Renal Physiology Flashcards
1
Q
Effect of sympathetics on renal function
A
- Decrease in RPF
- Decrease in GFR
- Decrease in pressure of peritubular capillary
- Increase in oncotic pressure in peritubular capillary
2
Q
Filtered Load
A
FL = GFR * Px
3
Q
Excreted Load
A
EL = Vu*Ux
4
Q
Fractional Excretion
A
Fraction of filtered load of a solute that is excreted.
FE = EL/FL = (Vu*Ux) / (GFR*Px) = Cx/Ccr
If < 1 reabsorbed
If > 1 secreted
5
Q
Fractional Filtration
A
FF = GFR/RPF
Normally about 20%
6
Q
Renal Blood Flow (RBF)
A
RBF = RPF/(1-hematocrit)
Normally about 1000 ml/min or about 20% of Cardiac Output
7
Q
ADH
A
Primary determinant of plasma osmolality through the control of water reabsorption or excretion in the distal nephron
- Increases permeability of CCD and MCD to water
- Increases permability of MCD to urea
- Stimulates the Na-K-2Cl pump in the thick ascending limb of the LOH
- Stimulates production of renal prostaglandins
8
Q
Renin-Angiotensin II System
A
Primary “Low Blood Volume (low pressure) Response System”
- Causes vasoconstriction of both efferent and afferent arterioles that limits the fall in GFR relative to RBF in low volume states
- Stimulates aldosterone release
- Stimulates synthesis of vasodilatory prostaglandins
- Inhibits renin release
- Increases sodium and water reabsorption in the proximal tubule
9
Q
Aldosterone
A
- Increases Na+ and Cl- reabsorption in the CCD and MCD
- Increases isoosmotic reabsorption of water
- Increases K+ and H+ secretion in the collecting ducts
- Primary determinant of urinary K+ excretion (balance of reabsorption and secretion)
10
Q
Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP)
A
Part of low pressure, high blood volume response system
- Causes renal vasodilation and increases both RBF and GFR
- Increase Na+ excretion (natriuresis) and water excretion (diuresis)
11
Q
Urodilatin
A
ANP-like hormone produced within the nephron in response to hypervolemia
- Increases Na+ excretion (natriuresis) and water excretion (diuresis)
12
Q
Prostaglandins
A
PGE2 and prostacyclin are vasodilators that modulate RBF by antagonizing the vasoconstrictor effects of sympatheics and angiotensin II
13
Q
Parathyroid Hormone
A
Released in response to low plasma Ca2+ concentration
- Activates calcitriol
- Increases active reabsorption of Ca2+ in the distal tubule
- Decreases proximal tubule reabsorption of phosphate (i.e., increases phosphate excretion)
14
Q
Calcitriol
A
Most active form of Vitamin D
- Increases Ca2+ and Phosphate reabsorption
- Negative feedback on PTH release
15
Q
Catecholamines
A
NE and EPI
- Vasoconstricts afferent and efferent arterioles (alpha-1)
- Decreases RBF and GFR
- Stimulates Na+ reabsorption in proximal tubule and LOH
- Activates renin-angiotensin system via ß1 receptors in JGA of afferent arteriole
16
Q
Kinins
A
Vasodilators that appear to antagonize neurohumoral vasoconstriction similar to the prostaglandins
- May have role in Na+ and water handling in the collecting duct by antagonizing ADH-mediated water reabsorption
17
Q
How does afferent arteriole constriciton change renal function?
A
Decreases GFR and RPF
18
Q
How does efferent arteriole constriction change renal function?
A
Increases oncotic pressure and and decreases hydrostatic pressure
Increases GFR
Decreases RPF
Increases FF (GFR/RPF)
19
Q
How does an increase in plasma protein concentration change renal function?
A
Decreases GFR, which decreases the FF
20
Q
How does a decrease in plasma protein concentration change renal function?
A
Increases GFR, which increases FF (GFR/RPF)
21
Q
What is responsible for most of renal oxygen consumption?
