Renal IIIa Flashcards
1
Q
Maintenance of body fluid is tied to….
A
regulation of body sodium content
2
Q
What effect does plasma membrane Na-K ATPase pump on Na and K?
A
most body Na is retained within ECF
most body K+ is intracellular
3
Q
Any net increase in total body fluid….
A
is retained in the ECF and body fluid volume increases
4
Q
Any net loss of total body Na results in…
A
decrease in ECF volume
5
Q
___ is critical in the maintenance of body fluid volume
A
Regulation of body Na
6
Q
Increase Na → __ osmolarity → __ H2O
A
Increase Na → increases osmolarity → increases H2O
7
Q
Increase Total - Body Sodium → __ EC Volume (Plasma Volume/Interstitial Volume) → __blood volume → __ venous pressure → __ atrial pressure → __ ventricular pressure → __ stroke volume → __ cardiac output → __ arterial blood pressure → effects __ and directly effects __
A
Increase Total - Body Sodium → ⇡ EC Volume (Plasma Volume/Interstitial Volume) → ⇡ blood volume → ⇡ venous pressure (MV) → ⇡ atrial pressure (MV) → ⇡ ventricular pressure (MV) → ⇡ stroke volume → ⇡ cardiac output → ⇡ arterial blood pressure → effects monitored variables (MV) and directly effects kidneys
8
Q
Sodium Excretion Equation
A
Sodium Excretion = Sodium Filtered - Sodium Reabsorbed
= (GFR X PNa) - Sodium reabsorbed
PNa = plasma concentration of Na
9
Q
It is possible to adjust sodium excretion by…
A
controlling plasma sodium, GFR, and sodium reabsorption
10
Q
What regulates GFR and sodium reabsorption?
A
the kidneys
monitored by alterations in ECF where effectors that regulate ECF simultaneously regulate sodium reabsorption and excretion
11
Q
Changes in Plasma Sodium
A
Plasma sodium changes little except to change transiently after ingestion of sodium rich or sodium-free meal/drink
12
Q
A person is considered in positive Na balance if…
A
excretion is less than Na ingested
retaining water
13
Q
A person is in negative Na balance when…
A
Na excretion is more than Na ingested
net excreting fluid
14
Q
Factors that control GFR and Sodium reabsorption in response to altered bodily sodium balance are initiated by….
A
- Extrarenal baroreceptors
- carotid sinuses, in arteries, cardiac chambers, great veins
- Renal Juxtaglomerular (JG) apparatus
- specifically intrarenal baroreceptors and macula densa which control secretion of renin
15
Q
Extrinsic control of GFR:
A
- Renal sympathetic nerves
- Renin-angiotensin system
16
Q
Extrinsic control of GFR: Renal Sympathetic nerves
A
- increased renal sympathetic nerve activation → increased renal arteriolar constriction → decreased PGC → decreased GFR
- Increases renal sympathetic nerve activation → increased renal arteriolar constriction → decreased renal blood flow → increased average πGC → decreased GFR
17
Q
Extrinsic control of GFR: Renin-Angiotensin System
A
increased renin release → increased plasma Ang II → decreased GFR and RBF
18
Q
Local and Direct regulation of GFR:
A
- Autoregulation
- Prostaglandins
19
Q
Local and Direct regulation of GFR: Autoregulation
A
allows maintenance of a relatively constant GFR over a wide range of perfusion pressures
fine tuning
minute to minute regulation of RBF and GFR in the face of changes in BP
20
Q
Local and Direct regulation of GFR: Prostaglandins
A
PGE2 and PGI2
vasodilators
help make sure too much constriction doesn’t occur
21
Q
Tubular Sodium Reabsorption is mediated by…
A
- aldosterone
- renal sympathetic nerves
- angiotensin II
- pressure natriuresis
- ANP
- ADH (minor effect)
22
Q
Where is aldosterone produced?
A
the adrenal cortex
23
Q
How does aldosterone work?
