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Renal Physiology
overview of several lectures on renal physio
96
Physiology
Professional
04/18/2011

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Term
role of kidneys
Definition
maintain serum composition, retain water, regulate osmotic pressure of body fluids, eliminate waste products/foreign compounds, regulate extracellular fluid volume, regulate arterial blood pressure, perform gluconeogenesis in prolonged starvation, degrade polypeptide hormones, and synthesize ammonia
Term
kidneys make:
Definition
erythropoietin, calcitriol, prostaglandins, thromboxane, renin, and kallikrein
Term
erythropoietin
Definition
stimulated by hypoxia, produced by renal cortex, stimulates production of erythrocytes and increases oxygen carrying capacity of blood
Term
anemia in chronic liver failure
Definition
due to deficiency of erythropoietin production
Term
calcitriol
Definition
produced by kidneys in response to decreased plasma calcium, also written as 1,25-OH2 vit D3, increases intestinal calcium absorption, promotes PTH action, and increases plasma calcium
Term
chronic renal failure
Definition
associated problems include calcium malabsorption, hyperparathyroidism, bone disease, and vascular calcification; results in decreased renal tubular mass, decreases 1-25-OH2 vit D3 synthesis
Term
prostaglandins and thromboxanes
Definition
modify inflammatory responses, formed from arachidonic acid by COX1 and 2 in the kidney, increase renal blood flow/Na excretion/renin release, and inhibit ADH action
Term
ACE II inhibitors
Definition
block synthesis of Angiotensin II and treat hypertension
Term
kallikrein
Definition
converts kininogens to active kinins, which are potent vasodilators, produced by kidney
Term
nephron
Definition
basic unit of kidney, approximately 1.2 million per kidney, several of them feed into one collecting duct, surrounded by capillaries, made up of glomerulus/proximal and distal tubules/collecting ducts
Term
vasa recta
Definition
blood vessels descending into the medulla from the efferent arterioles, follow loop of Henle
Term
main driving force of filtration
Definition
hydrostatic pressure in glomerular capillaries
Term
blood flow to kidneys
Definition
very high, approximately 25% of cardiac output, sustains high rate of plasma filtration and explains why kidney is important in regulating ECF volume/composition
Term
proximal tubule
Definition
specialized region of nephron for reabsorption/secretion, has a large surface area/large # of mitochondria/leaky tight junctions, moves sodium to the basolateral side by pumps
Term
juxtaglomerular apparatus
Definition
composed of macula densa, granular cells, and extraglomerular mesangial cells; responsible for renin release and tubuloglomerular feedback
Term
fluid flow past MD decreases
Definition
JGA releases renin, angiotensin II is produced, and systemic vasoconstriction occurs; filtration and fluid flow past glomerulus ultimately increases
Term
fluid flow past MD increases
Definition
JGA reduces GFR (via local ATP/adenosine action), tubuloglomerular feedback occurs
Term
decreased NaCl at MD
Definition
increase in prostaglandin in interstitium of JGA, PGE2 binds to EP4 (receptor)/stimulates renin release from granular cells
Term
low concentration of AngII
Definition
efferent arteriole primarily constricted, renal blood flow decreases but GFR increases due to hydrostatic pressure in glomerular capillaries
Term
high concentration of AngII
Definition
occurs during hemorrhage, both afferent and efferent arterioles are constricted to decrease both GFR and renal blood flow
Term
micturition
Definition
periodic emptying of urinary bladder, 150-250mL causes sensation of fullness, ureters maintain urine flow in one direction
Term
hydrostatic pressure from outside glomerular capillaries
Definition
acts to push fluid back into glomerulus, very small (15mmHg)
Term
protein osmotic pressure
Definition
AKA colloid osmotic pressure, acts to push fluid back into the glomerulus
Term
renal plasma clearance
Definition
mL plasma/min that are cleared of a substance to supply the quantity of the substance in the urine in one minute's time, so = urine concentration*flow rate/plasma concentration
Term
GFR
Definition
=clearance rate of inulin, decreases with age, increases in females, approximately 180 L/day in healthy individual
Term
plasma creatinine concentration
Definition
correlates with GFR, doubling signals loss of 25% renal function (filtration)
Term
filtration fraction
Definition
=GFR/renal plasma flow, approximately 20%
Term
renal plasma flow
Definition
= p-aminohippurate clearance
Term
renal blood flow
Definition
= RPF/ (1-hematocrit), determines how much blood enters the kidney per minute
Term
oxygen usage in kidney
Definition
used to drive sodium reabsorption, extraction LOW from arterial blood
Term
blood flow rate in kidney
Definition
high in cortex to allow high rate of filtration and low in medulla to avoid solute washout