A
NaK-ATPase Pump
Which is responsible for the active reabsorption of Na+
22
Q
How are the glomerular and peritubular capillaries arranged? Why is this important?
A
They are arranged in series.
This allows solutes and fluids filtered at the glomerulus and reabsorbed in the tubules to be reabsorbed by peritubular capillaries and returned to systemic circulation.
23
Q
What is the balance of Starling forces in glomerular capillaries?
A
Capillary Pressure > Oncotic Pressure
Always results in filtration
24
Q
What is the balance of Starling forces in peritubular capillaries?
A
Oncotic Pressure > Hydrostatic Pressure
Always results in reabsorption
25
What is the importance of autoregulation of RBF and GFR?
What accompanies this autoregulation as arterial pressure increases?
It uncouples renal function from changes in arterial pressure and ensures maintenance of renal function.
**Pressure diuresis** occurs when arterial pressure is increased meaning urine output is increased as a compensatory mechanism to maintain normal blood pressure
26
What are the mechanisms of autoregulation of GFR and RBF?
1. Myogenic Vasoconstriction
1. Occurs in afferent arterioles in response to sudden increases in renal perfusion pressure
2. This stretches the arteriole causing vasoconstriction which reduces flow and hydrostatic pressure in glomerular capillaries
1. Autoregulation of GFR is secondary to autoregulation of RBF
2. Tubuloglomerular Feedback
1. Macula densa provides feedback regarding flow and solute delivery (Cl-) to the afferent arteriole
2. If GFR too high and increased flow, then the afferent arteriole vasoconstricts leading to a decrease in RBF and GFR
3. If GFR and flow too low → vasodilation of afferent arteriole leads to increased RBF and GFR
1. This also results in an increase in renin release via prostaglandin PGE2 and NO
27
What can override the autoregulatory mechanisms?
* Extrinsic Control
* Neural and Humoral Control
28
How does neural control affect RBF and GFR?
1. Afferent and Efferent Arterioles are innvervated by sympathetic nerve fibers
2. Low level stimulation constricts both afferent and efferent arterioles resulting in less of a decrease in GFR and RBF
3. Greater stimulation causes parallel reductions in GFR and RBF
4. Appears to be solely related to maintenance of arterial pressure and not the preservation of renal function (intrinsic control)
29
How does humoral control affect RBF and GFR?
Hormones and endogenous substances produce either renal vasoconstriction or vasodilation
* Renal Vasoconstrictors
* Angiotensin II
* Catecholamines
* ADH
* Modulate/Antagonize Constrictor Effects
* Prostaglandins
* Kinins
* Renal Vasodilation
* ANP
* Urodilatin
30
What is the limiting element of the glomerular filtration barrier?
Basement Membrane
31
What are the principal determinants of glomerular barrier permeability?
* Size and number of pores in glomerular barrier
* Presence of fixed negative charges in barrier (mainly basement membrane)
* Negatively charged glycoproteins retard the movement of negatively charged macromolecules like plasma proteins
* Nephrotic Syndrome results in a loss of these fixed negative charges
32
What is back-leak and how does it occur?
