Renal Physiology Flashcards
___% of bwt is ICF
40%
___% of bwt is ECF
20%
___% of bwt is plasma (____% of ECF)
4-5%; 20%
which of the following does not contribute to ECF water balance
- drinking
- saliva
- metabolic water
- sweating and panting
- renal free water loss (regulated by ADH)
- obligatory renal losses
metabolic water (contributes to ICF)
animals require ___ mL of water per 1 kCal energy
1 mL
T/F large animals require relatively more water than small animals
F; caloric intake is a log function of BW
what are the three pathways for water movement
lipid pathway (simple diffusion); water channels (aquaporins); pores/intercellular gaps (glomerulus)
osmotic pressure
the hydrostatic pressure required to oppose the movement of water through a semi-permeable membrane in response to an osmotic gradient
osmotic gradient
the difference in particle concentrations on 2 sides of a membrane
osmolarity
the concentration of solutes in solution that exert osmotic force (includes both those that can readily cross a membrane and those that cannot)
osmolarity is measured in solute/____ whereas osmolality is measured in solute/___
osmolarity: solute/L of water; osmolality: solute/kg of water
tonicity
the concentration of solutes that cannot readily cross membranes, and thus influence water movement
T/F fluid moves across a membrane until the tonicities are the same
T
what determines osmolarity in the ECF? What is the MAIN one
glucose, anions (Cl, HCO3), sodium; Na
what determines osmolarity in the ICF? what is the MAIN one
potassium and anions (Cl, HCO3); K
what is the major determinant of extracellular fluid volume
sodium
T/F intracellular fluid regulation relies on passive movement of K through leaky channels in response to the Na concentration in the ECF
T
what balances ion concentrations via several complex mechanisms
the renal system
the sum of the osmotic effects of ions, plus the oncotic effects of proteins, leads to an effective plasma osmolarity of approximately…
300 mOsm/L
what three forces balance fluid distribution between ICF/ECF
osmotic, oncotic and physical forces
When there is only FLUID LOSS, what happens to ICF and ECF compartments
losses are equally shared
When there is ION LOSS, what happens to ICF and ECF compartments
fluid balance becomes disturbed because the body can not longer move fluids osmotically
What disturbances cause edema and effusions
Changes in plasma protein level or capillary pressure
Dehydration
lack of sufficient body fluid
What tests are used to initially assess dehydration
Skin tent and mucous membranes
What non-specific signs can indicate dehydration
tachycardia, sunken eyes, delayed CRT, hypotension
What laboratory signs indicate dehydration
PCV and TP increased
T/F change in BW over the course of time in hospital will reflect changes in hydration
T
provided kidneys are functional, urine production should ________ fluid intake
=
How is dehydration expressed clinically
% loss in BW
What is a balanced vs unbalanced solution
Balanced has same ion concentrations as ECF (no movement); unbalanced has different ion concentrations from ECF
What are crystalloids
Solutions containing ions and solutes that can move freely between different compartments (ex. between ICF and ECF)
What are colloids
Solutions containing larger molecules that cannot leave plasma and therefore exert an osmotic effect to maintain the volume of fluid in the vascular space
If an animal is in shock, you want to give them _______
colloids (ex. dextrans and hetastarch)
isotonic solutions effect
increase ECF; no change in ICF
hypotonic solutions effect
decreases ECF osmolarity; net increase in both ECF and ICF
hypertonic solutions effect
huge increase in ECF osmolarity; increase in ECF and decrease in ICF
0.9% NaCl, plasmalyte A/148 and LRS
isotonic solutions (will increase ECF)
0.45% NaCl
hypotonic solution (will increase ECF and ICF)
7.5% NaCl
hypertonic solution (will increase ECF and decrease ICF)
BUN is a product of ____________ metabolism
amino acid
Cr and SDMA are products of __________ metabolism
muscle and cellular
T/F ketones and sulphates are reabsorbed in the kidney
F; they get excreted
What are the endocrine functions of the kidney
RAAS; EPO production (regulates RBC production); vitamin D metabolism (converts 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3)
what are the 3 functions of the kidney
excretion of waste (nitrogenous, toxins, drugs), endocrine, regulate ECF volume and bp
what are the vascular components of the kidney
glomerulus, afferent arteriole, efferent arteriole, glomerular capillaries, peritubular capillary, vasa recta
what are the tubular components of the kidney
bowman capsule, proximal convoluted tubule, loop of henle, distal convoluted tubule, collecting tubule/duct
what does the juxtaglomerular apparatus consist of
afferent/efferent arterioles, macula densa, juxtaglomerular cells, mesangial cells
the juxtaglomerular apparatus is responsible for
renin release
what is the macula densa
specialized portion of distal tubular epithelial cells that are adjacent to the JG cells
juxtaglomerular cells lie between
the afferent arteriole and the distal convoluted tubule
