Renal Flashcards
What is homeostasis?
tendency of the body to seek and maintain a condition of balance or equilibrium within its internal environment, even when faced with external changes
The total body water (TBW) makes up how much of the body weight?
60%
ICF
Intracellular Fluid
ECF
Extracellular Fluid
How much of the body fluid is ICF?
2/3 of body fluid
How much of the body weight is ICF?
40% of body weight
How much of the body fluid is ECF?
1/3 of body fluid
How much of the body weight is ECF?
20% of body weight
What 3 things make up the ECF?
- Interstitial fluid (ISF)
- Intravascular fluid (IVF)
- Transcellular fluid (TCF)
What percentage of body weight is ISF?
15% of body weight
What percentage of body weight is IVF?
5% of body weight
What is one of the most important functions of the kidney?
maintain composition and vol. of the ECF
Na+ in plasma?
142 mEq/L
Na+ in ISF?
145 mEq/L
Na+ in ICF?
12 mEq/L
K+ in plasma?
4.3 mEq/L
K+ in ISF?
4.4 mEq/L
K+ in ICF?
150 mEq/L
Ca2+ in plasma?
5 mEq/L
Ca2+ in ISF?
2.4 mEq/L
Ca2+ in ICF?
4 mEq/L
Mg2+ in plasma?
3 mEq/L
Mg2+ in ISF?
1.5 mEq/L
Mg2+ in ICF?
34 mEq/L
Cl- in plasma?
104 mEq/L
Cl- in ISF?
117 mEq/L
Cl- in ICF?
4 mEq/L
HCO3- in plasma?
24 mEq/L
HCO3- in ISF?
27 mEq/L
HCO3- in ICF?
12 mEq/L
Phosphates in plasma?
2 mEq/L
Phosphates in ISF?
2 mEq/L
Phosphates in ICF?
40 mEq/L
Proteins in plasma?
14 mEq/L
Proteins in ISF?
0 mEq/L
Proteins in ICF?
54 mEq/L
What is osmotic pressure?
the force that a dissolved substance exerts on a semipermeable membrane, through which it cannot penetrate, when separated by it from pure solvent
With osmotic pressure, the vol of a given compartment depends on what?
number of solute particles in that compartment
With osmotic pressure, the vol of a given compartment does NOT depend on what?
any specific property of the solute, such as charge, size, or shape
2 ways water crosses cell membranes
- between lipids of bilayer
- through specialized channels called aquaporins
Is it fast or slow for water to cross between lipids of the bilayer?
slow
Is it fast or slow for water to cross through aquaporins?
fast
T/F: An osmotic gradient is required to govern water movement across a membrane.
True
What is oncotic pressure?
osmotic pressure that is exerted by large molecules in a solution
AKA “colloid osmotic pressure’
How does the body govern how much fluid is in a particular compartment? (3 things)
- osmotic pressure
- hydrostatic pressure
- oncotic pressure
What is the impact of oncotic pressure for trans-membrane water flux?
negligible
What is the impact of oncotic pressure for trans-capillary fluxes?
significant
How is homeostasis maintained when conditions change/
Concept of “Set Point”
- system requires sensors/ detectors
- coordination of sensed signals
- feedback and adjustment mechanisms: effectors
Functions of the Kidney (7 things)
- regulation of water and electrolyte balance
- excretion of metabolic waste
- excretion of drugs and hormones
- regulation of arterial blood pressure
- production of erythropoietin
- conversion of vit. D to active form
- gluconeogenesis
What is the basic functional unit of the kidney?
nephron
3 Generally Categories of Kidney Functions
- Filtration
- Absorption/Reabsorption
- Secretion
T/F: Secretion is not the same thing as excretion
True
What causes the production of erythropoietin?
decrease in oxygen tension
In the renal corpuscle,what things are used for solute discrimination?
- size
- shape
- charge
Where are the bulk of filtered solutes reabsorbed?
proximal tubule
What are the juxtamedullary nephrons important for?
concentrating mechanisms
Thick ascending limb (Loop of Henle)
- high ACTIVE transport of NaCl - REQUIRES ATP
- No H2O permeability
Thin descending limb (Loop of Henle)
- High H2O permeability
- No NaCl permeability
Thin ascending limb (Loop of Henle)
- High NaCl permeability
- No H2O permeability
How is the medullary hypertonicity established and maintained?
