Lecture 3 Renal Flashcards
normal pH range of body fluids and concentration of HCO3
7.35-7.45
HCO3= 24 mM
if pH 7.8 life can not be sustained
the greatest concern of the body is too much acid or base?
TOO MUCH ACID. body produces more acid than base
what are volatile acids
volatile acids are by products of metabolism that can be exhaled or dissipated by lungs Ex: CO2 bc it produces H in water of body fluids
What are nonvolatile acids
non volatile acids arise from metabolism or the diet Ex: phosphoric, lactic, and sulfuric acid and KETONES
how does body handle non volatile acid
neutralizes them with HCO3, regulated by renal system
theory says amount of acid in urine should equal the NonVolatile load how is this accomplish
the kidney does this by reabsorbing all filtered bicarbonate and then producing enough bicarbonate to neutralize acids produced by body
what is the lowest pH of urine possible? and what does this tell us
lowest urine pH can be is 4.4 so body has to excrete more acid than can be held in a solution of pH = 4.4
how does kidney excrete more acid than a pH of 4.4 will allow?
BUFFERING!
buffers bind to excess or free H to INC acid carried in urine without decreasing the pH
what molecules serve as buffers
HCO3, phosphate and ammonium
phosphate as a buffer
phosphate is used first but small supply
ammonium as a buffer
ammonium produced within tubular cells eliminates H and produces HCO3 that is reabsorbed
Net acid excretion should remove all non volatile acids what forms are secreted
free H
HPO4(-2)
and NH4
what two acids are titratable and what 1 acid is NOT Titratable
H and HPO4 (-2) ARE TITRATABLE
NH4 is NOT titratable
URINE has all 3!
under normal conditions what does the kidney do t regulate the acidity of urine
regulates HCO3 reabsorption by excreting acid equal to the non volatile load and replenishing the HCO3 lost to the neutralization of the acids
what are the 3 options for renal regulation of body pH that will produce an alkaline urine and acidifies body fluids
- DEC body pH by not reabsorbing HCO3 this urine is alkaline and body fluids acidic
- no effect on body pH by reabsorbing all HCO3, urine is neutral
- INC body pH by reabsorbing all and producing more HCO3, produces and acidic urine and basic body fluids
what happens due to the fact that HCO is NOT directly transported from tubular fluid into blood
HCO3 production and reabsorption results in H secretion`
what produces H and HCO in the tubular epithelium
Carbonic Anhydrase activity
How is H secreted after production by CA
H is secreted via Na H antiporter and via H ATPase pump and H/K ATPase pump which secretes H
how is HCO3 reabsorbed
HCO3 is reabsorbed/ transported across basolaterial membrane
Where does CA activity take place to produce H and HCO3
CA = late distal tubule and Collecting duct
what do intercalated cells doe in the late distal tubule and collecting ducts
reverses H and HCO3 transporters to the basolateral and apical membranes, THUS causing reabsorption of H and secretion of HCO3
VEYR LOW activity usually
if body is alkaline what must kidney do
produce alkaline urine by INC excretion of HCO3 and not neutralizing all the HCO3 in the tubular fluid
What do cells in the proximal tubule do regarding pH
PCT detects intracellular pH and can alter CA activity
when does kidney use phosphatase as an additional buffer
when body is acidic so it can INC excretion of H
after all HCO has been reabsorbed and HPO4 is depleted what will kidney do
Kidney produces the 3RD buffer of ammonium to INC H secretion
Ammonium must be kept from what
NH4 must NOT enter body where it would become urea and produce H
where is NH4 produced and by metabolism of what
NH4 produced in PCT by metabolism of glutamine
what up regulates synthesis of glutamine metabolism enzymes
acidosis- but longggg time
how is NH4 added to urine
by diffusion trapping
explain diffusion trapping of NH4
NH4 substitutes for K and the NaKCl2 symporter and enters the interstitial fluid- once in the interstitial fluid the polar molecule of NH4 is trapped but NH3 can diffuse into the collecting ducts thus once in the tubule NH3 is protonated by excess H producing NH4 and eliminated with the urine
key points of regulation of acid base balance by kidneys
respiratory system keeps Pco2 constant and kidneys regulate bicarbonate
urine typically acidic
net acid excretion occurs after all filtered bicarbonate is reabsorbed
additional H must be buffered
new bicarbonate made in PCT by NH4 from glutamine
NH4 produced in PCT facilitates H excretion in collecting duct as a result of diffusion trapping
4 ways body gains H ions
generation of H from CO2
production of non volatile acids
gain of H from loss of bicarbonate in diarrhea and GI fluids
due to loss of bicarbonate in urine
4 ways body loses H ions
utilization of H ion in metabolism of organic ions
in vomitus
in urine
from hyperventilation
4 disorders of acid base changes
respiratory acidosis
respiratory alkalosis
metabolism acidosis
metabolism alkalosis
what is respiratory acidosis
low pH due to CO2 build up
what does respiratory acidosis causes
impaired pulmonary function
and a renal compensatory response leading to production of HCO3
respiratory acidosis cause example
hypoventilation i.e. holding breath
respiratory alkalosis?
high pH due to low PCO2
cause of respiratory alkalosis
HYPERventilation, anxiety, altitude, fever, drugs
kidney response to respiratory alkalosis
excrete HCO3 to lower pH
what is metabolic acidosis
low pH due to low HCO3
what are the compensatory responses to metabolic acidosis
HYPERventilation
Renal= produce new HCO3
causes of metabolic acidosis
diabetic ketosis, diarrhea, renal failur
what is metabolic alkalosis
high pH due to INC HCO
causes of metabolic alkalosis
Vomitting, antacids, hemorrhage
compensatory responses due to metabolic alkalosis
HYPOventilate
renal= excrete HCO3
where is Ca found
interstitial fluid, extracellular fluid and bone
why is it important to regulate Ca
hypocalcemia INC Excitability of neural and muscle tissue- tetany
HYPERcalcemia causes cardiac arrhythmias and disorientation can cause death
A dec in plasma pH will ____ to the amount of free Ca which can be filtered and excreted so ____ can lead to _____
DEC plasma pH INC free Ca
INC free Ca leads to secretion of Ca causing alkalosis and leading to HYPOcalcemia
what 3 hormones regulate Ca
PTH
Calcitriol (1,25 dihyrdroxyvitain D) and Calcitonin
what regulates the 3 Ca regulating hormones and where is it found?
Ca sensing receptor (CaSR) found in plasma membrane of cells in parathyroid, thryroid and proximal tubule
PTH
release why?
Does what?
PTH released in response to hypocalcemia
INC bone resorption and INC renal Ca reabsorption and stimulates calcitriol production
Calcitriol (1, 24 dihydroxyvitamin D)
released why?
does what?
Calcitriol is made by metabolism of Vit D stimulated by hypocalcemia and hypophosphatemia and stimulated by PTH
action: INC transport mechan for Ca reabsorption in SI and facilitates action of PTH and INC renal Ca transport
Calcitonin
released why?
does what?
Calcitonin released in response to HYPERcalcemia
INC bone deposition
What drugs respond to HYPOcalcemia
PTH and Calcitriol
what drugs respond to HYPERcalcemia
CALCITONIN!
describe Ca reabsorption in nephron
PCT = paracellular transport and solvent drag
THICk ascending limb- para and transcellular transport
DCT- transcellular reabsorption of Ca regulated by expression of Ca transported regulated by PTH
Collecting duct - not significant for Ca