Term
autoregulation of RBF and GFR
Definition
intrinsic property of kidney, minimizes impact of changes in mean arterial BP on GFR, overpowered by sympathetic nervous system during hemorrhage
Term
myogenic mechanism of autoregulation
Definition
changes in BP compensated by changes in vascular resistance; ex: increased BP leads to smooth muscle depolarizing in cortical arteries and afferent arterioles, causes increase in vascular resistance
Term
autoregulation by TG feedback
Definition
only in kidney, does not involve renin-angiotensin, negative feedback that prevents excess loss of Na+ in urine when increase in GFR/BP occurs, NaCl detected by macula densa--triggers constriction of afferent arterioles
Term
mechanism of TGF
Definition
ATP released into interstitial fluid of JGA, ATP metabolized into adenosine, then vasoconstriction caused by A1 adenosine receptors in smooth muscle
Term
renal sympathetic nerves
Definition
cause vasoconstriction, emergency function, routes blood to brain/heart, cause renin release, epi and norepi contribute to vasoconstriction
Term
renal vasodilators
Definition
work to increase RBF, ex: prostaglandins, NO, dopamine, atrial natiuretic peptide
Term
renal vasoconstrictors
Definition
work to decrease RBF, ex: Ang II, epinephrine, norepinephrine, thromboxane A2, adenosine
Term
NSAID to volume depleted patient
Definition
very bad idea because it shuts down prostaglandins and reverses life-saving vasoconstriction
Term
prostaglandins on renal vasoconstriction
Definition
act as brakes, counteract increased plasma Ang II and renal sympathetic activity
Term
cell types of glomerulus
Definition
endothelial cells, podocytes, and mesangial cells
Term
hallmark of glomerular disease
Definition
heavy proteinuria due to loss of filtration barriers, causes tubular damage
Term
3 layers of glomerular filtration
Definition
endothelium, basement membrane, and podocyte slit pores...endothelium is not major contributor (has fenestrae and allows everything except RBCs)
Term
nephrin
Definition
integral protein in podocyte slit diaphragm, important barrier to filtration, negative charges play important role
Term
GFR
Definition
determined by Starling forces, = glomerular ultrafiltration coefficient(hydrostatic P in glomerular capillary - hydrostatic P in Bowman's space - colloid osmotic P in GC)
Term
PGC
Definition
hydrostatic pressure in glomerular capillary, depends on arterial BP and resistances of afferent/efferent arterioles
Term
constriction/dilation of arterioles
Definition
primary effect is to alter hydrostatic P in glomerular capillaries
Term
afferent constriction
Definition
reduces hydrostatic P in glomerular capillaries, reduces GBF and GFR
Term
afferent dilation
Definition
increases hydrostatic P in glomerular capillaries, increases GBF and GFR
Term
efferent constriction
Definition
increases P of glomerular capillaries, reduces blood flow out of glomerulus, GFR can either increase or decrease depending on blood flow remaining
Term
efferent dilation
Definition
decreases hydrostatic P in glomerular capillaries, increases GBF, decreases GFR
Term
hydrostatic P in Bowman's space
Definition
depends on GFR and downstream resistance, responds to tubular obstruction, will cause GFR to fall if it increases
Term
colloid osmotic P in capillaries
Definition
decrease (ex: following isotonic saline infusion) causes increase in GFR
Term
glomerular blood flow's impact on COP
Definition
when very low, the volume of filtrate is small and COP rises sharply, thus ceasing filtration along remainder of capillary; when high, rise in COP is minimal and filtration is sustained along capillary
Term
magnitude of GFR
Definition
constant from birth to 45-50, then declines around 30-40%, important marker of renal function
Term
net reabsorption
Definition
calculated by filtered load - (urine flow rate*concentration in urine)
Term
fractional excretion
Definition
indicates whether substance is reabsorbed or secreted, determined by urinary excretion / filtered load --nearly 100% for inulin and zero for glucose
Term
calculation of net secretion
Definition
equals (concentration in urine * flow rate) - (plasma concentration * GFR)
Term
splay
Definition
caused by nephrons having different carrying capacities of substances
Term
reabsorption of glucose
Definition
occurs in renal proximal tubule, electrochemical gradient helps movement in, co-transported w/ sodium, actively transported into peritubular capillary
Term
reabsorption of water
Definition
approximately 50% halfway across proximal tubule
Term
proximal tubular fluid
Definition
essentially iso-osmotic to plasma, reflects high water permeability, small gradient drives reabsorption of water
Term
diabetes insipidus
Definition
disorder in which water is not reabsorbed due to faulty aquaporins, result is very dilute urine
Term
reabsorption in proximal convoluted tubule
Definition
filtered glucose and AAs almost 100%, filtered Na/water/K at 70%, filtered urea at 50%
Term
secretion at PT
