test 4 Flashcards
podocyte
surrounds each capillary through which filtration takes place
mesangial cells
form the mesangium of the glomerulus. change size and contract when they need to filter. Barrier less leaky when contracts, K goes down
what charge passes through glomerulus the best
positive. capillary is negative. so negative is the worst to travel through
glomerulonephritis
inflammation caused by infections. makes glomerular basement membrane lose negative charge so more things will be in the urine.
treatment for glomerulonephritis
steroid therapy
goodpasture’s syndrome
anti-glomerular basement membrane disease. Antibodies develop against the basement membrane causing kidney failure and lung bleeding. symptoms never go away only controlled.
glomerular filtration barrier
- podocytes (epi of bowmans capsule, fenestrated, large poors, neg charge, mensangial cells)
- basement membrane (basal lamina - neg charged, glycoprotiens, coarse sieve)
lies in between - epithelium of Bowman’s capsule (podocytes create filtration slits)
allows 20% plasma to enter bowman’s space
GFR =
GFR= KF [(PGC-PBS)-(πGC- πBS)], GFR is the volume tof plasma that enters bowman’s space, average 125 ml/min (above 100 good), most important regulator is blood flow
PGC: favors filtration, nearly constant
PBS: opposes filtration, constant
πGC: opposes filtration, high conc of protiens causes the rate to dec
πBS: favors filtration, no change because it can’t ever get out of capillaires
what happens to GFR if CO decreases
renal dysfunction will occur because the GFR number will be low
KF
filtration coefficient- how leaky the barrier is. mesangial contract - less leaky, KF Dec
Mesangial relax - more leaky, KF increases
PH - π - Pfluid = net filtration rate
positive to favor filtration
pH- blood pressure
π - proteins in plasma but not in bowman’s capsule
pfluid- created by bowmans’ capsule
efferent arteriole constrict
more volume in glomerulus as less is leaving, higher PH, higher GFR
afferent arteriole constrict
more volume leaving, lower PH, lower GFR
Renal blood flow
approximately 1200 ml/min
kidneys receive 20% of CO, if RBF increases then GFR increases
renal plasma flow (RPF)
= RBF X (1-Hct (%RBC))
what if the RPF is extremely high?
outstrips the filtration capacity of the capillary causing renal dysfunction - kidneys will have too much to handle
solvent movement in kidneys
moves with sodium
Na+ movement
reabsorbed by active transport,
secretion: enters on the luminal side through membrane proteins and moves down the electrochemical gradient
reabsorption: pumped out basolaterial side by the K+/Na+ ATPase
______ drives anion reabsorption
electrochemical gradient
______ drives water movement
osmosis, following solute reabsorption
____ filtrate reabsorbed in PCT
70%
how does reabsorption occur in the PCT
- most reabsorption occurs across the tubular epithelium- transcellular transport
- some reabsorption of water and certain ions occurs between cells - paracellular transport
Main role of PCT
does nothing to produce concentrated urine, just produces a smaller amount of urine - continuously establishes a Na+ gradient so the interior of PCT low Na+, favors primary active transport on the basolateral side of the membrane
penicillin and cimetidine
secreted in PCT
Probenecid and Penicillin
compete for the transporter. only can remove so many molecules. increases concentration of molecules in the body
loop of henle function
concentrating the urine, filtrate becomes larger (1200 millimoles) near the bottom of the loop reaching equilibrium with the interstitial fluid - main goal is to increase the amount of water reabsorbed back by the body without too much energy - uses
descending limb
highly permeable to water not ions. penetrates into the medulla. water moves out into the interestial fluid picked up by the vasa recta. called Thin!, no energy used! makes it hypertonic and passive diffusion because of the electrochemical gradient in the Thick ascending loop
how much filtrate is reabsorbed in the descending limb
15%
Thick Ascending limb
highly permeable to ions, not water. Na+ transported out of the filtrate, diluting it before it reaches the distal tubule. reabsorption of Na, K, Cl, THICK, uses energy to increase the solute concentration in the medulla so water can be reabsorbed in the ascending and collecting duct!
TAL luminal side transporter, how can this be affected by drugs?