A
Aldosterone exerts its effect by combining with intracellular receptors and stimulating synthesis of mRNA which mediates translation of specific proteins
The proteins increase the number of luminal-membrane sodium channels and basolateral Na-K-ATPase pumps in the cortical collecting duct (principal cells)
24
Q
3 Major Inputs to the adrenal gland stimulating aldosterone secretion…
A
- Adrenocorticotropic hormone (ACTH)
- Increased plasma potassium
- Angiotensin II
increase any of these → increase aldosterone secretion
25
Anything that increases Ang II, ___ aldosterone
increases
26
Aldosterone acts in the ___ and ___ Na reabsorption
collecting duct; increases
27
Control of aldosterone secretion
Aldosterone attaches to aldosterone receptor → increases number of sodium channels → increases sodium reabsorption
28
Tubular effects of renal sympathetic nerves
* stimulates renin secretion via direction action on β1-receptors of granular cells
* directly stimulates sodium reabsorption in proximal tubule cells
* affect peritubular capillary Starling Forces and FF → constriction of arterioles will decrease RBF more than GFR
* results in decreased peritubular capillary hydrostatic pressure and increased peritubular capillary oncotic pressure → increases sodium reabsorption
* decreased GFR and increased Na reabsorption in proximal tubule → decreases sodium delivery to macula dense which in turn increases renin secretion
29
Increased constriction, ___ Filtration Fraction (FF)
increases
FF increases with sympathetic nervous activity that increases capillary oncotic pressure (driving force of Na reabsorption)
30
Tubular effects of Ang II: Direct effects
Angiotensin II acts directly on proximal tubule cells to stimulate sodium reabsorption → this is done by stimulating the Na-H+ exchanger in the proximal tubule
31
Tubular effects of Ang II: Effects on FF and Peritubular Capillary Starling Forces
Increases FF and thus increases Na and water reabsorption in proximal tubule
32
Tubular effects of Ang II: Aldosterone
increase aldosterone secretion
33
Tubular effects of Ang II: Ang II
Ang II has a profound effect on Na reabsorption by itself
34
What secretes Atrial Natriuretic Peptide (ANP)?
Cardiac Atrial Cells
35
How is ANP released?
Distention of the atria occurs during plasma volume expansion and ANP is released which acts directly on the inner medullary collecting ducts to inhibit sodium reabsorption
36
Atrial Natriuretic Peptide (ANP)
inhibits sodium reabsorption
increases Na excretion
37
ADH (vasopressin)
Increases reabsorption of Na from the thick ascending limb, distal tubule and collecting duct
38
Water Excretion
Water excretion = volume filtered (GFR) - volume reabsorbed
39
What is the main determinant of water excretion?
the rate of water reabsorption → this is mainly determined by ADH levels
40
Control of ADH secretion
baroreceptors and/or osmoreceptors
41
What is the major function of ADH?
major function of ADH is to increase the permeability of the cortical and medullary collecting ducts to water, thereby decreasing excretion of water
increases Na reabsorption by the cortical collecting duct → effect on total sodium reabsorption is very small
42
Baroreceptor Control of ADH Secretion
⇣ plasma volume → ⇣ venous, atrial, and arterial pressures → ⇡ activation of reflexes mediated by cardiovascular baroreceptors → ⇡ ADH secretion → ⇡ Plasma ADH → ⇡ collecting duct permeability to H2O → ⇡ H2O reabsorption → ⇣ H2O excretion
43
Osmoreceptor Control of ADH Secretion
Excess H2O ingested → ⇣ extracellular-fluid osmolarity (⇡ H2O concentration) → reflex mediated by osmoreceptors → **⇣ ADH secretion** → ⇣ Plasma ADH → ⇣ collecting duct permeability to H2O → ⇣ H2O reabsorbed → ⇡ H2O excreted
44
⇡ Osmolarity (lose water) → __ ADH secretion → __ water reabsorption
⇡ Osmolarity (lose water) → ⇡ ADH secretion → **⇡** water reabsorption
45
Thirst response
centers that mediate thirst are located in the hypothalamus
thirst is stimulated by reduced plasma volume and increased body-fluid osmolarity
46
⇣ plasma volume → ___ Ang II → stimulates ____ in the kidneys
⇣ plasma volume → ⇡ Ang II → stimulates **Na reabsorption** in the kidneys
47
Effect of Ang II on thirst
Ang II stimulates thirst by a direct effect on the brain
Ang II stimulates ADH release from the posterior pituitary which increases water reabsorption
48
Define: Euvolemia
normal ECF volume
49
Control of Renal NaCl excretion during Euvolemia
* Na reabsorption by proximal tubule and Loop of Henle is regulated so that a relatively constant portion of filtered Na is delivered to distal tubule.
