Term
Causes of shift of K+ out of cells =>
Hyperkalemia |
|
Definition
Insulin deficiency
Beta-blockers
Acidosis (exchange of EC H+ for IC K+)
Hyperosmolarity (H2O flows out of the cell; K+ diffuses out with H2O)
Inhibitors of Na+-K+ pump (when pump is blocked, K+ is not taken up into cells)
Exercise
Cell lysis |
|
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Term
Cuases of Shift of K+ into cells =>
Hypokalemia |
|
Definition
Insulin
Beta-adrenergic agonists
Alkalosis (exchange of IC H+ for EC K+)
Hyposmolarity (H2O flows into cell; K_ diffuses in with H2O) |
|
|
Term
Na+ reabsorption in the proximal tubule
- general features
- early PT
- late PT
- what are the effects of ECF volume contraction and expansion on reabsorption in the PT |
|
Definition
Reabsorbs 67% of filtered Na+ and H2O
GT balance (maintains constant fractional reabsorption; i/c GFR & filtration fraction --> i/c protein conc & oncotic pressure --> i/c fluid reabsorption)
Process is isosmotic (TF/P = 0)
Early PT:
- cotransport of Na+ with glucose, amino acids, Pi, lactate
- Na+-H+ countertransport
- carbonic anhydrase inhibitors inhibit the reabsorption of filtered HCO3-
Late PT:
- Na+-Cl- cotransport
ECF volume contraction --> i/c peritubular capillary oncotic pressure, d/c hydrostatic pressure --> *i/c PT reabsorption*
ECF volume expansion --> d/c peritubular capillary oncotic pressure, i/c hydrostatic pressure --> *d/c PT reabsorption* |
|
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Term
| Na+ reabsorption in the thick ascending limb of Henle's loop |
|
Definition
reabsorbs 25% of filtered Na+
Na+-K+-2Cl- cotransporter
loop diuretics inhibit Na+-K+-Cl- cotransporter
impermeable to water - diluting segment
lumen-positive potential difference (some K+ diffuses back into lumen) |
|
|
Term
Na+ reabsorption in distal tubule & collecting duct
- early DT
- late DT (2 cell types) |
|
Definition
reabsorb 8% of filtered Na+
early DT:
- Na+-Cl- cotransporter
- site of action of thiazide diuretics
- impermeable to water (cortical diluting segment)
late DT:
- principal cells
reabsorb Na+ and H2O
secrete K+
aldosterone increases Na+ reabsorption and increases K+ secretion
ADH increases H2O permeability
K+-sparing diuretics d/c K+ secretion
- alpha-intercalated cells
secrete H+ via H+-ATPase (stimulated by aldosterone)
reabsorb K+ via H+,K+-ATPase |
|
|
Term
Causes of increased distal K+ secretion
(--> hypokalemia) |
|
Definition
ThHigh-K+ diet
hyperaldosteronism
alkalosis
thiazide diuretics
loop diuretics
luminal anions |
|
|
Term
Causes of decreased distal K+ secretion
(--> hyperkalemia) |
|
Definition
low-K+ diet
hypoaldosteronism
acidosis
K+-sparing diuretics |
|
|
Term
K+ reabsorption in the nephron
- PCT
- TAL
- DCT & collecting duct |
|
Definition
PT reabsorbs 67% of filtered K+
TAL reabsorbs 20% of filtered K+ via Na+-K+-Cl- cotransporter
DT & CD reabsorb or secrete K+, depending on K+ intake
- reabsorption involves H+,K+-ATPase in alpha-intercalated cells; only on a low-K+ diet
- secretion occurs in principal cells; variable, acc to dietary K+, aldosterone, acid-base status, urine flow rate |
|
|
Term
|
Definition
50% of filtered urea is reabsorbed in the PT
ADH increases the urea permeability of the inner medullary collecting ducts; this contributes to urea recycling in the inner medulla
high levels of water reabsorption/low urine flow => d/c urea excretion
low levels of water reabsorption/high urine flow => i/c urea excretion |
|
|
Term
| Renal regulation of PHOSPHATE |
|
Definition
85% of filtered Pi is reabsorbed in PT by Na+-Pi cotransport across luminal membrane and Pi-anion exchange in BL membrane (15% is excreted in urine)
PTH inhibits Pi reabsorption (activates adenylate cyclase, makes cAMP, inhibiting Na+-Pi cotransport)
Pi reabsorption is saturable (PTH lowers Tm, thereby i/c Pi excretion)
Pi is a urinary buffer (excretion of H2PO4- is called titratable acid) |
|
|
Term
Renal regulation of Ca++
- proximal tubule
- TAL
- distal tubule and collecting duct |
|
Definition
60% of plasma Ca++ is filtered; the PT and TAL reabsorb >90% (passive)
- Ca++ ATPase and Ca++/Na+ exchange in basolateral membrane reabsorb Ca++
- paracellular reabsorption also occurs (but not in DT)
TAL: paracellular reabsorption of Ca++ via tight junctions is driven by the +6mV in the lumen
- this is also the main way Mg++ is reabsorbed!