1 Na+, 1 K+, 2 Cl = blocked by loop diuretics, filtrate is diluted by removal of ions and no addition of water
countercurrent multiplier
fluid in the medulla can be so high (1200 mOsm)
how does the bloodstream effectively reabsorb all of the water and solutes from the medulla?
promotes movement of water into the capillary lumen because of low hydrostatic pressure and a high protein concentration
vasa recta
capillareis that circulate around the loop of henle. associated with juxtamedullary nephrons. permeable to water and solutes. removes the water after leaving the loop of henle
distal convoluted tubule and collecting ductt
85% filtrate reabsorbed, early DCT impermeable to waste, late DCT and collecting duct may become permeable to water in the presence of ADH.
thiazide diruetic
transporter of the luminal side of the early DCT 1 Na+, 1 Cl- blocked
Loop diuretic
absorbing in the ascending on the luminal side inhibited - makes it so there is low K+ in the plasma (hypokalemia)
lasix
loop diuretic
urea
wate product
dissolved in blood
excreted in urine
regulated by ADH/Vasopressin
handling urea
nephron is impermeable to urea- want to excrete
what is most permeable to urea
papillary duct - goes back into the medulla and contriubtes to the medullary osmotic gradient
faster the urine flow
better the renal function, less urea that is reabsorbed. urea not in papillary duct to be reabsorbed
blood urea nitrogen
indicatory of renal function, if it is too high that means that the kidneys are not functioning well and are reabsorbing a waste product because it is not moving fast enough.
fine tuning GFR
controlled mostly by altering the arteriole diameters - hydrostatic pressure from volume
myogenic response
ability of the afferent arteriole to contract when high pressure - stretched - arteriole pressure stretches due to an increase in perfusion pressure
flow =
(P1 - P2) / resistance
tubular glomerular feedback
afferent arteriole senses the delivery of filtrate to the DCT (macula densa) - increases prostaglandins, dialtes - decreases resistance, decreases afferent arteriole resistance and increase in RPF and GFR
macula densa
sneses volume of filtrate
Renin - Angiotensin - Aldosterone System
RAA - important regulator of renal function and of the CV system. most important regulator of blood volume and blood pressure.
diseases RAA involved with
hypertension, CHF, diabetes mellitus, atherosclerosis, hyperlipidemia
how does RAA maintain GFR
increases PGC, blood pressure, blood volume
aldosterone
increases Na+ and water retention, and increases K+ excretion
what receptor is activated by RAA system
SNS activates systems via B1 receptor stimulation
activation of the RAA system
angiotensin (made in liver) converted by renin (RLS) to angiotensin (10AA) which is converted to angiotensin 2 (8AA) by angiotensin converting enzyme - peptidase located on pulmonary vascular endothelial cells, acts on two receptors AT1R (favored) and AT2R
ACE
luminal side of the pulmonary vascular endothelial cells to convert ang1 to ang2, benefit of it located in the lungs is that is where all of the O2 lives so it can sense the CO changes
ACE inhibitors
blocker of RAA, (“prils”) stops the conversion of ang 2
alskiren
renin inhibitor - stops the conversion to ang 2
AT1R blocker
ang 2 can’t act on
diabetics and RAA
they need to use RAA blockers/inhibitors as they have renal dysfunction
renin release stimuli
decreased flitrate delivery to the macula densa causes renin to be released from the JG cells
decreased filtrate is caused by
total volume in body low, increased urea in plasma decreases the filtrate (flow rate), decreases the pressure/volume
to increase renin release
B1 receptors on the JG cells, TGF works with others, prostaglandins
as arterial pressure goes down,
PGC goes down, GFR goes down, Macula densa delivery goes down, TGF causes the afferent arteriole resistance to go down which has a negative feedback on the PGC
as macula densa goes down also causes the renin levels to go up, ang 2 to go up, and efferent arteriole resistance to go up to have a negative feedback on the PGC
role of TGF
TGF decreases afferent arteriolar resistance by the paracrine release of vasodilatory prostaglandins, such as prostacyclin - causes vasodialation and is a drug.
