Lecture 17 Flashcards
total body water___% of body weight and ____ L
60% 42 L
intracellular fluid accounts for ___ L and extracellular accounts for ____
28 L
12 L
intracellular fluid contains _____ and _______ which involve _______
cations
- K+
- Mg-
anions
- PO4
- proteins
extracellular fluid includes ___ L from _____ and ___ L from ______.
also has cations _____ and anions _____
3 L from plasma
11 L from interstitium
Na+
Cl and bicarb
can get up to ___ L per day in sweat output
5
common trigger in blood loss requiring the conservation of salt and water
sympathetic stimulation
sympathetic stimulation also triggers kidneys to reduce __________, stimulate __________, and promote ______
GFR and renal blood flow
Na+ reabsorption
renin release
Major route of Na+ loss excreting ___% of ingested Na+ if needed
Ability to adjust this amount depending on the clinical demand “Effector”
- Increase in _________ causes kidneys to lose Na+
95%
ECF volume
abnormal Na+ retention occurs in _____, _____, and _____
intravascular plasma
within the vascular system
transcellular fluid as part of ECF compartment
when there is abnormal sodium retention, fluid shift from the _____ to the ______. the fluid shift is caused by _______
intravascular
interstitial space
increase in capillary pressures pushing fluid out of the blood vessels
example of expansive of the interstitial space ?
congestive heart failure
expansion of interstitial space includes…
- Peripheral ______
- Elevated venous pressure resulting in elevated hydrostatic pressure causing the “________”
- Inadequate ____ function results in perceived reduction in blood volume
edema
capillary leak
pump
inadequate pump function results in …
Reduced GFR
Increase renin-angiotensin-aldosterone activity
Increased sympathetic activity leading to renal salt and water retention
defined as the rate at which plasma is filtered by the kidney glomeruli
Glomerular filtration rate (GFR)
- important measure of kidney function
Determining Kidney Function Using Glomerular Filtration Rate (GFR)
- Ideally, a substance that is cleared from the plasma solely by glomerular filtration, would be an excellent measure of GFR.
- This substance was found in the ______ polymer _____
fructose
inulin
Why is inulin a good measurement for GFR?
It’s _____ (it’s a plant polysaccharide, a form of soluble fiber)
Freely filterable by the glomeruli
Not__________ by the kidney tubules
Not _________________ in the kidneys
Its concentration in plasma and urine can be simply analyzed
nontoxic
reabsorbed or secreted
synthesized, destroyed, or stored
The filtered load of inulin is equal to the rate of inulin excretion.
PIN X GFR = UIN x V
Because of this, we can rearrange the equation as:
GFR= (UIN x V)/PIN = CIN
This makes ______________.
inulin clearance a direct measure of GFR
Is Inulin the Easiest Clinical Measure of GFR?
Not commonly used clinically due to need for intravenous administration and catheterization, making this complicated and inconvienient
simpler to use a substance that is endogenous to the human body
Do we have an endogenous substance that is only filtered, excreted in the urine, and maintained at stable plasma levels…..?
no but we have one that comes close (creatine)
Creatinine as a candidate:
- End product of _________ and a derivative of ________
- Produced continuously
- Excreted in the urine
- Can be collected over long urine collection periods (hours to 24 hours)
- Levels are normally stable in the plasma
- Does not have to be infused
muscle metabolism
muscle creatine phosphate
Creatinine Clearance as a Measure of GFR calculation
Creatine = (Ucreatine)(x)(V)
___________________
Pcreatine
x is the substance (creatinine here)
Cx is the clearance of substance x
Ux is the urine concentration of substance x
Px is the plasma concentration of substance x
V is the urine flow rate.
Clinical estimation of creatinine clearance
Cockroft-gault Equation
male vs female Cockroft-gault Equation
Males:
GFR (ml/min) = ((140- age in years) x bodyweight in kg)/(72 x serum creatinine in mg/dl)
Females:
GFR (ml/min) = 0.85 x ((140- age in years) x bodyweight in kg)/(72 x serum creatinine in mg/dl)
The driving force for glomerular filtration is the __________ across the glomerular _______
net ultrafiltration pressure
capillaries
a product of the intrinsic permeability of the glomerular capillary and the glomerular surface area available for filtration
Equation ?
The glomerular capillary filtration coefficient (Kf)
Kf = GFR/ Net filtration pressure
Filtration is always favored: The rate of filtration in the glomerulus is much _____ than in systemic capillaries. Mainly because Kf is approx. _________ in glomerular capillaries
greater
100x greater
Glomerular capillary hydrostatic pressure is about _______ as the hydrostatic pressure in other systemic capillaries.