By the selective permeabilities of loop of Henle segments
What is the medullary hypertonicity necessary for?
concentrating mechanism
Tubular fluid in the distal tubule is ____________.
hypotonic
Role of macula densa cells?
-sense salt load = very sensitive to NaCl concentrations
Tubuloglomerular feedback?
mechanism by which both renal blood flow and glomerular filtration rate are controlled
What cells make up the juxtaglomerular apparatus?
- mesangial cells
- granular cells of the afferent arteriole
Absorption of what happens in the distal convoluted tubule?
- Na+
- Ca2+
- Cl-
What are the cells of the connecting tubule like?
mix of DCT- and CD-like cells
How much of the cardiac output do the kidneys receive?
1/5
What is the percentage of plasma in the blood received by the kidneys?
50-55%
How much of the plasma delivered to the kidneys crosses into Bowman’s capsule?
20-35%
How much of the filtered plasma is excreted?
less than 1%
Where does filtration occur?
interface between vascular and epithelial structures
What determines the permeability across the glomerular filtration barrier?
- size
- charge
- shape
In health, the oncotic pressure in the lumen of Bowman’s capsule should equal?
0 mmHg
How can the glomerular filtration be regulated?
- hormonal
- autoregulation
- tubuloglomerular feedback
What is the stimulus for the renin-angiotensin-aldosterone system?
drop in blood pressure
What is the response for the renin-angiotensin-aldosterone system?
adjust vascular resistance and circulating blood vol.
Where is renin made?
granular cells of afferent arterioles
What is angiotensin?
- peptide
- circulates
- made by liver
Where is ACE made?
endothelial cells of lungs and kidneys
What is aldosterone?
- steroid
- made in adrenal cortex
What does excessively high GFR result in?
elevated tubular flow rates and inefficient removal of NaCl by TALH
What cells sense the high tubular NaCl?
macula densa cells
After sensing high tubular NaCl, the macula densa cells release ATP and adenosine. What does that do?
- INCREASES glomerular mesangial cell constriction
- DECREASES available glomerular capillary filtration area, and hence, Kf
What is clearance?
the volume of plasma from which a substance is completely removed by the kidney in a given amount of time (usually a minute)
How can clearance be a measure of GFR?
clearance of a special substance can be used to measure GFR
Why is inulin ideal for measuring GFR?
- freely filtered
- non-toxic
- not secreted
- not absorbed
- not metabolized
- Cin = GFR
T/F: GFR and inulin clearance do NOT depend on [Pin}
True
As inulin needs to be infused constantly to measure GFR, what is another substance that can be used?
creatinine
Characteristics of creatinine
- normal product of protein metabolism
- production does not vary sig. w/ time
Pro of using inulin?
Cin = GFR
Cons of using inulin?
- requires IV and constant infusion
- requires complete bladder emptying before and after the test
- urine flow must be high to obtain enough urine sample
Pros of using creatinine?
- Ccr ~ GFR
- endogenous; no need for IV or infusion
- can collect urine sample over longer period of time
Con to using creatinine?
secretion can produce an overestimate of GFR
- gen. doesn’t d/t limitations of test
Transcellular transport
through the cell
Paracellular transport
between cells
Absorption
- endocytosis
- transcytosis
Secretion
exocytosis of stored or newly synthesized proteins
Types of transport proteins
- pumps
- carriers
- channels
Types of carriers
- symporters = cotransporters
- antiporters = exchangers = countertransporters
- uniporters
Transport processes
- active
- secondary active (coupled carriers)
- passive (channels, some carriers)
How many sodium does the Na+/K+ pump move out of the cell?
3
How many potassium does the Na+/K+ pump move into the cell?
2
In a healthy individual, how much of the filtered glucose is reclaimed in the PT?
virtually ALL of it!
Why is glucosuria seen in diabetes mellitus?
The PT glucose transport rate is exceeded
Diabetes Mellitus Type I
insulin deficient = inability of pancreas to secrete insulin
Diabetes Mellitus Type II
insulin resistant = target tissues do not respond to insulin
may also be insulin-insufficient
What mediates the proximal tubular reabsorption of HCO3-?
sodium gradient
T/F: HCO3- reabsorption does not rely on the gradient maintained by the Na+/K+ ATPase
False.
