Exam #3 (Renal) Flashcards
Functions of the Renal System
- Excretory organs
- Regulatory organs (homeostatic fxns) = body vol via filtration, secretion, & reabsorption
- Endocrine organs = secrete 3 hormones (renin, erythropoietin, 1,25-dihydroxycholecalciferol
Peritubular capillaries
surround the nephrons. allow for secretion & reabsorption.
Mannitol is a marker for
ECF b/c it is a large molecule that cannot cross the cell membranes & is therefore excluded from ICF
Isotopic water is a marker for
TBW. will be distributed in ECF & ICF
Evans Blue is a marker for
Plasma. It binds to albumin and cannot pass barrier
The formula for the volume of distribution
Vol. = amount / concentration Vol. = Vol of distribution (L) / Vol of body fluid compartment (L) Amount = Amount of marker injected - Amount excreted (mg) Concentration = Concentration in plasma (mg/L)
Substances used to measure TBW
titrated water, D2O
Substances used to measure ECF
Sulfate, inulin, mannitol
Substances used to measure plasma
Radio-iodinated serum albumin (RISA), Evans blue
How to measure Interstitial compartment
not measured directly. ECF - plasma
How to measure ICF
not measured directly. TBW - ECF
What happens to the ICF & ECF compartments as a result of diarrhea?
Loss of isotonic fluid aka isosmotic volume contraction. No change in osmolarity, no water shift, ECF volume decreases & ICF volume remains the same.
What happens to the ICF & ECF compartments when a person is deprived of water?
You sweat, sweat is hyposmotic (more water than salt to it), ECF volume decreases & ECF osmolarity increases, water shifts from ICF to ECF, results are ECF & ICF volumes both decrease
What happens to the ICF & ECF compartments within a person with adrenal insufficiency?
Hyposmotic volume contraction. A person w/ adrenal insufficiency has a deficiency of several hormones including aldosterone, a hormone that normally promotes Na+ reabsorption in the distal tubule & collecting ducts. Excess NaCl is excreted in urine; NaCl is an ECF solute so ECF osmolarity decreases. ECF osmolarity is now less than ICF osmolarity, causing water to shift from ECF to ICF. Results: ECF volume will be decreased & ICF volume will be increased.
What happens to the ICF & ECF compartments when a person has an infusion of isotonic NaCl?
The opposite of someone w/ diarrhea. All the isotonic NaCl solution is added to the ECF, causing an increase in ECF volume but no change in ECF osmolarity. There will be no shift of water between ICF & ECF b/c there is no difference in osmolarity between the 2 compartments. Aka isosmotic volume expansion
What happens to the ICF & ECF compartments when a person has excessive NaCl?
Ingesting dry NaCl (eg: bag of potato chips) will increase the total amount of solute in the ECF, so ECF osmolarity increases. ECF osmolarity is higher than ICF osmolarity. Water shifts from ICF to ECF. Decreases ICF volume & increasing ECF volume. Result: b/c of the shift of water out of the cells, ICF volume will decrease & ECF volume will increase. Aka hyperosmotic volume expansion
What happens to the ICF & ECF compartments in a person w/ SIADH (syndrome of inappropriate antidiuretic hormone)?
Aka hyposmotic volume expansion. A person w/ SIADH secretes inappropriately high levels of ADH, which promotes water reabsorption in the collecting ducts. When ADH levels are abnormally high, too much water is reabsorbed & the excess water is retained & distributed throughout the total body water. The volume of water that is added to ECF & ICF is in direct proportion to their original volumes. When compared w/ the normal state, ECF & ICF volumes will be increased and ECF & ICF osmolarities will both decrease.
What is Renal Clearance?
The volume of plasma completely cleared of a substance by the kidneys per unit time
What is the Renal Clearance formula?
C = ([U]xV)/[P]
C = Clearance (mL/min) [U]x = Urine concentration of substance x (mg/mL) V = Urine flow rate per minute (mL/min) [P]x = Plasma concentration of substance x (mg/mL)
Renal clearance of Albumin
Approximately zero. Not filtered across the glomerular capillaries
Renal clearance of Glucose
Approximately zero. It is filtered & then completely reabsorbed.