Loop diuretics cause i/c urinary Ca++ excretion - can treat hypercalcemia
DT & CD reabsorb 8% (active):
PTH & thiazide diuretics i/c Ca++ reabsorption
Calcitonin and calcitriol (vit D) further activate Ca++ reabsorption |
|
|
Term
Renal regulation of Mg++
(where is it reabsorbed?) |
|
Definition
bulk is reabsorbed in PT by paracellular mvmt
- the 6 mV transepithelial potential (lumen positive) is the driving force for Mg++ reabsorption
By inhibiting the Na,K,2Cl cotransporter, loop diuretics lower the trans-epithelial potential, the driving force for Mg reabsorption
- So loop diuretics can cause hypomagnesemia
In TAL, Mg++ and Ca++ compete for reabsorption |
|
|
Term
| Responses to water deprivation |
|
Definition
Water deprivation -->
I/c plasma osmolarity -->
stimulates osmoreceptors in anterior hypothalamus -->
i/c secretion of ADH from posterior pituitary -->
i/c water permeability of late DT & CD -->
i/c water reabsorption -->
i/c urine osmolarity, d/c urine volume -->
d/c plasma osmolarity toward normal |
|
|
Term
| Responses to water intake |
|
Definition
water intake -->
d/c plasma osmolarity -->
inhibits osmoreceptors in anterior hypothalamus -->
d/c secretion of ADH from posterior pituitary -->
d/c water permeability of late DT & CD -->
d/c water reabsorption -->
d/c urine osmolarity, i/c urine volume -->
i/c plasma osmolarity toward normal |
|
|
Term
Free-water clearance
absence of ADH: CH2O is _______
presence of ADH: CH2O is ________ |
|
Definition
used to estimate the ability to concentrate or dilute the urine
CH2O = V - Cosm
absence of ADH: CH2O is positive
presence of ADH: CH2O is negative |
|
|
Term
| Countercurrent multiplication in the loop of Henle |
|
Definition
establishes the corticopapillary osmotic gradient (300 mOsm/L in cortex, to 1200 mOsm/L in papilla)
depends on NaCl reabsorption in the TAL and countercurrent flow in the descending and ascending limbs
augmented by ADH - ADH i/c the size of the corticopapillary osmotic gradient
the vasa recta maintain the countercurrent exchange |
|
|
Term
Various elements of the nephron under *high vs. no ADH*
corticopapillary osmotic gradient
proximal tubule
thick ascending limb of Henle's loop
early distal tubule
late distal tubule & collecting ducts |
|
Definition
Corticopapillary osmotic gradient:
smaller when there is no ADH, b/c ADH stimulates both countercurrent multiplication and urea recycling
PT: always isosmotic, TF/Posm = 1.0, not under hormonal control
TAL: impermeable to H2O, TF/Posm < 1.0 always
early DT: reabsorbs NaCl but is impermeable to water, always TF/Posm < 1.0
late DT & CD:
high ADH: TF/Posm = 1.0 at end of DT, TF/Posm > 1.0 at end of CD b/c ADH i/c the H2O permeability of the principal cells
low ADH: cells are impermeable to H2O, TF/Posm < 1.0 |
|
|
Term
In PRIMARY POLYDIPSIA, what are the following values, relative to normal:
Serum ADH
Serum Osmolarity/Serum [Na+]
Urine osmolarity
Urine flow rate
CH2O |
|
Definition
Serum ADH: D/C
Serum Osmolarity/Serum [Na+]: D/C
Urine osmolarity: HYPOSMOTIC
Urine flow rate: HIGH
CH2O: POSITIVE |
|
|
Term
In CENTRAL DIABETES INSIPIDUS, what are the following values, relative to normal:
Serum ADH
Serum Osmolarity/Serum [Na+]
Urine osmolarity
Urine flow rate
CH2O |
|
Definition
Serum ADH: D/C
Serum Osmolarity/Serum [Na+]: I/C
Urine osmolarity: HYPOSMOTIC
Urine flow rate: HIGH