* These two segments reabsorb approximately 90% of sodium and ensure that approximately 10% gets delivered to distal tubule
* Reabsorption of remaining filtered sodium by distal tubule and collecting duct is regulated so that amount of Na in the urine closely matches the amount ingested in diet at steady state
50
Mechanisms for maintaining constant Na+ delivery to the distal tubule (during euvolemia)
* Autoregulation
* Glomerular tubular balance
* Sympathetic activity to maintain GFR and increase Na+ reabsorption in proximal tubule
* Ang II to maintain GFR and increase Na+ reabsorption in proximal tubule
* Local metabolites (prostaglandins, NO, dopamine) which try to maintain GFR
51
Glomerular Tubular Balance
mechanism tries to maintain % of Na and water reabsorbed, particularly in the proximal tubule constant
no nerves or hormones involved
⇡ filtered load, ⇡ reabsorption to 60-65%
52
Mechanisms for regulating Na+ reabsorption in the distal tubule and collecting duct
Aldosterone
ANP
ADH (minor function)
53
ECF volume contraction → renal perfusion pressure is ___ → renal plasma flow is ___ → PGC is ___ → ___ in πGC → GFR is ___ → ____ salt and water excretion
ECF volume contraction → renal perfusion pressure is **decreased** → renal plasma flow is **decreased** → PGC is **decreased** → **increase** in πGC → GFR is **decreased** → **decreased** salt and water excretion
54
ECF volume contraction → ___ renal sympathetic nerve activation → ___ constriction of renal arterioles → ___ GFR → __ salt and water excretion
ECF volume contraction → **increased** renal sympathetic nerve activation → **increased** constriction of renal arterioles → **decreased** GFR → **decreased** salt and water excretion
55
ECF volume contraction → plasma oncotic pressure is ___ → directly ___ GFR→ __ salt and water excretion
ECF volume contraction → plasma oncotic pressure is **increased** → directly **decreases** GFR→ **reduces** salt and water excretion
56
ECF volume contraction → ___ renal sympathetic nerve activation → ___ constriction of renal arterioles → ___ RBF more than GFR → Filtration Fraction ___ → __ reabsorption of NaCl in proximal tubule
ECF volume contraction → **increased** renal sympathetic nerve activation → **increased** constriction of renal arterioles → **decreased** RBF more than GFR → Filtration Fraction **increased** → **increased** reabsorption of NaCl in proximal tubule
57
ECF volume contraction → ___ renal sympathetic nerve activation → __ NaCl reabsorption in proximal tubule
ECF volume contraction → **increased** renal sympathetic nerve activation → **increased** NaCl reabsorption in proximal tubule
58
ECF volume contraction → ___ renin secretion (through various mechanisms) → ___ plasma Ang II → ___ GFR → __ salt and water excretion
ECF volume contraction → **increased** renin secretion (through various mechanisms) → **increased** plasma Ang II → **decreased** GFR → **decreased** salt and water excretion
59
ECF volume contraction → ___ renin secretion (through various mechanisms) → ___ plasma Ang II → ___ RBF more than GFR → Filtration Fraction ___ → __ salt and water reabsorption in proximal tubule
ECF volume contraction → **increased** renin secretion (through various mechanisms) → **increased** plasma Ang II → **decreased** RBF more than GFR → Filtration Fraction **increases** → **increased** salt and water reabsorption in proximal tubule
60
ECF volume contraction → ___ renin secretion (through various mechanisms) → ___ plasma Ang II → ___ Na reabsorption through Na/H+ antiporter in proximal tubule
ECF volume contraction → **increased** renin secretion (through various mechanisms) → **increased** plasma Ang II → **increased** Na reabsorption through Na/H+ antiporter in proximal tubule
61
ECF volume contraction → ___ renin secretion (through various mechanisms) → ___ plasma Ang II → ___ aldosterone secretion → ___ Na reabsorption in late distal and collecting ducts
ECF volume contraction → **increased** renin secretion (through various mechanisms) → **increased** plasma Ang II → **increased** aldosterone secretion → **increased** Na reabsorption in late distal and collecting ducts
62
ECF volume contraction → ___ ADH plasma levels → ___ water reabsorption in collecting tubule
ECF volume contraction → **increased** ADH plasma levels → **increased** water reabsorption in collecting tubule
63
ECF volume contraction → ___ stretch of atria walls → ___ ANP secretion → ___ ANP mediated natriuresis
ECF volume contraction → **decreased** stretch of atria walls → **decreased** ANP secretion → **decreased** ANP mediated natriuresis
64
What happens to volume contraction or expansion during pathological conditions?