Back-leak is the bulk flow of water and solutes into the proximal tubule
* Occurs with afferent and efferent arteriolar vasodilation in hypervolemic states that leads to a decreased filtration fraction (GFR/RPF)
* Balance of Starling forces in peritubular capillaries become less favorabe for reabsorption, so water and solutes reabsorbed in the proximal tubule are not readily taken up into the peritubular capillaries → leads to a progressive rise in interstitial hydrostatic pressure
33
Hypovolemia Effects
**Decreased GFR and RBF**
* Arterial pressure falls
* Decreased PG and RBF
* Leading to decreased baroreceptor activity and a reflex increase in sympathetic discharge causing vasoconstriction
* Decreased PG and RBF (PG reduction less than RBF)
* Constriction of Afferent decreases PG and RBF
* Constriction of Efferent increases PG and decreases RBF
* Also occurs with increased renin release and increased circulating levels of angiotensin II
* Increased concentration of plasma proteins → increases oncotic pressure in systemic capillaries → decreases GFR
* Decreased Kf
* Mesangial contraction → reducing glomerular perfusion, decreasing surface area for filtration
* Podocytes may also contract and reduce the size of slit pores
* Efferent vasoconstriction → filtration equilibrium being reached sooner along length of glomerular capillaries
34
Hypervolemia Effects
**Increased GFR and RBF**
* Increased baroreceptor activity, which decreases sympathetic discharge to resistance vessels (limited degree of vasodilation)
* Increase in blood volume causes stretching of atria → releases ANP from atrial myocytes → ANP and urodilatin vasodilate _increase GFR and RBF_ and _increase Na+ excretion_
* Intrarenal baroreceptors respond to stretch by decreasing renin release that lowers angiotensin II levels
* Increase in prostaglandins
* Increased mean arterial pressure causes small increases in PG and RBF
* Afferent and Efferent arteriole dilation → Increases RBF and PG
* Afferent dilation → Increases RBF and PG
* Efferent dilation → Decreases PG and Increases RBF
* Dilution of plasma proteins → decreased oncotic pressure in systemic capillaries
* Increase Kf
* Relaxation of mesangial cells
* Filtration equilibrium reached further along the length of the glomerular → greater capillary surface area is utilized for filtration
35
Clearance Equation
Cx = (Vu \* Ux) / Px
36
What solutes can be used to estimate GFR?
Inulin
Creatinine
37
Renal Plasma Flow (RPF)
Clearance of PAH, which is avidly secreted by tubules, is used to estimate RPF
CPAH = RPF = (Vu * UPAH) / PPAH
\*Averages 625 ml/min\*
38
Fraction Reabsorption
FR = 1 - FE
39
Fraction Excretion of H2O
FEH2O = Vu / GFR = PCR / UCR
40
Function of the Glomerulus
* Creates ultrafiltrate of plasma
* Controls GFR
* Activation of Renin-Angiotensin-Aldosterone System (RAAS)
41
Proximal Tubule Function
* Isosmotic reabsorption of about 65% of filtered load of Na+, Cl-, and H2O
* Reabsorbs almost all filtered glucose and amino acids
* Reabsorbs most of filtered K+, HCO3-, Ca2+, Mg2+, and phosphate
* Secretes H+, NH3, and organic acids and bases (Some K+)
* Relatively leaky junctions allow diffusion of solutes via paracellular route
* Fluid leaving is isotonic to plasma
42
Loop of Henle Function
* Reabsorbs about 20% of the filtered load of Na+ and water
* _T__hin descending limb_ permeable to water
* Larger amount of solute is reabsorbed in ascending limb → net solute reabsorption in loop is greater than water reabsorption
* Fluid leaving is hypotonic to plasma
* _Thin Ascending Limb_
* __Impermeable to water
* Permeable to Na and Cl
* Contains a urea transporter (moves urea into tubule down concentration gradient)
* _Thick Ascending Limb_ is impermeable to water (diluting segment)
* Allows for formation of steep osmotic gradient b/t tubule and interstitium - countercurrent multiplier
* Na+, K+, and Cl- actively reabsorbed in thick ascending limb (**Na-K-2Cl co-transporter**) → hypertonic interstitium
* Increases driving force for water reabsorption from thin descending limb and medullary collecting ducts
* Excess Na+ and Cl- are removed from the medullary interstitium by vasa recta
43
Distal Nephron Function
* Fine tunes urine volume and solute concentration as 85% of water and solutes are already absorbed
* Consists of:
* Distal Tubule
* Cortical Collecting Tubules
* Medullary Collecting Ducts
44
Distal Tubule Function
* Reabsorbs small fraction of filtered Na+ and Cl-
* Site of active control of Ca2+ reabsorption and excretion
45
Cortical Collecting Tubules Function
* Principal Cells
* Reabsorb Na+ and Cl-
* Secrete K+ (_aldosterone sensitive_)
* Intercalated Cells
* Secrete H+
* Reabsorbe K+
* Secrete HCO3- in metabolic alkalosis
* Reabsorb water in presence of ADH
46
Medullary Collecting Ducts Function
* Reabsorbs Na+ and Cl- (_aldosterone sensitive_)
* Inhibit tubular reabsorption of Na+ (_ANP and BNP sensitive_)
* Water and Urea reabsorption (dependent on ADH levels)
* Secrete H+ and NH3
* Can either reabsorb or secrete K+
47
Where does reabsorption of glucose occur?