It does rely on the gradient.
What does the PT efficiently recover? (3)
- filtered amino acids
- oligopeptides
- low molecular weight proteins (LMPs)
How does Cl- mediated Na+ transport work? (3)
- early PT, lumen (-) potential difference; late PT, luminal [Cl-] increased
- “leaky” tight junctions
- sodium follows chloride
Percentage of filtered Na+ (re)absorbed in the PT?
~65%
Recovery of filtered LMPS via transcytosis in the proximal tubule (4 steps)
- endocytosis of LMPs
- fusion w/ lysosome
- lysosomal degradation and fusion w/ multivesicular body
- transport of amino acids to interstitial space
Transport by the thin segments of the Loop of Henle are ______________.
passive
NaCl transport by TAL is _______.
active
The active transport of NaCl by the TAL reclaims how much more of the filtered NaCl load?
25%
K+ and Cl- move __ their concentration gradients in TAL.
UP
As the TAL is not permeable to water, what happens to the luminal fluid?
It is diluted
What do loop diuretics affect? Examples?
Affect TAL
Examples
- bumetanide (bumex)
- furosemide (lasix)
What is Bartter syndrome?
human dz d/t loss of function mutation
Symptoms of Bartter syndrome? (5)
- present w/ hypotension and salt wasting
- NaCl absorption is impaired
- insufficient dilution of luminal fluid results
- high medullary interstitial tonicity cannot be achieved
- overall renal concentration mechanism is compromised!
T/F: Na+ gradient also drives NaCl uptake by the distal tubule (DT)
True
T/F: the apical transporter in the DT depends on the presence of K+
FALSE
Apical transporter in the DT does NOT depend on the presence of K+
What do thiazide diuretics affect? Example?
Affect DT
Example
-chlorothiazide (diuril)
What is DT Ca2+ absorption regulated by?
parathyroid hormone (PTH)
Cells of the Collecting Duct System (2 categories)
- Intercalated
- Principle
Types of intercalated cells
- alpha
- beta
What do alpha intercalated cells secrete?
acid
What do beta intercalated cells secrete?
base
What intercalated cells are found more in carnivores?
alpha
what intercalated cells are found more in herbivores?
beta
What type of cells predominate throughout all segments of the CD?
priniciple cells
What is the function of epithelial Na+ channels (ENaC)?
permits downhill movement of Na+ from tubular lumen and into cell
ENaC abundance and activity is regulated by?
aldosterone
How is the ENaC put together?
assembly of 3 subunits encoded by 3 genes belonging to a large cation channel gene family
what is something that inhibits ENaC, therefore blocking Na+ absorption?
amiloride
PHA Type I (humans)
- loss of function mutations in ENaC (alpha, beta, and gamma)
- leads to renal salt wasting
Liddle Syndrome (humans)
- gain of function mutations in ENaC (beta and gamma)
- increased renal Na+ uptake
- hypertension
The water permeability of the collecting duct principle cells is modulated by?
ADH (anti-diuretic hormone)
How does ADH affect water permeability of CD principle cells?
- binding of circulating ADH to its basolaterally-localized receptor increases intracellular cAMP
- this then stimulates the fusion of vesicles to the apical membrane
- water exits via aquaporins 3 and 4
Aquaporin 2 contains __________ and is regulated by __________.
pre-synthesized water channels; ADH
As aquaporins 3 and 4 are always around, do they need ADH stimulation?
no
AQP2 and CD ADH-regulated water permeability
Loss of Function Mutation
- NEPHROGENIC diabetes insipidus (DI)
- inability to concentrate urine
- massive water diuresis
3 things that facilitate absorption by the PT
- subcellular specializations
- secondary structural features
- tertiary structural features
PT erubcellular specializations
- mitochondria rich
- wide range of specialized transporters
PT secondary structural features
-brush border membrane
PT tertiary structural features
- convolutions of early proximal tubule
- proximity of all nephronal segments to the vasa recta
In relation to substances being IN THE URINE, what is the role of filtration, absorption, and secretion?
filtration = input absorption = output secretion = additional input
Why is it important to understand clearance?