CH2O: POSITIVE |
|
|
Term
In NEPHROGENIC DIABETES INSIPIDUS, what are the following values, relative to normal:
Serum ADH
Serum Osmolarity/Serum [Na+]
Urine osmolarity
Urine flow rate
CH2O |
|
Definition
Serum ADH: I/C
Serum Osmolarity/Serum [Na+]: I/C
Urine osmolarity: HYPOSMOTIC
Urine flow rate: HIGH
CH2O: POSITIVE |
|
|
Term
In WATER DEPRIVATION, what are the following values, relative to normal:
Serum ADH
Serum Osmolarity/Serum [Na+]
Urine osmolarity
Urine flow rate
CH2O |
|
Definition
Serum ADH: I/C
Serum Osmolarity/Serum [Na+]: HIGH-NORMAL
Urine osmolarity: HYPEROSMOTIC
Urine flow rate: LOW
CH2O: NEGATIVE |
|
|
Term
In SIADH, what are the following values, relative to normal:
Serum ADH
Serum Osmolarity/Serum [Na+]
Urine osmolarity
Urine flow rate
CH2O |
|
Definition
Serum ADH: VERY I/C
Serum Osmolarity/Serum [Na+]: D/C
Urine osmolarity: HYPEROSMOTIC
Urine flow rate: LOW
CH2O: NEGATIVE |
|
|
Term
*PTH*
Stimulus for secretion
Time course
Mechanism of action
Actions on kidneys |
|
Definition
Stimulus: d/c plasma [Ca++]
Time course: fast
Mechanism of action: basolateral receptor, adenylate cyclase, cAMP -> urine
Actions: d/c Pi reabsorption (PT), i/c Ca++ reabsorption (DT) |
|
|
Term
*ADH*
Stimulus for secretion
Time course
Mechanism of action
Actions on kidneys |
|
Definition
Stimulus: i/c plasma osmolarity, d/c blood volume
Time course: fast
Mechanism of action: basolateral V2 receptor, adenylate cyclase, cAMP
Actions: i/c H2O permeability (late DT & CD principal cells) |
|
|
Term
*ALDOSTERONE*
Stimulus for secretion
Time course
Mechanism of action
Actions on kidneys |
|
Definition
Stimulus: i/c circulating AT-II, i/c plasma [K+]
Time course: slow
Mechanism of action: new protein synthesis
Actions: i/c Na+ reabsorption (DT principal cells), i/c K+ secretion (DT principal cells), i/c H+ secretion (DT alpha-intercalated cells) |
|
|
Term
*ANP* (BNP has similar effects)
Stimulus for secretion
Time course
Mechanism of action
Actions on kidneys |
|
Definition
Stimulus: i/c atrial pressure
Time course: fast
Mechanism of action: guanylate cyclase, cGMP
Actions: i/c GFR (AA dilation, EA constriction), inhibits Na+ reabsorption (medullary CD), suppressed renin/aldosterone/ADH secretion, systemic vasodilation => i/c Na+ excretion |
|
|
Term
*ANGIOTENSIN II*
Stimulus for secretion
Time course
Mechanism of action
Actions on kidneys |
|
Definition
Stimulus: d/c blood volume (via renin)
Time course: fast
Mechanism of action: ?
Actions: i/c Na+-H+ exchange and HCO3- reabsorption (PT) |
|
|
Term
In METABOLIC ACIDOSIS:
which elements of CO2 + H2O <-> H+ + HCO3- are affected?
Respiratory/renal compensation? |
|
Definition
CO2 is decreased (respiratory compensation)
HCO3- is decreased (cause)
H+ is increased
Hyperventilation |
|
|
Term
In METABOLIC ALKALOSIS:
which elements of CO2 + H2O <-> H+ + HCO3- are affected?
Respiratory/renal compensation? |
|
Definition
CO2 is increased (respiratory compensation)
HCO3- is increased (cause)
H+ is decreased
Hypoventilation |
|
|
Term
In RESPIRATORY ACIDOSIS:
which elements of CO2 + H2O <-> H+ + HCO3- are affected?
Respiratory/renal compensation? |
|
Definition
CO2 is increased (cause)
H+ and HCO3- are both increased
Renal compensation: i/c H+ excretion, i/c HCO3- reabsorption |
|
|
Term
In RESPIRATORY ALKALOSIS:
which elements of CO2 + H2O <-> H+ + HCO3- are affected?