Proximal Tubule Only
48
Where are organic solutes (glucose, amino acids, etc.) reabsorbed?
Proximal Tubule
49
How is most glucose reabsorbed?
Na+-Glucose Symporter driven by NaK-ATPase Pump
50
What is the energy source driving the Na-Glucose symporter?
The electrochemical gradient for Na+ generated by NaK-ATPase Pump
51
On the basolateral membrane, how does glucose exit the tubular cells?
GLUT uniporter
52
Fanconi Syndrome
Impaired proximal tubular reabsorption
53
Cystinuria
Defective cystine reabsorption; stone formation
54
Substances that exhibit tubular maxima and renal thresholds
1. Glucose
2. Amino Acids
3. Phosphate
4. Uric Acid
5. Ketone Bodies
6. Vitamins
55
What form of a weak acid or base is lipid soluble?
Nonionized Form
Can passively diffuse across the epithelium down the prevailing concentration gradient
56
What form of a weak acid or base is not lipid soluble and becomes diffusion trapped?
Ionized form
57
Alkalinizing the urine will enhance secretion and excretion of what?
Weak Acids
58
Acidizing the urine enhances the secretion and excretion?
Weak Bases
59
What volume state will enhance tubular solute and water reabsorption?
Hypovolemic
60
What volume state will reduce reabsorption of weak acids and bases?
Hypervolemic
61
What are the sites of Na+ reabsorption?
1. Proximal Tubule (65%)
2. Loop of Henle (20%)
3. Distal Tubule (5-10%)
4. Collecting Tubules and Ducts (About 5%)
62
What is glomerulotubular balance?
It is a load-dependent phenomenon due to changes in filtered load of glucose, phosphate, amino acids, bicarbonate etc that influence Na reabsorption and to relative changes in Pc and oncotic pressure in the peritubular capillaries that reflect changes in GFR and influence the reabsorptive potential
63
What percentage of the filtered load of Na is normally excreted?
0.6%
64
At steady state, what equals the daily intake of Na?
Daily Urinary Excretion of Na
65
What percentage of total renal energy is expended by NaK-ATPase Pump?
90%
66
What is the most abundant anion in glomerular filtrate?
Cl-
67
Unidirectional Na Transport
Na passively enter the proximal tubular cells through Na channels down its electrochemical gradient accompanied by Cl
Na is then actively extruded across basolateral surfaces by NaK-ATPase pump
68
Na-H Exchange
Secondary active transport, Na reabsorption into proximal tubular cells is coupled w/ secretion of H into tubular lumen
Accounts for large fraction of total Na reabsorption in the proximal tubule and is coupled with the reabsorption of HCO3- and Cl-
Is stimulated by angiotensin II and sympathetic stimulation (may account for ability of angiotensin II to increase Na reabsorption in hypovolemic states)
69
What is the osmolality of tubular contents in the proximal tubule?
Isotonic
70
Cl-driven Na Reabsorption
As solutes and water are reabsorbed early in proximal tubule, Cl in the latter proximal tubule increases resulting in the development of a favorable concentration gradient for passive reabsorption of Cl through leaky tight junction and is accompanied by Na and water.
Accounts for about 30% of proximal tubular Na and Water reabsorption
71
What portion of the loop of Henle is impermeable to solutes and permeable to water?
Thin Descending Portion
72
What portion of the loop of Henle is permeable to Na and Cl?
Thin Ascending Limb
Na and Cl leave the tubule by passive diffusion down a favorable concentration gradient
73
What portion of the nephron is impermeable to water?
1. Thin Ascending Limb
2. Thick Ascending Limb
3. Distal Tubule
74
What portion is referred to as the diluting segment?
