7 - renal physiology Flashcards
renal blood flow - % CO
20-25% cardiac output (1.2L/min)
renal blood flow - regulated by
renal vascular resistance
what is renal plasma flow
RPF = RBF x (1-hct). More concentrated blood has lower RPF
para-aminohippuric acid is what
used to measure RPF
nl RPF #?
670
filtration fraction def
blood actually filtered by glomerulus
filtration fraction - RBF and RPF
10% RBF and 20% RPF (80% unfiltered)
what happens to unfiltered renal plasma flow
leaves glomerulus via efferent arterioles to become peritubular circulation
2 types of nephrons and main diff
cortical (short tubule) and juxtamedullary (long tubule) nephron
2 types of nephrons and % of all nephrons
cortical (85%) and juxtamedullary (15%) nephron
loop of henley - which side is thick/thin
descending - thin, ascending - thick
how is net filtration pressure for glomerulus calculated
net filtration pressure = glomerular hydrostatic pressure (55mmhg) - colloid osmotic pressure (30 mmg ) - capsular hydrostatic pressure
what is net filtration pressure #?
10-15mmhg
what is def of renal clearance (creatinine)
volume of plasma cleared of a substance in a specific time (cc/minute)
nl creatinine clearance
1mg/kg/hr or 1 mg/min
by what % does creatinine overestimate GFR
15-20%
what is nl decline in GFR with age
7cc/min/decade
prox tubule - % na reabsorbed
70%
thin descending loop - % na reabsorbed
0 - permeable to water only
thin limb - effect of permeability
increased concentration
thick ascending loop - % na reabsorbed
20%
2 things that augment sodium reabsorbtion in thick ascendin limb
aldosterone and ADH
thick ascending loop permeable to?
solutes, not water
thick ascending loop works how?
sodium pumped out, resulting in hypotonic fluid at end of tubule
distal convoluted tubule - % na reabsorbed
10%
primary driver of reabsorbtion in PCT
Na-K ATPase pump out
primary driver of reabsorbtion in PCT - why
secondary active transport and passive reabsorbtion are dependent on co-transport of sodium in or ion gradient, respectively
what is secondary active transport
absorbtion of things co transported with sodium
what is passive reabsorbtion
negatively charged ions travel along electrical gradient created by na active transport
concentration gradient in kidney
300-1200
what type of nephrons are involved in countercurrent mech
juxtamedullary nephrons
what is countercurrent mech
interraction btw filtrate flow through loop of henle of JG nephrons and blood flow through vasa recta
how is na reabsorbed in PCT - 2
NA-H and Na-solute active transporters
glucose reabsorbtion in PCT
100% reabsorbed in PCT via na-gucose co-transporter
HCO3 and prox tubule
generated in cell and absorbed with sodium
aa, peptides, vitamins in PCT
90% reabs via 2ndary active transport w na
cations in PCT
passive transport along e-gradient
anions in PCT
passive transport along e-gradient for cl- and 2ndary transport w na
H2O in PCT
osmotically driven, aquaporins
where is ca reabsorbed
prox and distal tubules
where does PTH have effect on ca
DCT
where does aldosterone have effect
DCT and collecting duct
reabsorbtion via primary active transport in collecting duct
primary active transport by na, regulated by aldosterone, and medullary gradient allows for passive transport of cl- and HCO2 for reabsorbtion
where is ammonia secreted
PCT
how is NH4+ reabsorbed
NH3- secreted into lumen, traps H+
where is tubular secretion most active
PCT (also happens in DCT and collecting duct)
what gets secreted in collecting duct and what stimulates it - 3
K by aldosterone, NH3 to trap H+, and H based on blood pH
how to make dilute urine
ascending loop filtrate is allowed to pass to renal pelvis with no modification. Passive
how to make concentrated urine
ADH - makes collecting ducts permeable to water and increases water uptake from urine.
where is ADH made
hypothalamus
where is ADH stored
posterior pituitary
ADH secondary effect
makes collecting ducts more permeable to urea, promoting concentration gradient in inner medulla
atrial natiuretic peptide effect on urine
makes dilute urine
atrial natiuretic peptide effect on kidney
vasodilation of afferent arterioles –> inc GFR –> more na reaches macula densa and ANP opposes RAS therefore naturesis (loss of na)
ANP made/stored/released where
atrial myocytes in response to stretch (HTN, hypervolemia)
osmotic substances and diuresis
osmotic substances inc osmolality and hold water in filtrate
loop diuretics MOA
inhibit na/k/cl cotransporter on lumina membrane of thisk ascending loop of henle, reducing medullary solute content and impair urinary concentrating ability.