Renal clearance of Na+, urea, phosphate, & Cl-
Higher than zero. Filtered & then partially reabsorbed
Renal clearance of Inulin
Freely filtered. Neither reabsorbed nor secreted, so its clearance measures the glomerular filtration rate
Renal clearance of Para-aminohippuric acid (PAH)
Have the highest clearances of all substances. Both filtered & secreted.
Only substance whose clearance is exactly equal to the glomerular filtration rate (GFR)
Inulin
Unique properties of Inulin
Only substance whose clearance is exactly equal to the glomerular filtration rate (GFR)
Freely filtered, neither reabsorbed nor secreted. Thus, the amount of inulin filtered will be exactly equal to the amount of inulin excreted.
Is a reference substance called a glomerular marker
What is the clearance ratio?
The clearance of any substance (x) compared w/ the clearance of inulin
Cx/Cinulin
If the Clearance ratio (Cx/Cinulin) = 1 that means
The clearance of “X” equals the clearance of inulin. The substance also must be a glomerular marker (filtered, but neither reabsorbed nor secreted)
If the Clearance ratio (Cx/Cinulin) is less than 1 that means
The clearance of “X” is lower than the clearance of inulin. Either the substance is not filtered, or it is filtered & subsequently reabsorbed.
Can be Na+, Cl-, HCO3-, phosphate, urea, glucose, & amino acids
If the Clearance ratio (Cx/Cinulin) is greater than 1 that means
The clearance of “X” is higher than the clearance of inulin. The substance is filtered & secreted.
Can be organic acids (PAH), bases and, under some conditions, K+
Renal Blood Flow is what % of Cardiac Output?
25%
Renal Blood Flow is directly proportional to ___ & inversely proportional to ____
RBF is directly proportional to the pressure gradient between the renal artery & the renal vein, and it is inversely proportional to the resistance of the renal vasculature
Regulation of Renal Blood Flow
- Sympathetic nervous system & circulating catecholamines via alpha 1 receptors which are numerous in the afferent arterioles -> vasoconstrict -> decrease in both RBF & GFR
- Angiotensin II -> vasoconstrictor of both afferent & efferent arterioles. It increases resistance, and decreases blood flow.
- Prostaglandins -> vasodilation of both afferent & efferent arterioles, they modulate vasoconstriction.
- Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) -> inhibit synthesis of prostaglandins in the kidneys, interfere w/ the protective effects of prostaglandins on renal function following a hemorrhage
Renal Blood Flow maintains constant over the range of arterial blood pressure from
80 - 200 mmHg
Autoregulation of RBF is accomplished by
Changing renal vascular resistance to maintain blood flow
Ultrafiltrate
Fluid that is filtered, is similar to interstitial fluid
Contains water & all of the small solutes of blood, but it does not contain proteins & blood cells
Starling Equation
GFR = Kf [(Pgc - Pbs) - πgc]
GFR = Glomerular filtration rate (mL/min) Kf = Hydraulic conductance or Filtration coefficient (mL/min•mmHg) Pgc = Hydrostatic pressure in glomerular capillary (mmHg) Pbs = Hydrostatic pressure in Bowman's space (mmHg) πgc = Oncotic pressure in glomerular capillary (mmHg)
In the Starling Equation, Net ultrafiltration pressure
Always favors filtration. Sum of pressures
Effect of the constriction of afferent arteriole on RPF & GFR
RPF decreases
GFR decreases
Effect of the constriction of efferent arteriole on RPF & GFR
RPF decreases
GFR increases
Effect of an increased plasma protein concentration on RPF & GFR
RPF no change
GFR decreases
Effect of a decreased plasma protein concentration on RPF & GFR
RPF no change
GFR increases
Calculation of GFR
The clearance of inulin equals the GFR
GFR = ([U]inulin x V) / [P]inulin = Cinulin
GFR = Glomerular filtration rate (mL/min) [U]inulin = Urine concentration of inulin (mg/mL) [P]inulin = Plasma concentration of inulin (mg/mL) V = urine flow rate (mL/min) Cinulin = Clearance of inulin (mL/min)
What is the filtration fraction?