1. Thin Ascending Limb
2. Thick Ascending Limb
3. Distal Tubule
75
Na-K-2Cl Pump
Carrier in the luminal membrane of the thick ascending limb
Stimulated by ADH and Aldosterone to increase medullary interstitial osmolallity facilitating water reabsorption
76
Na-Cl Co-Transporter
* Found in luminal membrane of distal tubule
* Important in control of calcium reabsorption
Blocked by thiazide diuretics
77
The reabsorption of Na and Cl in the connecting segment and cortical collecting tuble is mediated by?
Principal Cells
78
Aldosterone
* Stimulates Na reabsorption in principal cells of collecting tubules/ducts
* Increases NaK-ATPase Activity
* Increases synthesis and insertion of Na channels
* Increases the provision of energy for active transport
* Increases K secretion from principal cells
* Increases H secretion from intercalated
* Only increases Na reabsorption by 3%
* Important in fine control of Na excretion
79
What controls the permeability of the collecting tubules/ducts to water?
ADH
80
What does Na reabsorption decrease in hypervolemic states?
1. Aldosterone decreases
2. ANP stimulates guanylate cyclase in medullary principal cells
1. Cyclic GMP decreases the number of open Na channels in the luminal membrane thereby reducing Na reabsorption
3. Urodilatin blocks Na and water reabsortption in the medullary collecting ducts
81
What controls extracellular fluid volume?
Kidneys
82
The regulation of effective circulating blood volume is dependent on what?
Control of Na reabsorption and secretion
83
Primary Stimuli for Aldosterone Release
1. Angiotensin II
2. Hyperkalemia
3. Hyponatremia
4. ACTH
84
Increase in Na intake will?
* Increase urine Na
* Decrease Plasma Renin
* Decrease Aldosterone
* Increase ECBV
85
ANP and BNP Actions
* Vasodilate afferent arterial which increases GFR and the filtered load of Na leading to increased excretion
* Inhibit renin release from afferent arterioles
* Inhibit Na reabsorption in the collecting tubules causing natriuresis and diuresis
* Inhibit aldosterone secretion
* Inhibit ADH release
86
Urodilatin Actions
Inhibits reabsorption of Na and water reabsorption causing natriuresis and diuresis
Better correlated w/ hypervolemia
87
In hypervolemic states blood flow is shunted to what nephrons?
* Cortical Nephrons
* Have a lower capacity for Na reabsorption than juxtamedullary
88
In hypovolemic states blood flow is shunted toward what nephrons?
* Juxtamedullary Nephrons
* Thought to be associated w/ action of angiotensin II causing greater vasoconstriction in cortical arterioles
89
Angiotensin II Effects
1. Stimulate release of aldosterone to increase Na and Water reabsorption
2. Systemic vasoconstriction to increase blood pressure
3. Stimulates thirst to increase water intake
4. Stimulates ADH release to increase distal nephon water reabsorption in severe cases where ther is \>10% reduction in ECBV
5. Causes greater vasoconstriction of efferent arterioles which
1. Decreases RBF
2. Maintains adequate GFR
3. Increase FF which increases peritubular capillary reabsorption
6. Enhances NE biosynthesis
7. Greater vasoconstriction of outer cortical afferent arterioles
8. Stimulates synthesis of dilatory prostaglandins
9. Stimulates Na reabsorption in proximal tubule via NaK-ATPase
10. Inhibits renin secretion (negative feedback)
90
K Excretion is controlled by adjusting what?
Tubular K Secretion
91
What is the daily filtered load of K, assuming GFR is 180 and plasma K is 4.5
810 mEq
92
what type of cell mediates K reabsorption? How does this work?
intercalated cells, in distal nephron
active process through K-H ATPase and maybe K ATPase
93
What does H ATPase do?
Actively secretes H into the lumen
94
What cells handle K secretion? Where are they located? K secretion is controlled in part by what? What inhibits K secretion?
principal cells; distal nephron; aldosterone; angiotensin II
95
Entry of K into the cell is active and mediated by what?
