Renal Physiology Part 3 Flashcards
Countercurrent multiplier mechanism
- concentrates solute in medullary interstitium via 2 primary mechanisms:
- Na-K-2Cl cotransporter reabsorption of Na in the TAL
- reabsorption of urea initiated by ADH
- high solute concentration enables kidneys to excrete highly concentrated urine, conserve water during periods of dehydration
- this mechanism requires integrated function of descending, ascending limbs; vasa recta capillaries; collecting ducts
Any drugs which increase renal blood flow to vasa recta or inhibit the loop transporter will
decrease the renal medullary interstitial osmolarity and reduce the kidney’s ability to produce a concentrated urine
ADH
- increase H2O and urea permeability of late distal tubule, collecting duct
- stimulates water reabsorption in principal cells via V2 receptor
- also vasoconstrictor arterioles (V1 receptor) and thus can serve as a hormonal regulator of vascular tone
2 primary regulators of ADH are
- plasma osmolality: an increase stimulates, while a decrease inhibits
- blood pressure/volume: an increase inhibits, while a decrease stimulates
In well-hydrated individuals (diuresis) collecting duct
is normally impermeable to water
- water remains in tubular lumen; dilute urine is excreted
- low ADH
In dehydrated individuals (antidiuresis) collecting duct
is highly water-permeable
- water is reabsorbed; low volume of concentrated urine is excreted
- high ADH
ADH promotes urea
reabsorption from inner medullary collecting duct by increasing expression of urea transporters
Antidiuresis: high ADH
- ADH makes the collecting duct epithelial highly water permeable
- water is reabsorbed in this segment, and a low volume, highly concentrated urine is excreted
- SIADH, dehydration
Water diuresis: low ADH
- high volume of dilute urine is excreted
- collecting duct epithelium is impermeable to water
- lower solute concentrations in medullary interstitium
- diabetes insipidus, volume expansion
ANP
- increases GFR: afferent arteriolar dilation, efferent arteriolar constriction
- inhibits Na+ reabsorption in medullary CD
- suppresses renin secretion
- suppresses aldosterone secretion
- a systemic vasodilator
- suppresses AVP secretion, actions
Free water clearance (Ch2o)
excretion of solute-free water by the kidneys
-Ch2o=V-Cosm
If Uosm
positive; pure water is cleared from the body
If Uosm > Posm, Ch2o
is negative; pure water is retained
Fractional Excretion
(Una x Pcreat)/(Pna x Ucr) x 100
Fractional excretion below 1%
- prerenal and AGN
- Na avidly reabsorbed
Fractional excretion greater than 2%
- ATN, renal
- tubular damage disrupts normal Na reabsorption
3 lines of defense against pH changes
- chemical buffers
- respiration
- kidneys
6 factors control renal H+ secretion
-intracellular pH, plasma Pco2, carbonic anhydrase, Na+ reabsorption, extracellular K+, aldosterone
Respiratory acid-base disturbances:
-primary changes in Pco2 cause H+ and HCO3- to change
Metabolic acid-base disturbances
-gains or losses of H+ and HCO3-; respiratory, renal responses
H+ competes with
Ca2+ for binding sites on plasma proteins
Acidemia
increased [H+] = increase plasma free [Ca2+]
- hypercalcemia
- decreased pH–H+ displaces Ca2+ from proteins
Alkalemia
decreased [H+] = decreased plasma free [Ca2+]
-hypocalcemia
Acidosis
- increased H+
- hyperkalemia
- K+ shifting out of cell into ECF
- Na+ shifting out of cell into ECF
- H+ moving into cell
Alkalosis
- hypokalemia
- decreased H+
- H+ moving out of cell
- K+ moving into cell
- Na+ moving into cell
Respiratory alkalosis
- decreased CO2+; equation shifted towards CO2
- compensate by decreasing HCO3-; pH increases
- PCO2
Respiratory acidosis
- increased CO2+; equation shifted towards HCO3-
- compensate by increasing HCO3-; pH decreases
- PCO2>40
- renal compensation
Metabolic alkalosis
- increased HCO3-; equation shifted towards CO2
- compensate by increasing CO2; pH increases
- HCO3- > 24
- respiratory compensation
Metabolic acidosis
- decreased HCO3-; equation shifted towards HCO3-
- compensate by decreasing CO2; pH decreases
- PCO2
Anion gap
- differential diagnosis of metabolic acidosis
- cations - anions (sodium - (chloride + bicarbonate)
- Normal range: 8-11
- anion gap is either normal or increased, depending on cause of metabolic acidosis
Anion Gap Hyperchloremic acidosis
- AG is unchanged
- loss of HCO3- is matched by gain of Cl-
High Anion Gap acidosis
-HCO3- is replaced by unmeasured anion (lactate, ketoacidosis, poisoning)
Causes of high anion gap acidosis
- Ethanol
- Ethylene glycol
- Lactic acid
- Methanol
- Paraldehyde
- Aspirin
- Renal Failure
- Ketone bodies
Renin
-catalyzes conversion of angiotensinogen to angiotensin I, which in turn is converted to Ang II by ACE
3 primary regulators of renin are
- perfusion pressure to the kidney: an increase inhibits, while a decrease stimulates
- sympathetic stimulation to the kidney (direct effect via B-1 receptors)
- Na+ delivery to the macula densa: an increase inhibits, while a decrease stimulates
A patient with essential hypertension has
- increased renal artery pressure leading to vasoconstriction of the afferent arterioles and vasodilation of the efferent arterioles
- high pressure in the juxtaglomerular apparatus leads to decreased renin secretion–>low angiotensin II–>vasodilation of the efferent arterioles
A patient with renal artery stenosis has
low renal artery pressures, leading to low pressures at the afferent arterioles
-vasodilation of the afferent arterioles and vasoconstriction of the efferent arterioles (increased renin secretion leads to increased angiotensin II)
For a patient who has diarrhea, vomiting, or hemorrhaging, it is important to
preserve extracellular volume
-one way to do so is to increase reabsorption of fluid an electrolytes at the proximal tubules
In nephrogenic diabetes insipidus,
- ADH receptors are not functioning and it is not possible to increase reabsorption at the CD.