The fraction of the RPF that is filtered across the glomerular capillaries
Filtration fraction = GFR/RPF
The filtration fraction is normally
About 0.20, or 20%
20% of the RPF is filtered
80% is not filtered
We filter about 180L/day
The Glucose Titration Curve
Depicts the relationship between plasma glucose concentration & glucose reabsorption. At plasma glucose concentration of < 250 mg/dL, all filtered glucose is reabsorbed & excretion is zero. At plasma glucose concentration of > 350 mg/dL, the carriers are saturated & Tm is reached, so increasing plasma concentration above 350 mg/dL will not increase the rate of reabsorption. Threshold = the plasma concentration at which glucose 1st appears in urine; ~250 mg/dL
The Splay region of the Glucose Titration Curve
Region between threshold & Tm (btw 250 & 350)
Represents excretion of glucose before Tm is reached
What is glucosuria?
Glucose in urine. Found in uncontrolled Diabetes Mellitus. Found during pregnancy, GFR is increased, thus reaching Tm hence, glucose in urine.
Congenital abnormalities of the Na+-glucose cotransporter are associated w/ decreases in Tm, hence glucose in urine
90% of PAH is
bound to proteins
What is PAH?
An organic acid used to measure RPF
Secretion of PAH
- Has transporters in proximal tubule
- Has similar characteristics as that of glucose for Tm
- When Tm is reached, no more PAH can be secreted & excretion rate decreases. Hence RPF is measured at low [P]pah
Excretion of PAH
- Excretion is the sum of filtration & secretion
- Initially excretion is a faster rate b/c both filtration & secretion is active
- Later, excretion rate slows down due to Tm
Substances w/ the highest clearance
PAH, Urea. Due to filtration + secretion
Substance w/ the lowest clearance
Na+, Ca2+, PO4-
Due to no filtration or filtration followed by reabsorption
With respect to the renal excretion of weak acids and bases, the relevant points are
(1) the relative amounts of the charged and uncharged species depend on urine pH, and (2) only the uncharged (i.e., “non-ionic”) species can diffuse across the cells.
At acidic urine pH, ___ predominates, there is more “back-diffusion” from urine into blood, and the excretion (and clearance) of salicylate is decreased. At alkaline urine pH, ___ predominates, there is less “back-diffusion” from urine to blood, and the excretion (and clearance) of salicylate is increased.
HA
A-
Clearance of a weak acid is highest at _____ urine pH & lowest at _____ urine pH
Clearance of a weak acid is highest at alkaline urine pH and lowest at acidic urine pH
[TF/P]x Ratio
Compares the concentration of a substance in tubular fluid to its concentration in systemic plasma. B/c plasma concentration is constant, changes in ratio would be reflective of tubular fluid.
A [TF/P]x Ratio of 1 means
There has been no reabsorption of substance or reabsorption of substance is the same as reabsorption of water
A [TF/P]x Ratio less than 1 means
Reabsorption of substance > reabsorption of water, and the concentration in tubular fluid is less than that in plasma.
Eg: If [TF/P]na = 0.8 then the [Na+] in TF is 80% of the [Na+] in plasma
A [TF/P]x Ratio more than 1 means
Reabsorption of substance < reabsorption of water or there has been secretion of the substance
Na+ balance means
Na+ excretion exactly equals Na+ intake
Eg: a person who ingests 150 mEq of Na+ daily must excrete exactly 150 mEq of Na+ daily
Na+ is freely filtered across the glomerular capillary. Therefore TF of bowman’s space = plasma ([TF/P]na = 1)
Only 1% of Na+ is excreted
A positive Na+ balance means
Na+ excretion is less than Na+ intake
ECF volume expansion
Increase in blood volume & arterial pressure
Edema due to increase hydrostatic pressure
A negative Na+ balance means
Na+ excretion is greater than Na+ intake
ECF volume contraction
Decrease in blood volume & arterial pressure
The site of Glomerularotubular Balance is
Proximal Convoluted Tubule
Difference between Na+ content & Na+ concentration
Na+ concentration is determined by both Na+ content & water
The Proximal Tubule
Reabsorbs 2/3 or 67% of filtered Na+ & H2O
Site of glomerulotubular balance
Process is isosmotic: Na+ & H2O are reabsorbed proportionally, therefore TF/P = 1
Middle & Late Proximal Tubule
Na+ is reabsorbed w/ Cl- via cotransport
Filtered glucose, amino acids, & HCO3- have already been completely removed from the TF by reabsorption in the early proximal tubule.