Na-K ATPase
96
What are factors that influence plasma K concentration?
dietary intake
Na-K ATPase - increases the cewllular load of K and keeps plasma levels low; inhibition of Na-K ATPase can cause rapid and profound hyperK
Insulin - promotes K uptake, rapid rise in insulin s/p meal prevents increases in plasma K
circulating catecholamines - enhance K uptake via beta 2 receptors; beta blockers can result in large increases in plasma K, especially during exercise
Aldosterone - elevated plasma K stimulates aldosterone release, increasing Na reabsorption leading to K secretion; independent of volume change
97
Hyperkalemia stimulates the secretion of what?
Aldosterone which stimulates NaK-ATPase, which increases cellular uptake of K on the basolateral membrane
Also appears to increase the permeability of the luminal membrane to K increasing secretion _secondary to increased Na uptake_
98
What percentage of total plasma Ca is filtered and why?
50% because 50% is bound to plasma albumin and other ions
99
What percantage of the filtered load of Ca is reabsorbed?
99%
100
Active reabsorption of Ca occurs where?
Distal Tubule
101
What percantage of the filtered load of Ca is reabsorbed in the Proximal Tubule? Loop of Henle?
70%
20%
102
Ca reabsorption in the proximal tubule tends to change in parallel with what other ion reabsorption?
Na Reabsorption
103
In the Loop of Henle what helps drive cation reabsorption?
Na-K-2Cl Pump and subsequent K recycling into the lumen creates a Positive Lumen Potential thus driving cation reabsorption
104
What induces the synthesis of calcium binding protein?
Calcitriol
105
What controls Ca reabsorption in the distal tubule?
Parathyroid Hormone
106
Parathyroid Hormone Effects
1. Increases resorption of bone
2. Increases Ca reabsorption in distal tubule
3. Increases phosphate excretion (decrease reabsorption)
107
Phosphate is reabsorbed in the proximal tubule by what?
Secondary Active Na-phosphate cotransporter
108
How is ECF osmolality controlled?
By altering water intake and renal excretion of water
109
Four System Elements that Control Body Fluid Osmolality
1. Loop of Henle (Counter-Current Multiplier) and Vasa Recta (Counter-Current Exchanger) - Creation and Maintenance of Medullary Osmotic Gradient
2. Variable Permeability of Collecting Ducts
3. Osmoreceptors and Thirst Centers
4. ADH
110
Countercurrent Exchange Passive or Active?
Passive
111
Countercurrent Multiplier Passive or Active?
Active
112
What about vasa recta blood flow preserves medullary hypertonicity?
It is sluggish, which prevents washout of the medullary gradient
113
What stimulates hypothalamic osmoreceptors?
Increased ECF Osmolality causing shrinkage of the osmoreceptors and increases ADH release
114
What is ADH more sensitive to, plasma osmolality or plasma volume?
Plasma Osmolality
115
Prerenal Azotemia
116
What is the source of secreted H+?
Hydration of CO2
117
What is the minimal urine pH?
4.5
118
What cells are responsible for bicarbonate secretion?
Type "B" Cells (Subpopulation of Intercalated Cells)
119
Total H+ Secreted Equation
=TA + NH4+ + HCO3-
120
New HCO3- Production
= TA + NH4+
121
Factors that influence H+ secretion
1. Availability of Urinary Bases
2. Increases and Decreases in PaCO2
3. Aldosterone - parallel increase in H and K secretion
1. Excess can cause hypokalemia and met. alkalosis
2. Deficit can cause hyperkalemia and met. acidosis
4. Primary Hyperkalemia
1. Via K-H Exchangers
5. Increase deliver of Na to distal nephron
6. Renal Tubular Acidosis
122
Type 4 RTA
* Inadequate production and excretion of NH4+
* Most often associated w/ aldosterone deficiency or resistance resulting in distal nephron H secretion and hyperkalemia
123
Clearance
Cx = (Vu\*Ux)/Px
124
RPF
=(Vu\*UPAH) / PPAH
125
