcium on magnesium resorption?
-decreases resorption
-increases excretion
Outline the body's response to water deprivation.
decreased water volume --> increased osmolarity --> detected by osmoreceptors in the anterior hypothalamus --> ADH secreted --> ADH increases permeability of distal tubule and CDs to water --> water resorption increases --> urine osmolarity increases, uri
List three circumstances that result in hyperosmotic urine.
-hemorrhage
-water deprivation
-SIADH
What is the corticopapillary osmotic gradient composed of?
-NaCl
-urea
What is it established by?
-countercurrent multiplication
-urea recycling
What is it maintained by?
-countercurrent exchange
Impact of ADH on countercurrent multiplication?
-augmented by ADH
Why?
-because it enhances the activity of the Na+/K+/2Cl-transport
What else does ADH augment?
-urea recycling from the inner medullary collecting ducts
What is free-water clearance used to estimate?
-the ability to concentrate or dilute the urine
What is free water?
-solute-free water
What happens to solute free water in the absence of ADH?
-it is excreted
In the presence of ADH?
-it is resorbed by the late distal tubule
When is CH2O positive?
-when solute-free water is excreted
When is CH2O negative?
-when solute-free water is resorbed
Value of CH2O when urine is isosmotic to plasma?
-CH2O is zero
Value of CH2O when urine is hyposmotic to plasma?
-CH2O is positive
When urine is hyperosmotic to plasma?
-CH2O is negative
Effect of PTH on the kidney?
-decreased phosphate resorption
-increased calcium resorption
Effect of ADH on kidney?
-increases water resorption
Effect of aldosterone on kidney?
-increased sodium and water resorption (principal cells)
-increased potassium secretion (principal cells)
-increased H+ secretion (alpha-intercalated cells)
Effect of ANP on the kidney?
-increased GFR
-decreased sodium resorption
Effect of angiotensin II on the kidney?
-increased Na+/H+ exchange and HCO3- resorption
What are the two types of acid produced in the body? Examples of each?
-volatile acids: CO2
-nonvolatile acids: sulfuric acid, ketoacids, lactic acid, salicylic acid
When are buffers most effective?
-within 1.0 pH unit of the pK of the buffer
What are the two major extracellular buffers?
-HCO3-
-phosphate
What is the most important urinary buffer?
-phosphate
List two intracellular buffers.
-organic phosphates (ATP, ADP, etc)
-proteins (including hemoglobin)
Compare the buffering capacity of deoxyhemoglobin vs. oxyhemoglobin.
-deoxyhemoglobin is a better buffer
How do you calculate pH?
-using the henderson-hasselbalch equation
When the concentrations of A- and HA are equal, what is the pH of the solution equal to?
-the pK of the buffer
In what location is most filtered HCO3- resorbed?
-within the proximal tubule
List factors that cause an increase in HCO3- resorption?
-increase in filtered load
-increase in PCO2
-ECF volume contraction
-angiotensin II
Why does an increase in PCO2 cause an increased rate of HCO3- resorption?
-because the supply of intracellular H+ for secretion is increased
What is this mechanism the basis for?
-renal compensation for respiratory acidosis
Impact of decrease in PCO2 on HCO3- resorption?
-decrease in HCO3- resorption
Why?
-because there is less H+ available for HCO3-
What is this mechanism the basis for?
-renal compensation of respiratory alkalosis
List two methods used to excrete fixed H+.
-NH4
-titratable acid
What does the amount of H+ excreted as titratable acid depend upon?
-amount of urinary buffer present
-pK of the buffer
Minimum urinary pH?
-4.4
What does the amount of H+ excreted as NH4 depend upon?
-amount of NH3 synthesized by renal cells
-urine pH
What is NH3 produced in renal cells from?
-glutamine
Impact of hyperkalemia on NH3 synthesis?
-inhibits NH3 synthesis
Impact of hypokalemia on NH3 synthesis?
-stimulates NH3 synthesis
What does the serum anion gap represent?
-unmeasured anions in serum
What occurs during acute respiratory acidosis/alkalosis?
-renal compensation has not yet occured
What occurs during chronic respiratory acidosis/alkalosis?
-renal compensation has occurred