Loop of Henle Consists of what parts of the nephron & is permeable to what?
Thin Descending Limb
Thin Ascending Limb
High permeability to small solutes & water
Descending Limb of the Loop of Henle
- Permeable to water & small solutes such as NaCl & urea
- Water moves out of the thin descending limb, solutes move into the thin descending limb, & TF (Tubular Fluid) becomes progressively hyperosmotic
Thin Ascending Limb of the Loop of Henle
- Permeable to NaCl, but it is impermeable to water
- Solute moves out of the thin ascending limb w/o water, & the tubular fluid becomes progressively hyposmotic
Thick Ascending Limb of the Loop of Henle
Aka the diluting segment
Reabsorbs 25% of filtered Na+
Contains Na+-K+-2Cl- cotransporter in the luminal membrane
Point of action of loop diuretics
Impermeable to water; NaCl is reabsorbed w/o water. [TF/P]na & [TF/P]osmolarity is less than 1
The Thick Ascending Limb of the Loop of Henle contains what transporters in the luminal membrane?
Contains Na+ - K+ - 2Cl- cotransporter in the luminal membrane
The point of action of loop diuretics is in
The Thick Ascending Limb of Loop of Henle
How do loop diuretics work in the Loop of Henle?
Furosemide, Ethracrynic acid, Butamide
Inhibit the Na+ - K+ - 2Cl- cotransporter by binding the Cl-, thus 25% of Na+ can be excreted
Early Distal Tubule
Called the cortical diluting segments. Impermeable to water
Reabsorbs NaCl by a Na+ - Cl- cotransporter which is the site of action of thiazide diuretics
Site of action of thiazide diuretics
On the Na+ - Cl- cotransporter in the Early distal tubule
Principal Cells in the Late Distal Tubule & Collecting Duct
Reabsorbs Na+ & Water
Secrete K+
Aldosterone increases Na+ reabsorption & K+ secretion. Hypokalemia w/ increased aldosterone b/c it is located in the cortex
ADH increases water permeability by directing the insertion of water channels in the luminal membrane
Alpha-Intercalated Cells in the Late Distal Tubule & Collecting Duct
Secrete H+ by a H+ - adenosine triphosphatase (ATPase)
Reabsorbs K+ by a H+,K+ - ATPase
Aldosterone increases H+ secretion by stimulating H+ ATPase
Effective Arterial Blood Volume (EABV)
Portion of the ECF volume contained in the arteries
Changes in ECF volume lead to changes in EABV in the same direction
Mechanisms for Regulation of Na+ Balance
- Sympathetic nerve activity: decrease in arterial pressure -> activation of baroreceptors -> vasoconstriction & increase proximal tubule Na+ reabsorption
- Atriopeptin (ANP): secreted by right atrium
- Urodilation: secreted by the kidney
- Brain Natriuretic Peptide (BNP): secreted by cardiac atrial cells & brain
The latter 3 increase ECF -> vasodilation of afferent arterioles, vasoconstriction of efferent arterioles -> increase GFR & decrease Na+ reabsorption in the late distal tubule & collecting ducts
The bodies response to increased Na+ intake via sympathetic activity
increased Na+ intake => increased ECF & EABV => decreased sympathetic activity => dilation of afferent arterioles (increasing GFR) & decreasing Na+ reabsorption in proximal tubule => increased Na+ excretion
The bodies response to increased Na+ intake via ANP (Atriopeptin)
increased Na+ intake => increased ECF & EABV => increase ANP => constriction of efferent arterioles (increasing GFR) & decrease Na+ reabsorption in the collecting ducts => increased Na+ excretion
The bodies response to increased Na+ intake via peritubular capillary oncotic pressure
increased Na+ intake => increased ECF & EABV => decrease peritubular capillary oncotic pressure => decreased Na+ reabsorption in the proximal tubule => increased Na+ excretion