flolan and remodulin
vasodialation and is a drug
there’s a decreased renal perfusion pressure (renal artery has occlusion so diameter is small) - what would happen if NSAID was administered
First decrease in perfusion pressure - relying on compensating mechanism of the afferent arteriole and releases prostaglandins to try and make the diameter bigger and improve blood flow - NSAID would inhibit this whole process
role of ACE inhibitor (ramipril)
targets the afferent arteriole, increaess GFR pressure - constricts the efferent arteriole to maintain volume. ACE inhibitor decreases ang 2 so you can’t constrict the arteriole as well
lisonopril affect on Renin and K+
renin increase in an effort to increase ang 2, K+ increases
aldosterone
produced in the renal cortex (zona glomerulosa), steroid hormone, highly lipophillic
3 main stimuli for aldosterone secretion
- decrease Na+ concentration in the plasma
- decrease total volume of plasma
- increase plasma concentration of K+
aldosterone acts on the late DCT and collecting duct to cause
increase in Na+ reabsorption, increase in water reabsorption, increase in K+ secretion
aldosterone acting on principle cells
- aldosterone combines with the cytoplasmic receptor
- hormone receptor complex initiates transcription in the nucleus
- translation and protein synthesis make a new protein channels and pumps aldosterone-induced proteins which modulate existing channels - RESULT: increased Na+ reabsorption and K+ secretion - pumps formed by aldosterone to increae K+ and Na+ movement and increase ATPase
aldosterone functions
- increased basolateral Na+/K+ ATPase density and activity
- increased luminal ENaC - epithelial sodium channel
- Increased ATP production within the cell in order to maintain transport activity
spironolactone (aldactone)
aldosterone receptor antagonist for someone with congestive heart failure for effective diuretics - acts early so aldosterone can’t bind to receptor
eplerenone (inspra)
aldosterone receptor antagonist newer drugs, more specific and selective so less adverse events
triameterene (dyrenium)
inhibits ENac channels - further for formation of channels but won’t work the same
amiloride (midamore)
inhibits ENac channels- further for formation of channels but won’t work on the same
weak diruetics
help balance of loosing to much K+ like a regular diuretic - never on monotherapy of one type
amount excreted =
amount filtered - reabsorbed + secreted
inulin clearance
freely filtered at the glomerulus and not secreted or reabsorbed
renal clearance of inulin = GFR
creatnine
produced by the body so better to measure than inulin. 99% filtration 1% reabosorption
Ccr =
excretion rate x volume / plasma concentration
normal GFR
180 L / day
serum creatinine
function of muscle mass and activity - why smaller for a women than a man
CrCl=
(140-age)(body wt in kg) / (SCr) (72) {cockcroft-gault formula} if a women multiply the CrCl by 85%
renal handling of a drug
renal clearance is 200 ml/min and the calculated CrCl is 94 ml/min
filtration rate > excretion rate
net reabsorption
filtration rate < excretion rate
net secretion
filtration = excretion
passes through the nephron without reabsorption or excretion
CL of the drug < inulin CL
net reabsorption
CL of the drug > inulin CL
net secretion
CL of drug = inulin CL
neither reabsorbed or secreted
renal threshold
conc of a substance in the blood above which the kidneys begin to remove it in the urine
urea renal threshold
low renal threshold - not in the blood stream
glucose renal threshold
high renal threshold
most common reason for exceeding renal threshold:
diabetes mellitus - glucose in the urine to diagnose because glucose exceeds renal threshold
Low RT: wast
high RT: stays in the blood
you can tell someone has diabetes by the glucose in the urine
threshold exceeded what happens?