loop diuretics increase excretion of what 5 electrolytes
na, k, cl, ca, mg
thiazide MOA
inhibit na-cl exchanger in DISTAL convoluted tubule. More na in filtrate and more water excreted
thiazide effect on electrolites
decreaed serum [na/k], increased serum [ca]
kidney role in acid-base balance - 2
excrete non-volatile acids (lungs excrete volatile acids (esp CO2)), and reabsorb all HCO3
net effect of metabolism is to create
acid
nl urine pH
6
blood [HCO3-]
24 mM
blood PCO2
40 mmHg
anion gap calc
na-[cl+HCO3-]
nl anion gap
(10-12)
sources of net H+ gain - 4
CO2, nonvolatile acids (lcatic acid), loss of HCO3- in diarrhea, loss of HCO3- in urine
sources of net H+ loss - 4
loss in urine, loss in GI secretions, hyperventilation (blow off CO2), use of H+ in metabolism of organic anions
how do kidneys affect serum [H+]
by altering [HCO3-]
nl % HCO# reabsorbed
100%
how is HCO3- reabsorbed
HCO3- + H+ -(CA 1)-> CO2 + H2O - (CA2) –> HCO3- (to plasma) + H+ (back to tubule). CA= carbonic anhydrase
how to add HCO3 to serum
H+ combines with phosphate in tubule, CA2 still makes HCO3 from CO2 and H2O
metabolic acidosis - compensation
hyperventilation
metabolic alkalosis - compensation
hypoventilation
respiratory acidosis - compensation
renal HCO3- reabsorbtion
respiratory alkalosis - compensation
renal HCO3- excretion
3 hormone functions of kidney
erythropoetin, vit D ACTIVATION, endothelin production
where in kidney erythropoetin made
interstitial cells in kidney
what stimulates erythropoetin release
hypoxia and anemia
vit D as it passes through kidney
25-vit D –> 1,25 vit D
what are endothelins
made by kidney - work in vasoconstriction and salt retention. Functionally similar to RAS
def of renovascular disease
renin dependent HTN cured by correction of renal vasc HTN
nephrosclerosis
microvascular dz of kidney
% with refractory HTN who have RAS
3%
3 main categories of RAS
atherosclerosis, fibromuscular, secondary lesinos
% RAS lesions atherosclerosis
70%
% RAS lesions fibromuscular disease
20%
3 types of fibromuscular dysplasia
intimal, fibromuscular, perimedial
who gets intimal hyperplasia
kids < 18 yo
intimal hyperplasia characterized by
collagen inside elastic membrane
how does perimedial fibroplasia happen
collagen deposition in outer media within external elastica
what does perimedial fibropalsia angiogram look like
beaded with COLLATERALS
intimal hyperplasia on angiogram
smooth focal stenosis
what makes medial fibroplasia different
non-progressive.
medial fibroplasia on angiogram
string of beads
who is at risk of aneurysm rupture
women of child bearing age
what size aneurisms rupture
> 2-3 cm (la place law - wall tension is function of radius)
type of aneurism that is at higher risk of rupture
saccular
pathophys of ischemic renal artery disease
juxtaglomerular aparatus responds to decreased blood flow and low [sodium] (macula densa cells) releases renin –> inc BP, inc Na retention
what % stenosis is clinically significant
70% (bernuli principle - 70% decrease in diameter = 50% flow decrease)
where are macula densa
distal tubule
what does macula densa do
senses BP and releases renin when increased BP
path of RAS
angiotensinogen (liver) -(renin)-> angiotensin 1 -(ACE in lung)-> angiotensin 2
effects of angiotensin 2 (5)
inc central symp activity, tubular nacl retention K excretion, aldosterone release (hold nacl, release k), arterial constriction, ADH secretion (H2O absorbtion)
receptor for angiotensin 2
AT1
net effect of angiotensin 2
inc intracellular Ca –> vasocontriction and aldosterone adrenal
AT1 antagonists
sartans (ARB’s)
how does angiotensin affect GFR
constricts efferent arteriole to maintain hydrostatic pressure
ACE inhibitor in RAS
cr goes up because decreased hydrostatic pressure
clinical char of renal vasc HTN (5)
- abrupt onset HTN < 30 yo (fibromuscular lesions) or > 50 yo (atherosclerosis), 2. severe/refractory HTN, 3. HTN < 2 yrs, 4. hypokalemia, 5. progressive azotemia w meds for HTN
when does captopril renogram not work
GFR < 50
best imaging study for RAS
duplex renal us - only detects > 60% stenosis. Cant quantify stenosis. CT/MRA not sensitive enough
criteria for renal salvage in ischemic nephropathy - 4
kidney > 9 cm, function on mag 3, cr < 30, 50% glomerulosclerosis on biopsy
principles to limit morbidity in surgery for surgical correction of RAS - 2
avoid badly diseased aorta’s, correct extra-renal vasc disease prior to renal surg
when is nephrectomy best choicefor RAS- 6