The bodies response to increased Na+ intake via Renin-Angiotensin-Aldosterone complex
increased Na+ intake => increased ECF & EABV => decrease Renin-Angiotensin-Aldosterone complex => decreased Na+ reabsorption in the proximal tubule & collecting ducts => increased Na+ excretion
The bodies response to decreased Na+ intake via sympathetic activity
decreased Na+ intake => decreased ECF & EABV => increase sympathetic activity => constriction of afferent arterioles (decreasing GFR) & increasing Na+ reabsorption in the proximal tubule => decreased Na+ excretion
The bodies response to decreased Na+ intake via ANP (Atripeptin)
decreased Na+ intake => decreased ECF & EABV => decrease ANP => dilation of efferent arterioles (decreasing GFR) & increasing Na+ reabsorption in the collecting ducts => decreased Na+ excretion
The bodies response to decreased Na+ intake via peritubular capillary oncotic pressure
decreased Na+ intake =>
decreased ECF & EABV =>
increase peritubular capillary oncotic pressure =>
increase Na+ reabsorption in the proximal tubule =>
decreased Na+ excretion
The bodies response to decreased Na+ intake via renin-angiotensin-aldosterone system
decreased Na+ intake =>
decreased ECF & EABV =>
increase renin-angiotensin-aldosterone =>
increase Na+ reabsorption in the proximal tubule & collecting ducts =>
decreased Na+ excretion
The majority of K+ is found in the ICF or ECF?
ICF
In Hyperkalemia
shift of K+ out of cell
In Hypokalemia
shift of K+ into the cell
Internal K+ balance & External K+ balance
Internal = distribution of K+ across cell membranes
External = on a daily basis, urinary excretion of K+ must be capable of varying from 50 to 150 mEq/day
When urinary excretion of K+ exactly equals intake of K+ in the diet
K+ balance
Causes of K+ shift out of cells - Hyperkalemia
Insulin deficiency Beta2-Adrenergic antagonists Alpha-Adrenergic agonists Acidosis Hyperosmolarity (into ECF) Cell lysis Exercise
Causes of K+ shit into cells - Hypokalemia
Insulin Beta2-Adrenergic agonists Alpha-Adrenergic antagonists Alkalosis Hyposmolarity (into ICF)
Reabsorption of K+ in the Glomerular capillaries
Filtration occurs freely across the glomerular capillaries. Therefore TF/Pk in Bowman’s space = 1
Reabsorption of K+ in the Proximal tubule
Reabsorbs 67% of K+ along w/ Na+ & H2O
Reabsorption of K+ in the Thick Ascending Limb of Loop of Henle
Reabsorbs 20%
Reabsorption involves the Na+ - K+ - 2Cl- cotransporter
Reabsorption of K+ in the Distal tubule & Collecting duct
Involves a H+,K+ - ATPase in the alpha-intercalated cells
Occurs only on a low K diet
Secretion of K+ is via principal cells or alpha-intercalated cells?
Principal cells
Causes of Increased K+ Secretion
High K+ diet Hyperaldosteronism Alkalosis Thiazide diuretics Loop diuretics Luminal anions
Causes of Decreased K+ Secretion
Low K+ diet
Hypoaldosteronism
Acidosis
K+ - sparring diuretics
Spironolactone, triamterne, amiloride all
inhibit actions of aldosterone on principal cells
Urea in Renal Reabsorption
50% of filtered urea is reabsorbed passively in proximal tubule
Other part of nephron is impermeable to urea
ADH increases urea permeability in the inner medullary collecting ducts
The body uses a waste like urea in order to reabsorb water
Phosphate in Renal Reabsorption
85% of the filtered phosphate is reabsorbed in the proximal tubule by Na+ - phosphate cotransport
Rest of the nephron is impermeable to phosphate; 15% is excreted
PTH inhibits phosphate reabsorption by inhibiting Na+ - Phosphate cotransport proximal tubule
Also when couple w/ Gs proteins, adenylyl cyclase is activated which in turn increase cAMP that is excreted in urine.