local and autoregulatory mechanisms are “overridden” by the neurohumoral compensatory mechanisms which are activated
65
Congestive Heart Failure
Patient with failing heart → kidneys try to compensate for heart failure → increases heart failure
Patient with failing heart → decreased CO → decreased renal perfusion pressures → decreased GFR → increased activity of renin-angiotensin-aldosterone system and renal sympathetic nerves → increased sodium retention even when patient is in positive sodium balance → causes edema
66
Neurohumoral compensatory pathways
* sympathetic nervous stimulation
* activation of renin-angiotensin system
* increase ADH release
* increase aldosterone
pathways lead to greater salt and water retention which exacerbates edema
67
Hyponatremia
plasma Na+ concentration of less than 135 mEq/L w/ osmolarity to \< 275 mOsm/L
too much water
⇡ ADH release → ⇡ H2O reabsorption → causes hyponatremia
usually occurs in heart failure b/c you're absorbing more water than Na
68
Most common cause of hyponatremia is…
dysregulation of ADH secretion → “syndrome of inappropriate ADH secretion (SIADH)”
increased ADH release from posterior pituitary → results in high levels of water reabsorption from the collecting duct and hyponatremia (too much water)
69
Hypernatremia
plasma Na+ concentration \> 145 mEq/L w/ osmolarity to \> 295 mOsm/L
ADH dysregulation
70
Causes of hypernatremia
* decreased ADH release from posterior pituitary → causes massive output of hypoosmotic urine and hypernatremia
* Plasma ADH is relatively normal → tubule response to circulating hormone is severely depressed → increased hypoosmotic urinary output → hypernatremia
71
ECF volume expansion → renal perfusion pressure is ___ → renal plasma flow is ___ → PGC is ___ → ___ in πGC → GFR is ___ → ____ salt and water excretion
ECF volume expansion → renal perfusion pressure is **increased** → renal plasma flow is **increased** → PGC is **increased** → **decrease** in πGC → GFR is **increased** → **increased** salt and water excretion
72
ECF volume expansion → ___ renal sympathetic nerve activation → ___ constriction of renal arterioles → ___ GFR → __ salt and water excretion
ECF volume expansion → **decreased** renal sympathetic nerve activation → **decreased** constriction of renal arterioles → **increased** GFR → **increased** salt and water excretion
73
ECF volume expansion → plasma oncotic pressure is ___ → directly ___ GFR→ __ salt and water excretion
ECF volume contraction → plasma oncotic pressure is **decreased** → directly **increases** GFR→ **increase** in salt and water excretion
74
ECF volume expansion → ___ renal sympathetic nerve activation → ___ constriction of renal arterioles → ___ RBF more than GFR → Filtration Fraction ___ → __ reabsorption of NaCl in proximal tubule
ECF volume expansion → **decreased** renal sympathetic nerve activation → **decreased** constriction of renal arterioles → **increased** RBF more than GFR → Filtration Fraction **decreases** → **decreased** reabsorption of NaCl in proximal tubule
75
ECF volume expansion → ___ renal sympathetic nerve activation → __ NaCl reabsorption in proximal tubule
ECF volume expansion → **decreased** renal sympathetic nerve activation → **decreased** NaCl reabsorption in proximal tubule
76
ECF volume expansion → ___ renin secretion (through various mechanisms) → ___ plasma Ang II → ___ GFR → __ salt and water excretion
ECF volume expansion → **decreased** renin secretion (through various mechanisms) → **decreased** plasma Ang II → **increased** GFR → **decreased** salt and water excretion
77
ECF volume expansion → ___ renin secretion (through various mechanisms) → ___ plasma Ang II → ___ RBF more than GFR → Filtration Fraction ___ → __ salt and water reabsorption in proximal tubule
ECF volume expansion → **decreased** renin secretion (through various mechanisms) → **decreased** plasma Ang II → **increased** RBF more than GFR → Filtration Fraction **decreases** → **decreased** salt and water reabsorption in proximal tubule
78
ECF volume expansion → ___ renin secretion (through various mechanisms) → ___ plasma Ang II → ___ Na reabsorption through Na/H+ antiporter in proximal tubule
ECF volume expansion → **decreased** renin secretion (through various mechanisms) → **decreased** plasma Ang II → **decreased** Na reabsorption through Na/H+ antiporter in proximal tubule
79
ECF volume expansion → ___ renin secretion (through various mechanisms) → ___ plasma Ang II → ___ aldosterone secretion → ___ Na reabsorption in late distal and collecting ducts
ECF volume expansion → **decreased** renin secretion (through various mechanisms) → **decreased** plasma Ang II → **decreased** aldosterone secretion → **decreased** Na reabsorption in late distal and collecting ducts
80
ECF volume expansion → ___ ADH plasma levels → ___ water reabsorption in collecting tubule → __ water excretion
ECF volume expansion → **decreased** ADH plasma levels → **decreased** water reabsorption in collecting tubule → **increased** water excretion
81
ECF volume expansion → ___ stretch of atria walls → ___ ANP secretion → ___ ANP mediated natriuresis
ECF volume expansion → **increased** stretch of atria walls → **increased** ANP secretion → **increased** ANP mediated natriuresis
82
Congestive Heart Failure Map