Thus GFR can be altered by changes in ___, and/or the starling forces.
twice as great
Kf
What is the net ultrafiltration pressure?
Represents the sum of the hydrostatic and colloid osmotic forces that either favor or oppose filtration across the glomerular capillaries
GFR= Kf[(PGC-PBS) – (πGC – πBS)]
Glomerular capillary hydrostatic pressure
(PGC: promotes filtration)
increased by dilation of the afferent arteriole or constriction of the efferent arteriole
The hydrostatic pressure in Bowman’s capsule
(PBS: opposes filtration)
increases by constriction of the ureters
increases in PBS cause decreases in net ultrafiltration pressure and GFR.
The glomerular capillary oncotic pressure or blood colloid osmotic pressure
(πGC : opposes filtration)
increases along with protein concentration
normally decreases net ultrafiltration pressure and GFR
Bowman’s space oncotic pressure
(πBS: promotes filtration)
under normal conditions the protein in the glomerular filtrate is so low that the πBS is considered to be zero
At the glomerular capillary:
PGC= 45 mm Hg,
PBS = 10 mm Hg
πGC= 27 mm Hg
calculate net pressure
Net pressure = (PGC – PBS)- πGC
Net pressure = (45 mm Hg – 10 mm Hg) –27 mm Hg
= 8 mm Hg (favoring filtration)
What are these variables influenced by?
- Sympathetic nervous system output
- Hormones and vasoactive substances that are released in the kidney and act locally
- Other feedback controls that are intrinsic to the kidney
- efferent arteriole
- smooth muscle fiber
- distal tubule
- macula densa
- basement membrane
- internal elastic lamina
- afferent arteriole
- juxtaglomerular cells
- glomerular epithelium
urine output when arterial pressure increases curve is ____________.
renal urinary output curveor arenal function curve
At an arterial pressure of ____ mm Hg, the urine output is approximately zero.
At around ____ mmHg it is normal, and at
_____ mm Hg it is about six to eight times normal
50
90
200
Increased urinary output in this curve is partially due to __________-. (Sodium output increases as well- pressure natriuresis)
pressure diuresis
Renal output and Salt and water intake determine _______because of volume changes in the blood
At the Equilibrium point, normal intake of water and salt gives us a normal Mean Average Pressure (_________).
Arterial pressure
100mmHg +/-
Areas of fluid adjustment in the kidney include….
- Formation of an _________ across the glomerulus
- Fluid passes through the tubules - modified:
_______ -removal of a substance from the filtrate
_______ -addition of a substance to the filtrate - Different tubular segments contribute to this process
ultrafiltrate of plasma
Reabsorption
Secretion
osmoreceptors are located in the ______ which sense ___ concentration.
this concentration is also the primary osmotic determinant of anti-diuretic hormone release (ADH)
hypothalamus
Na+
Osmotic threshold for ADH release is about _______ mosmol/kg
280 to 290
antidiuretic causes _____ fluid to be held in the bloodstream and ______ solutes.
more
dilutes
Renal
- Antidiuretic hormone acts on the ________ making them _____ permeable to water, and water gets reabsorbed instead of lost to urine
- Driven by the amount of solute (“________”) of the filtrate
distal tubules
more
hypertonicity
osmoregulation impacts _____ levels
volume regulation impacts _____ levels
water
solute
Regulation of fluid volume and concentration occurs through the interaction of 2 hormones:
ADH: retention of water
Aldosterone: retention of sodium
Regulation of Fluid Balance
- Arginine vasopressin (ADH)
- Renin-Angiotensin –aldosterone System
- Hydrostatic Pressure
- Natriuretic Hormones
- Miscellaneous
- Regulator of water reabsorption
- Sodium balance
- K+ secretion by the renal tubules - Atrial Natriuretic peptide
- Minor role in inhibiting both electrolyte and water reabsorption - hormones, sympathetic stimulation, diuretics
Role of ADH
__________ synthesized in the Hypothalamus and transported via the axons of the hypothalamohypophyseal tract to the posterior _______
Major stimuli hyperosmolality and volume _____
arginine vasopressin
hypothalamohypophyseal
pituitary lobe
depletion
ADH regulates water reabsorption by increasing water permeability of the ________ in the __________
These cells house tiny vesicles containing copies of a water channel protein called __________
ADH stimulates insertion of the channels into the apical membranes
principal cells
DCT and collecting ducts
aquaporin-2
insertion of the aquaporin-2 channels into the membrane results in an increase of water permeability of the apical membrane allowing water molecules to move more rapidly through the tubular fluid into the cells