Ca2+ in Renal Reabsorption
60% is filtered
Proximal tubule & thick ascending limb reabsorbs over 90% of filtered
Loop diuretics increase Ca2+ excretion
Distal tubule & collecting duct reabsorbs 8%
PTH increases Ca2+ reabsorption
Thiazides increases reabsorption
Mg2+ in Renal Reabsorption
Reabsorbed in proximal tubule, thick ascending limb, distal tubule
Mg2+ & Ca2+ competes for reabsorption in the thick limb. Hypercalcemia -> increased Mg2+ excretion (by inhibiting Mg2+ reabsorption)
Hypermagnesia -> increased Ca2+ excretion (by inhibiting Ca2+ reabsorption)
Renal Response to Water Deprivation
Deprive of H2O -> Increased Plasma Osmolarity -> Stimulates osmoreceptors in anterior hypothalamus -> increase ADH secretion from posterior pituitary -> increase H2O permeability of principal cells (from late distal tubule & collecting duct) -> increase H2O reabsorption -> increase urine osmolarity & decrease urine volume => decreases plasma osmolarity toward normal
Also the osmoreceptors in the anterior hypothalamus increase thirst and have you drink H2O
Renal Response to Water Intake
Drink H2O -> Decreased Plasma Osmolarity -> inhbits osmoreceptors in anterior hypothalamus -> decrease ADH secretion from posterior pituitary -> decrease H2O permeability of principal cells in late distal tubule & collecting duct -> decrease H2O reabsorption -> decrease urine osmolarity & increase urine volume => Increases plasma osmolarity toward normal
Also the osmoreceptors in the anterior hypothalamus decrease thirst & less drinking H2O
Production of Concentrated/Hyperosmotic Urine
Urine osmolarity > Plasma osmolarity
Due to high ADH levels
Mechanisms: Corticopapillary osmotic gradient – high ADH
Effect of ADH on nephron
Everything stays the same except
At late distal tubule: ADH increase water permeability of principal cells. Water is reabsorbed until distal tubule osmolarity = surround IF in renal cortex. TF/Posm = 1
At collecting ducts: ADH increases water permeability of principal cells, 1200 mOsm/L. TF/Posm = > 1
Production of Dilute/Hyposmotic urine
Urine osmolarity < plasma osmolarity
Produced by low levels of ADH (central diabetes insipidus or water drinking) or ineffective ADH (nephrogenic diabetes insipidus)
Mechanisms: Corticopapillary osmotic gradient is smaller
Effect of Decreased Corticopapillary Osmotic Gradient
Thick ascending limb: Na, K, & Cl are reabsorbed but water is impermeable, hence dilution. TF/Posm =< 1
Early distal tubule: Further dilution b/c of impermeability to water while NaCl is reabsorbed. TF/Posm =< 1
Late distal tubule & collecting duct: Due to absence of ADH, no permeability to water, hence dilution (75mOsm/L). TF/Posm =< 1
Free Water Clearance
Used to estimate the ability to concentrate or dilute urine
Produced in the diluting segments of the kidney; (thick ascending limb & early distal tubule) where NaCl is reabsorbed leaving water behind
In the absence of ADH Free Water Clearance is
Positive
Urine is hyposmotic
Solute free
Occurs w/ excessive water intake, central/nephrogenic diabetes insipidus
A positive Free Water Clearance occurs w/
Occurs w/ excessive water intake, central/nephrogenic diabetes insipidus.
When ADH is present Free Water Clearance is
Negative
Urine is hyperosmotic
Occurs in water deprivation or SIADH
When Free Water Clearance is zero
When no solute-free water is excreted
Urine is isosmotic w/ plasma (called isosthenuric)
Unusual, but can occur during treatment w/ loop diuretic where NaCl reabsorption is inhibited