excretion
long term complications of diabetes
atherosclerosis - CV problems
nervous system, eye disease, hypertension issues, vessels occluded, protein leaky in urine, kidney disease (overworking of removing excess urine and water)
Acute Renal Failure
abrupt decline due to excretion of wastes and maintaining acid/base balance
diagnosed inc serum creatnine
classification of acute renal failures
increase of SCr 0.3 mg/dl or greater or 2x increase SCr from baseline, urine output <0.5 ml/kg/hr for 6 hours
at risk groups for AKI
pre-existing renal impairment, hypertension, cardiac, diabetes, PVD, age
drug induced physiology of AKI
loss of polarity, death of cells, migration, prolipheration, differentation and reestablismment of polarity
prerenal azotemia
hemodynamics form, loss of blood volume ex: hemorrhaging
post renal obstruction
drug forms crystals and causes obstruction, severe dehydration, intervene and flush out obstruction
intrinsic AKI
damage to kidney from illness that damages cells of kidney (good pasutres), lots of inflammation
glomerular nephritis
AKI from inflammation, once treated kidney comes out of failure
regulation of K+
98% ICF, 2% ECF, normal plasma K+ is 4 mEq/L,
role of inslulin
increases uptake into the cells
role of epinephrine
increases
BP decreaes
increases renin from kidney - ACE increases
ang 2 increaes
thirst, ADH, BP, aldosterone
aldosterone stimulation for secretion
stimulation for secretion- hyperkalemia (direct action on a nephron), ang 2, hypoatremia
aldosterone inhibition for secretion
dehydration causes increase in ECF osmolarity (Na+) - decrease in total volume (water faster than Na+)
end stage renal disease
K+ 6.9(normal 3.5-5)
kalexalate
sodium polysterene sulfonate with sorbitol until K less than 5
what is given in end stage renal disease
insulin 10 units IV, Dextrose IV (maintain glucose, produces insulin which causes cellular uptake of K+ because insulin release), Albuterol inhalation (B2 receptor releases epi, produces insulin)
ADH
antidiuretic hormone/vasopressin/AVP
released from the posterior pituitary when dehydration occurs, kidney water reabsorption
ADH secreted in response to
decrease in volume, atria stretch goes down (volume decrease, CO decrease, pumping less) - increase plasma osmolarity
water channels in collecting duct ADH
vasopressin binds to the membrane receptor, receptor activates cAMP, cell inserts AQP2 water pores into the apical membrane, water is absorbed by osmosis into the blood
diseases associated with ADH
diabetes insipidus ( dilute urine output, hyperatremia, polyuria, polydipsia, high plasma osmolarity, normoalkemia)
central - lack of production
nephrogenic- lack of response
syndrome of inappropriate (too much) ADH (SIADH)
ADH release with normal stimuli, common in hospitalized elderly patients, caused by tumors, pulmonary disorders, TB, hyperthyroidism, drugs - dilutional hypoatremia, neurological signs
sweat Na+ conc
30-50
sweat K+ conc
5
sweat H+ conc
-
sweat Cl- conc
45-55
sweat HCO3- conc
-
gastric Na+ conc
40-65
gastric K+ conc
10
gastric H+ conc
90
gastric cl- conc
100-140
gastric HCO3- conc
-
diarrhea Na+ conc
25-50
diarrhea K+ conc
35-60
diarrhea H+ conc
-
Diarrhea Cl- conc
20-40
Diarrhea HCO3- conc
30-45
hypernatremia volume depletion
thirsting, sweating
hypernatremia volume expansion
hypertonic infusion
hypoatremia volume depletion
diarrhea, burns, vomiting, diuretics
hypoatremia volume expansion
congestive heart failure
natriuretic peptide
decrease systemic vascular resistance
natriuretic peptide
induces sodium release from the kidneys
decreases systemic vascular resistance
decreases blood volume
increase CO
atrial natriuretic peptide
released from the atria from stretching when more volume is coming in Na+/H2O excretion decreases renin afferent dilate efferent constrict ENaC inhibits PGC increases aldosterone decreases Antagonist RAAS Blood volume decreases increases lipolysis
B-Natriuretic Peptide
secreted in ventricles, increases diuresis Na+ and H2O, volume decreased overall, decrease in BP,
Nesiritide
BNP, treats decompensated heart failure
BNP and clinical outcomes
increase in patients with worse outcomes
increase in renal failure
decrease in obesity
why is there a resulting excretion of NaCl and H2O in natriuretic peptides
less vasopressin, increased GFR, decreased renin (less aldosterone), decreased blood pressure
normal ranges of pH, Na, K
Na: 135-140
K: 3.5-5
pH: 7.38 - 7.42
H+: 38-42 nanomolar
life can’t exist outside of what pH = why?
pH 6.8 - 7.8
K+ disturbances causes arrhythmias, contraction, acidosis, alkalosis, acidosis causes CNS suppression (respiratory issue)
metabolism of carbs and fats generates
CO2
metabolism of cys and met generates
sulfuric acid
metabolism of lys, arg, his generates
HCl
metabolism of Glu, Asp, citric acid generates
bicarbonate
dietary intake of phosphate
coke, cheese, hot dogs
3 sources of acids and bases in the body
- buffering 2. renal 3. respiratory
phosphate site of action
plasma and urine
protein site of action
intracellular
organic phosophate site of action
intracellular
bicarb site of action
extracellular
what determiens how much acid can be buffered
how much before you can add before you see a change in pH
CO2 reacts with water to produce what
carbonic acid
pH =
6.1 + log ( [HCO3-] / 0.03 x Pco2)
why is this such a good buffering system?