- Inulin/creatinine clearance measures GFR
- Regular GFR monitoring can help time when dialysis is NECESSARY
- Chronic kidney dz is not curable
Why is knowledge of renal functions essential and critical ?
For safe and proper drug dosage
What is PAH?
para-aminohippurate
What is PAH a useful indicator of?
renal plasma flow (RPF)
In a healthy individual, with normal plasma glucose levels, how much of the glucose is reabsorbed in the PT?
100%
How can glucose end up in the urine?
When the level of plasma glucose exceeds the PT glucose transport maximum (Tm)
How the medullary interstitial hypertonicity generated?
- Active NaCl absorption by TALH
* role of urea recycling
How is the medullary interstitial hypertonicity maintained?
differential NaCl and H2O permeabilities of all segments of the Loop of Henle
Thin descending limb (DTL)
- H2O permeable
- NOT NaCl permeable
Thick ascending limb (TALH)
- ACTIVE NaCl transport
- NOT H2O permeable
Thin ascending limb (ATL)
- PASSIVE NaCl transport
- NOT H2O permeable
- UREA SECRETION
Where does urea secretion occur?
thin ascending limb
Medullary Collecting Duct
- REGULAR permeability to NaCl and H2O
- UREA REABSORPTION
Where does urea reabsorption occur?
medullary collecting duct
What maintains the vertical gradient in the medullary interstitium?
countercurrent exchange between the descending and ascending vasa recta
T/F: Vasa recta are not freely permeable to both NaCl and H2O
False.
They are freely permeable to both NaCl and H2O.
What is the importance of medullary interstital hypertonicity?
required for urine concentration
Urea (7 things)
- small
- highly polar
- protein metabolite
- highly H2O soluble
- freely filtered
- major product for removal of free ammonia in vivo
- contributes to medullary hypertonicity
Can urea pass through pure lipid bilayers?
No; needs urea transporters
Urea transports in the ATL do what?
mediate secretion
Urea transports in the IMCD do what?
fascilitate reabsorption
IMCD stands for?
Inner Medullary Collecting Duct
ADH
Anti-diuretic Hormone
Effect of ADH
- induction of thrist
- pressor effects = aid in maintaining perfusion during vol. depletion
T/F: A change in osmolarity will overrule a change in blood vol.
True.
Primary action of ADH in kidney?
increase H2O permeability of cells in the CD
Ultimately leads to H2O reabsorption and excretion of concentrated urine
How does ADH also increase urea recycling?
promoting urea transport in CD
Disruptions to ADH reaching its target cells?
nephrogenic DI
Diuresis
- removal of ADH leads to endocytosis of AQP2 from apical membrane
- decreases H2O permeability of CD, therefor decreases reclamation of H2O from urine
- excreted urine is therefore very dilute
Central diabetes insipidus
- ADH RELEASE is impaired
- defect is at the SOURCE
Nephrogenic diabetes insipidus
- ADH SIGNALING is impaired
- defect is at the TARGET
Why do you perform a water deprivation test?
H2O deprivation should stimulate an ADH response and increase H2O reabsorption (concentrate urine) in ANY non-DI subject
Why do you perform an ADH Response Test?
Administration of ADH should increase H2O reabsorption in non-DI AND CENTRAL DI subjects, but NOT in nephrogenic DI subject
What is the outcome for both water deprivation test and ADH Response Test?
increase in urine specific gravity for positive response
Who should not increase H2O absorption with a dose of ADH?
nephrogenic DI subjects
T/F: The concentration of Na+ in the ECF is a good indicator of ECF volume.
False.
[Na+] in ECF is not a good indicator of ECF volume.
Aldosterone
- released by zona glomerulosa cells of adrenal cortex
- stimulated by angiotensin II
- also stimulated by elevated plasma K+ and ACTH
What is ACTH?
adrenalcoricotrophic hormone
stress increases this one
How does aldosterone relate to Na+ absorption?
increases sodium absorption from luminal fluid in CD
This causes Na+ to be retained
T/F: Increased Na+ intake decreases aldosterone synthesis
True
Amiloride
- binds to apically located ENaC
- blocks Na+ conduction by that protein = INHIBITS Na+ REABSORPTION
What increases the production of epithelial sodium channels (ENaC)?
aldosterone