_____________ is then produced
Concentrated urine (more yellow)
In the absence of ADH, principal cell membranes have a very low permeability to water resulting in a _______
dilute urine
ADH receptors use _____ to activate ____________, causing cytoplasmic vesicles containing Aquaporin -2 ADH sensitive water channels fuse to luminal membrane allowing rapid water reabsorbtion to the systemic circulation
ADH effect wears off, the water channels aggregate, are then removed by __________ and returned to the cytoplasm
cAMP
protein kinase A
endocytosis
ADH mechanism maintains precise control of _______ fluid osmolarity and ______ concentration
Thirst center poorly localized area of the hypothalamus
- Osmoreceptors in the hypothalamus respond to dehydration
- increased ________ in the circulating blood by increasing the production and release of ADH
- triggers include ________ and ________
extracellular
Na+
osmolality
increased osmolality/ NaCl
hypovolemia
There are 2 ways in which fluid volume can increase Arterial Pressure
1: Increased Cardiac Output (and increased venous return of that fluid volume)
2: Increased total peripheral resistance, which, through autoregulation, causes constriction of blood vessels to maintain normal levels of blood flow through the capillary beds of the body.
*Arterial Pressure = Cardiac Output x total peripheral resistance
increased salt intake results in
increased ______ volume and
increased ____ pressure,
decreased ____ and _____,
________ renal retention of salt and water
return of _____ volume to almost normal
return of _____ pressure to almost normal
extracellular
arterial
renin and angiotensin
decreased
extracellular
arterial
Angiotensin I
____ is released by the____________ of the kidney in response to low pressures.
The cells are ________ cells in the walls of the ______ arterioles
lasts _________ in the circulation, where it induces a substance called Angiotensin I.
Angiotensin I is a mild ______________.
Renin
Juxtaglomelular cells (JG cells)
smooth muscle
afferent and efferent
30 minutes to an hour
vasoconstrictor
Conversion of Angiotensin I to Angiotensin II within ____________ within the ________ of the _____. Renin remains in circulation and continuously pushes this reaction.
seconds to minutes
small vessels
lungs
AT I to AT II is catalyzed by ____________, which is found in the small vessels of the _______, and in small amounts in the _____ and small vessels peripherally.
Angiotensin Converting Enzyme (ACE!)
lungs
kidney
AT II lasts a ______ period of time, but is ______.
It _______ arterioles peripherally, and also acts to _______ excretion in the kidneys of salt and water.
This______ the extracellular fluid volume, and pressure ______ for hours to days.
short
very powerful
vasoconstricts
decrease
raises
increases
AT II mechanism of salt and water retention
- Acts directly on the kidneys to cause salt and water ______ during low systemic pressure or volume situations.
- Angiotensin II causes the adrenal glands to secrete _______, which in turn ______ salt and water reabsorption by the kidney tubules
which one is more powerful
retention
aldosterone
increases
1 is more powerful by 3-4 times
How does ATII act directly on the kidneys to cause salt and water retention during low systemic pressure or volume situations?
By constricting the arterioles at the Glomerulus.
EFFERENT>afferent, causing flow to remain normal despite low pressures of volume depletion (low salt diet, or dehydration).
Afferent still allows some flow to come in, efferent limits relative outflow.
This way flow is maintained, and kidney pressures stay in the 80-170 mmHg pressure range that it prefers.
_____ is the most powerful stimulator of Aldosterone release (by the ______ glands).
When the Renin-Angiotensin system is activated, aldosterone is typically ______.
Aldosterone causes sodium reabsorption. Then…
FLUID FOLLOWS SOLUTE!
Water retention _______ volume, and causes further pressure _____.
AT II
adrenal
increased
increases
increases
The majority of patients with hypertension are overweight.
Obesity accounts for_____% of the risk factors for essential hypertension.
65-75%
Four reasons obesity causes hypertension?
Cardiac Output increased to supply extra tissue and extra tissue increases resistance.
Increased Sympathetic Nervous system activity is thought to result from hormone release from fat cells which directly stimulate the hypothalamus, resulting in vasomotor constriction peripherally.
Angiotensin II and aldosterone increases 2x-3x in obese individuals as a result of Sympathetic nerve activity
Increased Sympathetic nerve activity increases renal tubular reabsorption of salt and water which raises pressures