- the patient loses free water and develops hypernatremia
- treatment is reduction of ECF volume with a thiazide diuretic.
- this increases peritubular oncotic pressure, in turn increasing water reabsorption in the proximal tubule.
- elevated water reabsorption, along with sodium loss in the urine, corrects hypernatremia
Stimulation of the sympathetic neurons to the kidney causes
- vasoconstriction of the arterioles, but has a greater effect on the afferent arteriole
- as a consequence: RPF, PGC, GFR decreases; FF increases; PPC decreases; oncotic pC increases
- increased forces promoting reabsorption in the peritubular capillaries because of a lower peritobular capillary hydrostatic pressure and an increase in plasma oncotic pressure (FF increases)
Angiotensin II
- vasoconstrictor
- constricts both afferent and efferent arterioles, but it has a bigger effect on efferent arteriole
- RPF decreases; PGC, GFR, FF increase; PPC decreases; oncotic PC increases
- increasing forces promoting reabsorption in the peritubular capillaries because of a lower peritubular capillary hydrostatic pressure and an increase in plasma oncotic pressure (FF increases)
During a stress response, there is
- increase in both sympathetic input and very high levels of circulating ang II
- increased SNS tone to the kidneys and very high levels of ang II vasoconstrictor both afferent and efferent arterioles. There is a large drop in the RPF and only a small drop in GFR
- increase in FF–>increase in oncotic pressure–>increase in reabsorption in proximal tubules
- less fluid is filtered and a greater percentage of that fluid is reabsorbed in the PT, leading to preservation of volume in a volume depleted state
- also an increase in ADH due to low volume state
- activation of SNS also directly increases renin release
Net effect of ang II is to
preserve GFR in volume-depleted state
-prevents a large decrease in GFR but allows a beneficial small decrease
In nephrotic syndrome, there is
- marked disruption of the filtering membrane, so plasma proteins now pass through the membrane and are eliminated in urine
- typically associated with a non-inflammatory injury to the glomerular membrane system
- marked proteinura; edema; hypoalbuminemia; lipidura; hyperlipdemia
In nephritic syndrome, there is
an inflammatory disruption of the glomerular membrane system.
- this disruption allows proteins and cells to cross filtering membrane
- proteinuria
Filtered load=
GFR x Px
Filtered load > excretion
-net reabsorption
Filtred load
net secretion
Clearance of inulin
- independent of plasma concentration
- inulin neither secreted nor reabsorbed
At low plasma levels, clearance of glucose is
zero, because all is reabsorbed
Glucose appears in urine when
filtered load exceeds TM
Primary site of action for carbonic anhydrase inhibitors is the
PT
-blocking CA reduces bicarbonate reabsorption and the activity of the Na+–H+ exchanger
Loop diuretics block
the Na+-K+-2Cl- transporter in the ATL, thereby reducing their reabsorption
-blocking this transporter also reduces calcium and magnesium reabsorption, all of which results in a marked diuresis
Bartter’s syndrome
- a genetic mutation resulting in diminished function of the Na/K/2Cl transporter
- leads to a low volume state, which causes an increase in renin and aldosterone
- patients exhibit hypokalemia, alkalosis, and elevated urine calcium
Familial hypocalciuric hypercalcemia
-autosomal dominant genetic disorder resulting in hypercalcemia
-CaSR is mutated such that it does not respond to plasma calcium.
calcium reabsorption in the kidney is elevated despite hypercalcemia
-patients also have high levels of PTH because CaSR is expressed in cells of the parathyroid gland
Potassium sparing diuretics work by
blocking ENaC or by blocking aldosterone receptors or the production of aldosterone
-sodium reabsorption is reduced and potassium secretion is diminished
Liddle’s syndrome
- a genetic disorder resulting in a gain of function of ENaC channels in the CD
- results in enhanced sodium reabsorption and potassium secretion.
- patients are hypertensive, hypokalemic, and alkalotic
A decrease in free calcium is a signal to
- increase PTH secretion and the function of PTH is to raise free calcium
- PTH increases Ca2+ reabsorption in PT of the kidney; inhibits phosphate reabsorption in PT; stimulates 1-alpha-hydroxylase enzyme in kidney, converting inactive vitamin D to active form; causes bone resorption, releasing Ca2+ and Pi into the blood