Definition
PAH is cleared completely by this mechanism, others include: carboxylic/sulfonic acids, amines/ammonium compounds, phenol red, penicillin, probenecid, furosemide, acetazolamine, and creatinine
Term
sodium reabsorption
Definition
at PCT, is main driving force for reabsorption of solutes and water, consumes most oxygen and ATP in kidney, always uses Na/K/ATPase, actively transported to interstitial space
Term
organic cations secreted by PTs
Definition
histamine, cimetidine, cisplatin, norepinephrine, quinine, tetraethylammonium, creatinine
Term
lipid soluble organic compound secretion
Definition
undergo non-ionic diffusion, explains use of sodium bicarbonate in sedative overdoses
Term
loop of Henle
Definition
ascending limb is impermeable to water, thick ascending limb absorbs solutes without water (diluting segment), ascending limb increases osmolarity of medullary interstitium
Term
loop diuretics
Definition
ex: furosemide and bumetanide, Na/K/2Cl co-transporter is inhibited on tubular side, allows for less deposition of Na in medullary interstitium and increases water and Na excretion
Term
distal tubule
Definition
consists of convoluted tubule, connecting tubule, and initial cortical collecting duct
Term
distal nephron
Definition
consists of DCT, connecting tubule, cortical collecting duct, outer medulla collecting duct, and inner medulla collecting duct...basically everything beyond the loop
Term
thiazide diuretics
Definition
work on the Na/Cl co-transporter in the luminal cell membrane of the distal convoluted tubule, causes more Na to be delivered to the collecting duct and limiting of reabsorption of water
Term
thiazide diuretics
Definition
block Na/Cl co-transporter in distal convoluted tubule, ex: chlorothiazide and metolazone
Term
collecting tubule
Definition
composed of 2/3rds principal cells and 1/3rd intercalated cells, has tight epithelium, determines final excretion of sodium/potassium/hydrogen, reabsorbs Na through ENaC channels, secretes K, completely impermeable to water
Term
principal cells
Definition
sites of action of aldosterone and ADH, reabsorbs Na and secretes K
Term
intercalated cells
Definition
in collecting duct, important for acid-base homeostasis, alpha type secrete H+/reabsorb K during dietary depletion/predominate during acidosis, beta type secrete bicarbonate and predominate during alkalosis;
Term
AE1
Definition
antiporter that releases bicarbonate into blood in alpha intercalated cells
Term
pendrin
Definition
antiporter that transports bicarbonate into lumen and Cl into cell
Term
renal glucosuria
Definition
caused by defect in SGLT (Na/glucose co-transporter)
Term
cystinuria
Definition
caused by defect in amino acid transporter, damages kidney
Term
Bartter syndrome
Definition
affects Na/K/2Cl co-transporter
Term
Gitelman syndrome
Definition
affects NaCl co-transporter
Term
Liddle syndrome
Definition
affects ENaC channel
Term
nephrogenic syndrome of inappropriate antidiuresis
Definition
caused by increased V2 receptor activity (AQP2)
Term
Starling forces
Definition
control distribution of fluid between plasma and interstitium
Term
result of adding 2.0L pure water
Definition
ICF volume expands w/o proper correction, volume increases while osmolarity decreases
Term
result of adding 2.0L of isotonic saline
Definition
fluid volume expansion stays in ECF, GFR increases to correct it, kidneys will excrete Na and water
Term
result of adding 5% NaCl saline solution
Definition
increase in salt concentration increases ECF volume, increase in osmolarity causes cellular shrinkage, kidneys will correct it with ADH
Term
thirst
Definition
stimulated by cellular dehydration (increased osmolarity of ECF) and fall of ECF volume, mediated by changes sensed by baroreceptors and osmoreceptors
Term
CNS osmoreceptors
Definition
respond to increases in osmolarity, trigger neurons to release AVP and thirst sensation
Term
factors influencing ADH release
Definition
cellular dehydration (increase in effective plasma osmolarity), hypovolemia, a decrease in effective arterial blood volume, pain/trauma/emotional stress/etc., ethanol/atrial natriuretic peptide
Term
swimming's effect on ADH
Definition
action eliminates pooling of blood due to gravity, blood moves to central vessels, increased volume is signaled, causes decrease in ADH and increase urge to urinate
Term
excess hydration
Definition
sensed by cardiovascular stretch receptors and osmoreceptors, which decreases ADH release and less water is reabsorbed; NOTE: reabsorption at PT is not altered
Term
response to dehydration
Definition
body tries to first restore fluid volume by reabsorbing water in collecting ducts and then restore osmolarity by adding Na back
Term
effective arterial blood volume
Definition
is of overriding importance, ex: congestive heart failure signals decreased arterial blood volume and ultimately causes hyponatremia and brain swelling to maintain "normal" blood volume
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