- branch disease/ occlusion/Infarction, 2. severe atrophy < 9 cm, 3.segmental hypoplasia, 4. non correctable lesions, 5. failed prior revasc, 6. good contralat function
best surgical correction for RAS
aortorenal bypass
surgery vs angioplasty - fibromuscular dz - 5
surgery for failed PTA, branch disease, total occlusion, aneurysms, dissections
surgery vs angioplasty - artherosclerosis
same as fibromuscular including simultaneous aortic repair
what have RCT’s shown for RAS tx
surgery, stents, PTA are no better than medical therapy
contributing factors to kidney concentrating mechanism - 4
- countercurrent multiplier, 2. urea diffussion by DCT, 3. vasa recta cycling salt to inner medulla, 4. aquaporin water channels (ADH)
3 parts to countercurrent mech (concentrating effect of kidney)
H2O diffusion through loop of henle, urea diffusion, vasa recta
loop of henle and counter current mech - AKA
aka countercurrent multiplier
loop of henle and counter current mech - mech
descending thin limb permeable to H2O, [filtrate] increases as H2O reabsorbed. Thick ascending limb permeable to solutes, not H2O
urea diffusion and countercurrent mech
deep medullary gradient bolstered by passive diffusion of urea through colelcting duct
vasa recta and countercurrent mech
facilitate [gradient] by cycling salt to inner medulla via efferents and out
hyponatremia usu results from what defect
renal water handling
primary defect in hypernatremia
impaired water intake in the setting of increased water loss
why r geriatric pts more at risk of hypernatremia - 2
decreased thirst response and decreased renal concentrating ability
first step when you see metabolic acidosis
calculate anion gap to look for missing anions
cardiac findings in hypokalemia - 4
tachycardia, prolonged QT interval, st depression, u waves
4 medical causes of hyperkalemia
drugs, hyperaldosteronism, chronic acidosis, renal failure
3 drugs causing hyperkalemia
ace inhibitor, K sparing diuretics, beta blockers
3 EKG findings in hyperkalemia
peaked t waves, shortened QT, ST segment depression,
3 signs of advanced hyperkalemia on EKG
widened QRS, increased PR interval, decreased p wave amplitude
when is calcium gluconate indicated in hyperkalemia
EKG shows signifcant abnormalities (QRS widening, loss of p wave, arrythmia)
high sodium concentration sx - 4
lethargy, weakness, irritability, twitching
low calcium sx - 4
tetany, depression, papilledema, seizures
high calcium sx - 3
abd pain, constipation, fatigue
low mg - 5
weakness, anorexia, tetany, delrium, coma
high phos sx - 3
tumor lysis syndrome, rhabdo, renal failure
where is calcium absorbed
majority in PCT and ascending loop, fine tuning (15%) in DCT and collecting duct
primary defect in RTA type 1
failure of H+ secretion in distal nephron
ammonium chloride test
provocative test for RTA type 1
RTA type 2 defect
failure of BICARB reabsorbtion in PCT
RTA type 2 finding
kid with growth retardation and metabolic bone disease (tiny tim)
2 ways to treat alkalosis with gastric substitution
PPI and acidificaiton with dilute HCL solution
metabolic problem in addition to K, Cl in jejunum
HYPOnatremia
treatment for jejunal metabolic abnormalities
nacl tabs, thiazide
why do ppl have acidois with ileum
inability to secrete acid as ammonium (reabsorbed) depeltes buffers
what happens with B12 deficiency
anemia and neurologic degeneration
why does postobstructive diuresis happen
urea is osmotic diuretic - loss of concentrating ability from urea washout from medulla
renal duplex criteria for renal vascular HTN
peak systolic velocity > 1.8 cm/sec = > 60% stenosis
renal vascular disease 1 kidney 1 clip vs 2 kidney 1 clip and plasma renin activity
1 kidney 1 clip = bilateral RAS and unchanged plasma renin activity, however na retained due to low perfusion pressure and water retention/HTN occurs. 2 kidney 1 clip - stenotic kidney rleases renin to increase perfusion pressure, resulting in ACE responsive HTN with nl bloodvolume
renal us resistive index prognostic significance
if > 0.8 then revascularization unlikely to help renal function
where is renal artery angioplasty helpful
fibromuscular dysplasia
2 groups who get renal artery senosis surgical repair
- surgical aortic repair, 2. pts with renal artery aneurism (@ risk for rupture, > 2 cm, no calcifications, expanding, HTN, pregnancy)
renal fuction after surgical/endovascular renal artery repair
no change usually
signs of RAS reversibility with stenting
progressive occlsion, collaterals, retrograde arterial filling, size > 7 cm, cr < 4, preservation of glomeruli on biopsy