the JG apparatus is important for (2)
local regulation of GFR and systemic bp regulation
T/F the glomerulus, under normal conditions, allows complete retention of plasma proteins
T
why is GFR important
it is maintained in the normal kidney, determining GFR is a key step is assessing renal function clinically
GFR is _______ correlated with body size
inversely
what is the size cutoff for GFR
small molecules <2nm pass; molecules >4nm retained
what contributes to the filter membrane of the glomerulus
fenestrated endothelium, glomerular BM, podocytes
what about molecules that are 2-4nm
variable filtration, depending on electrical charge and deformability
T/F -ve charged proteins tend to flow more easily
F; + flow more easily, - tend to be retained
what molecules must be absorbed from glomerular filtrate
Na, K, Cl, HCO3, glucose
glomerulonephritis is associated with
protein-losing nephropathy; immune-mediated
what facors influence GFR
- renal blood flow (RBF)
- renal perfusion pressure (PGC)
- surface area
- ultrafiltration coefficient (KUF)
- balance of P and π in capillaries and tubule lumen
Increased resistance in the afferent arteriole has what effect on GFR, RBF and PGC
dec GFR, dec RBF, dec PGC
Increased resistance in the efferent arteriole has what effect on GFR, RBF and PGC
inc GFR, dec RBF, inc PGC
Decreased resistance in the afferent arteriole has what effect on GFR, RBF and PGC
inc GFR; inc RBF, inc PGC
Decreased resistance in the efferent arteriole has what effect on GFR and RBF, and PGC
dec GFR; inc RBF, dec PGC
autoregulation maintains a nearly constant GFR at _________ when MAP is between ___________
180L/d; 80-180 mmHg
if you increase pressure in the afferent arteriole, it will
constrict
if you decrease pressure in the afferent arteriole, it will
dilate
what mediates the myogenic response
stretch receptors (open and close ion channels)
what modulates the myogenic response
local factors (ex. prostaglandins, NO)
how do hormones and autonomic neurons contribute to renal autoregulation
change resistance in arterioles; change the filtration coefficient by altering the tension on podocytes
T/F sympathetic stimulation increases renin release (as well as increases vascular resistance)
T
describe RAAS
- JG cells secrete renin when bp drops (stim by sympathetic NS)
- renin converts angiotensinogen to angiotensin I
- in the lungs, angiotensin I converted to angiotensin II by ACE
- angiotensin II directly impacts vasoconstriction
renin comes from the __________ and angiotensinogen comes from the ________
kidney; liver
what stimulates the release of renin (what state of the body)
by an decrease in bp
angiotensin II, in addition to causing vasoconstriction in the kidney, causes what endocrine effects (2)
- stimulates release of aldosterone from the adrenal cortex (regulates fluid volume)
- stimulates release of ADH from the posterior pituitary (regulates osmolarity)
macula densa senses increased bf as
increased NaCl
describe tubuloglomerular feedback
increased GFR -> increased tubular flow rate -> increased NaCl detected by macula densa -> macula densa releases adenosine -> adenosine detected by afferent arteriole -> afferent constricts -> increased resistance in afferent arteriole -> GFR decreases
what is a consequence of high sodium in the diet
decreases GFR via tubuloglomerular feedback, which worsens kidney function
T/F Tubuloglomerular feedback inhibits renin secretion
T
hydrostatic pressure in the glomerular capillary is maintained at ______ due to autoregulatory pathways for GFR
50-60 mmHg
what is the effect of reduced renal perfusion pressure on autoregulation
- decrease in myogenic reflex and TGF - > decreases resistance in afferent A
- increase in angiotensin II -> increased resistance in efferent A
what is the effect of increased renal perfusion pressure on autoregulation
- increased myogenic reflex and TGF -> increased resistance in afferent A
- decreased angiotensin II -> decreased resistance in efferent A
You can determine GFR by measuring the 1) concentration of a substance in blood 2) concentration in the urine, and 3) the volume of the urine, as long as the substance is
filtered and not reabsorbed/secreted
what are two classic substances used to measure filtration and a more recent marker
inulin and creatinine; SDMA
how is glomerular function assessed in general practice
by seeing if creatinine falls in the normal serum range; if filtration is impaired, creatinine will rise in the blood
an increase in creatinine, urea, SDMA and other nitrogenous waste in blood is called
azotemia
azotemia can be (3), give an example of each
prerenal (not enough bloodflow ex. dehydration)
renal (dec # of functioning glomeruli or impaired glomerular function, ex. lepto)
postrenal (distal to the kidney, ex. urolith or bladder rupture)
what is uremia
the clinical signs associated with renal failure and increased BUN/creatinine
to examine if the glomeruli is leaky, look for ________ in the _________; to examine if the glomeruli are filtering enough (GFR), look for __________ in the _________
protein; urine; BUN/creatinine/SDMA; blood