system is an open system: constantly changing and can add in the respiratory components. weak acid can be adjusted to meet the bodies needs. removal of CO2 by respiration or addition of CO2 by metabolism keeps the HCO3 : CO2 ratio near 20
clinical correlation: increasing ketoacids
added H+, respiration will increase, renal will increase, bicarb dec, PCO2 increase
metabolic acidosis
HCO3 < 24
- respiratory compensation: PCO2 < 40 mmHg
- Cause: addition of acid/loss of base
respiratory acidosis
PCO2 > 40 mmHg
- renal compensation, HCO3 > 24 mmHg
cause: decreased ventilation
metabolic alkalosis
HCO3 > 24
- respiratory compensation, PCO3 > 40 mmHg
cause: addition of base, loss of acid
respiratory alkalosis
PCO3 < 40 mmHg
- renal compensation, HCO3 < 24
cause: increased ventilation
renal correction in metabolic acidosis
increased acid titration : Increased NH3, increased HPO4-
increased acid excretion in the urine, increased bicarb regeneration. INC PH
respiratory compensation metabolic acidosis
hyperventilation, dec pco2, dec H2CO3, dec H+, dec CO2 + H2O
reabsorption of bicarbonate
bicarbonate enters the tubular fluid by glomerular filtration
forms H2CO3, converts to H2O and CO2 by carbonic anhydrase
CO2 can freely diffuse into proximal tubule cells, reacts with H2O inside to form HCO3- and H+, gets transported into PT capillaries across the basolateral membrane
formation of ammonium
produced from glutamine in tubular cells
ammonium ion in the filtrate gets excreted removing H+
acidosis and K+
collecting duct cells secrete H+ into the filtrate, this is done in exchange for K+ reabsorption, K+ increases in acidosis, secreted protons buffered by phosphate in the tubular fluid
alkalosis and K+
cells in the collecting duct secrete bicarb and reabsorb H+, K+ exchanged for H+ to maintain neutrality, hypokalemia
renal H+ excretion and HCO3- reabsorption / generation
normal: kidneys eliminate H+ and reabsorb new HCO3-
alkalosis: kidneys reduce secretion of H+ and secrete HCO3-
acidosis: kidneys increase secretion of H+ and increase formation/reabsorption of HCO3-
diabetic ketoacidosis
increases ketoacids, K+ increase, pH < 7.4 (not complying with insulin therapy)
profuse vomiting
loss of HCl, K+ decrease, pH > 7.4, metabolic
ingestion of antacid
addition of base, pH > 7.4, K+ decreased
profuse diarrhea
loss of HCO3-, K+ increased, pH decreased, metabolic
hypervenhilation
alkylosis
hypovenhilation
acidosis
AKI stage 1 defined by
increase SCr 0.3 or increase from baseline 1.5-2x WITH urine output < 0.5 for 6 hrs
pre renal injury symptoms
high BUN, increased SCr, edema in lower extremities
intrinisic kidney injury symptoms
crush injury (inc creatinine kinase), high SCr, may have fever (inflammation)
postrenal kidney injury symptoms
increased SCr, inc WBC, urine pH on low end
prerenal cause
azotemia, hemodynamic form due to hypoperfusion, dec volume, hemorrhage, heart failure, narrowing of artery
intrinsic cause
damage to the kidney itself from vasculitis or inflammation
postrenal
due to volume contraction or drugs resulting from formation of obstruction
treatment for kidney injury
hemodialysis, IV fluid, blood, blood products, dopamine dobutamine to inc CO - inc GFR
normal range SCr
1 - 1.5
normal range BUN
7 - 20
normal range CrCl
125
HCO3- higher in ICF or ECF
ECF
pH more acidic (lower) in ICF or ECF
ICF
Na / K more concentrated in ICF or ECF
K more in ICF
Na more in ECF
drugs, pain, fear, anxiety, aspirin causes respiratory acidosis or alkalosis?
alkalosis
some dugs, emphysemia, pulmonary edema cause acidosis or alkalosis?
acidosis