leaky glomeruli cause ________ whereas not enough filtration causes ________
proteinuria; azotemia
the effectiveness of reabsorption is reflected in the _________ and ___________ of urine
volume; specific gravity (ion concentration)
T/F secretion occurs in the loop of Henle
F
What is reabsorbed in the proximal tubule (PCT)
- NaCl (60%)
- water (60%)
- bicarb (60-85%)
- glucose (100%)
- AA (100%)
What is secreted in the proximal tubule
creatinine (why it isn’t a perfect maker of glomerular filtration)
90-95% of water absorption is
transcellular
what type of transport requires favorable electrochemical gradients
paracellular
what is reabsorbed via solvent drag
Mg, P, Ca
diuretics tend to target
reabsorption of Na (block this so that water is also not reabsorbed)
what is the principle driver of reabsorption
Na/K ATPase
how is Cl reabsorbed
paracellular: diffusion with Na
transcellular: Cl/anion exchange; Cl channels at basolateral membrane
how is HCO3 ultimately reabsorbed
via Na/HCO3 cotransport
how is glucose reabsorbed
- Na/glucose/AA symport
2/ GLUT1/GLUT2 on basolateral membrane
what is the glucose threshold
10 mmol/L
where are many organic ions, drugs and toxins excreted
PCT
describe the limbs of the loop of henle
thin descending, thin ascending, thick ascending
the descending limb is permeable to ________ and less permeable to _________
water; NaCl
what occurs in the thin ascending limb
a small amount of NaCl is reabsorbed by diffusion
the thick ascending limb is permeable to ___________ and impermeable to __________
K, Cl, Na (via active reabsorption); water
what is the cotransporter for Na, Cl, and K called and where is it
NKCC2; in thick ascending limb of the loop of henle
what is the osmolarity of the fluid by the end of the loop of henle? what about the interstitium at the same spot?
100 mM (very dilute); 300 mM
what happens to salt removed from the fluid
carried to the medulla by the vasa recta (>1000 mM near the deepest part of the medulla)
what is reabsorbed in the distal tubule and how
NaCl; via Na/Cl cotransport and followed by Na/K ATPase and a Cl channel
the distal tubule is (permeable/impermeable) to water
impermeable (further decreases osmolarity in the tubular fluid)
what is reabsorbed in the collecting duct and how
last bit of Na and Cl; Na passively through an Na channel (exits via Na/K ATPase); Cl through paracellular diffusion
what 3 processes are required to dilute urine
- hypertonic medullary interstitium via countercurrent multiplier
- dilution of tubular fluid in the thick ascending loop (via reabsorption of NaCl but not H2O)
- selective water permeability of the CD mediated by ADH
how does aldosterone help dilute urine
reabsorption of Na in the DCT
1.008-1.012 is
isosthenuria
> 1.030 in dogs and >1.040 in cats is
hypersthenuria
<1.008 is
hyposthenuria
if the animal is dehydrated and the urine is 1.008-1.012, then this suggests (2)
- the kidneys aren’t working properly
- ADH-hyposecretion
what happens to K after a meal
loaded into ICF in cells, which acts as a pool for slow release and eventual excretion by the kidneys
what moves K into cells
insulin, E and aldosterone
K reabsorption occurs
70% in PT
20% in ascending LH
K secretion occurs
DT/CD
T/F aldosterone increases K reabsorption
F
T/F increased tubular flow increases K secrettion
T
T/F most filtered Mg is excreted
T
T/F creatinine is only released during skeletal muscle damage
F; it is released normally at a relatively fixed rate
when muscle is damaged, what is released
creatine kinase (CK); biomarker
creatinine is a _________ of _________ metabolism, produced at a ___________ rate.
byproduct; muscle; constant
how is ammonia produced
by glutamate dehydrogenase from glutamate or glutamine
ammonia is used to synthesize ________ in carnivores/most domestic animals and _________ in birds/reptiles
urea; uric acid
how is urea synthesized (what cycle)
Krebs
where is the only site with all 5 enzymes for urea synthesis
liver
what are the main AA in the urea cycle
glutamate, aspartate, arginine
of the 5 enzymes used to synthesize urea, where are they located
2 in mitochondria, 3 in cytosol
the urea cycle enzymes ____ with low protein diets and ____ with high protein diets; they also ____ during starvation due to ____ AA catabolism
decrease; increase; increase; increased
T/F Na, K and Cl all contribute to urine specific gravity and are therefore measured indirectly during urinalysis
T
T/F it is normal if urine becomes cloudly on standing or refrigeration
T
a normal urine pH in carnivores is _______ and herbivores is _________
acidic; alkaline
T/F hyaline, granular casts at low levels are normal
T
T/F cellular casts are normal
F
T/F a small number of cells and bacteria is normal
T
what is glomerulotubular balance (GTB)
ability of each segment of the proximal tubule to reabsorb a constant fraction of the glomerular filtrate; if high Na, blood flow increases, proximal tubule reabsorbs relatively less Na, more Na/water passes in urine, normalization of blood volume
what is pressure natriuresis
pressure changes in the kidney vasculature directly alter Na excretion
what triggers aldosterone release
ang II, ACTH, and hyperkalemia