Respiratory/renal compensation? |
|
Definition
CO2 is decreased (cause)
H+ and HCO3- are both decreased
Renal compensation: d/c H+ excretion, d/c HCO3- reabsorption |
|
|
Term
CARBONIC ANHYDRASE INHIBITORS
drug names
site of action
mechanism
major effects |
|
Definition
ACETAZOLAMIDE
proximal tubule
inhibition of carbonic anhydrase -> inhibits HCO3- reabsorption
i/c HCO3- excretion; retains H2O in lumen, acidifies the blood |
|
|
Term
LOOP DIURETICS
drug names
site of action
mechanism
major effects |
|
Definition
FUROSEMIDE, TORSEMIDE
TAL
Inhibit Na+-K+-Cl- cotransport
i/c NaCl excretion
i/c K+ excretion (i/c DT flow rate)
i/c CA++ excretion
d/c ability to concentrate urine (d/c corticopapillary gradient)
d/c ability to dilute urine (inhibition of diluting segment) |
|
|
Term
THIAZIDE DIURETICS
drug names
site of action
mechanism
major effects |
|
Definition
CHLOROTHIAZIDE, HYDROCHLOROTHIAZIDE, CHLORTHALIDONE, (INDAPAMIDE, METOZALONE)
early DT (cortical diluting segment)
inhibition of Na+-Cl- cotransport
i/c NaCl excretion
i/c K+ excretion (i/c DT flow rate)
d/c Ca++ excretion
d/c ability to dilute urine (inhibition of cortical diluting segment)
no effect on ability to concentrate urine |
|
|
Term
K+-SPARING DIURETICS
drug names
site of action
mechanism
major effects |
|
Definition
SPIRONOLACTONE, EPLERENONE, AMILORIDE, TRIAMTERENE
late distal tubule & collecting duct
inhibition of Na+ reabsorption
Inhibition of K+ secretion
inhibition of H+ secretion
i/c Na+ excretion (small effect)
d/c K+ excretion (used in combo with loop or thiazide diuretics)
d/c H+ excretion |
|
|
Term
| Factors that promote Na+ reabsorption |
|
Definition
Renal sympathetic nerves
- d/c GFR, i/c PT Na+ & H2O reabsorption --> d/c fluid delivery to MD
- direct stimulation of granular cells (beta-adrenergic receptors)
=> i/c renin secretion
Renin/angiotensin system
Aldosterone |
|
|
Term
| Factors that promote Na+ excretion |
|
Definition
ANP, BNP
Urodilatin
Intrarenal prostaglandins |
|
|
Term
| The 3 mechanisms that control renin secretion by granular cells |
|
Definition
1. SYMPATHETIC stimulation of the granular cells
2. TUBULOGLOMERULAR FEEDBACK in response to a drop in GFR
3. ‘INTRARENAL BARORECEPTOR’ function of the granular cells |
|
|
Term
| The 6 actions of angiotensin II |
|
Definition
systemic arteriolar constriction
renal arteriolar constriction: efferent > afferent
Na+ reabsorption: PCT > TAL, CCD
Thirst
ADH secretion from posterior pituitary
Aldosterone secretion from adrenal cortex |
|
|
Term
| Anatomy of ADH synthesis, secretion |
|
Definition
ADH is produced in the supraoptic and paraventricular nuclei
Stored in the posterior pituitary
ADH secretion is under dual control:
- plasma osmolality (osmoreceptors in the hypothalamus and liver); small i/c provokes i/c in ADH secretion
- arterial pressure (baroreceptors in the carotid sinus and aortic arch); must d/c by 10% before ADH i/c
- A large drop in blood volume i/c the sensitivity of the osmoreceptor mechanism; the opposite is seen with a large i/c in blood volume |
|
|
Term
| Estimate of plasma osmolality from blood chemistries |
|
Definition
Plasma solute conc (mOsm/kg H2O) =
(2 x Na+) + (glucose/18) + (BUN/2.8) |
|
|
Term
|
Definition
difference b/t plasma osmolality as estimated using eqn and true plasma osmolality measured with an osmometer
normally < 10 mOsm/kg H2O
When the osmolar gap > 10, there must be an osmotically active substance, not taken into account by the equation, contributing to the total plasma osmolality |
|
|
Term
Hypernatremia:
always associated with ______
usually due to:
Extrarenal water loss: urine output should be ___, circulating ADH should be ___
Renal water loss: _____________ isn't working; cause? |
|
Definition
always associated with hypertonicity
usually due to H2O loss, not Na+ gain
Extrarenal water loss (excessive sweating, diarrhea, vomiting): urine output should be low, circulating ADH should be high
Renal water loss: ADH mechanism for retaining water isn't working; central or nephrogenic diabetes insipidus |
|
|
Term
|
Definition
caused by loss of salt and water in excess of intake
signs:
- orthostatic hypotension
- othostatic tachycardia
- loss of skin turgor
- dry mucous membranes |
|
|
Term
which hormones are elevated during CHF
what are the mechanisms for these neurohormonal changes? |
|
Definition
Cardiac injury -> d/c CO
d/c CO -> atrial distention -> i/c ANP
*ANP* inhibits the effects of i/c SNS, renin, ADH, aldosterone, but this is not enough to offset their Na+-retaining effects
d/c CO -> d/c ECV -> i/c sympathetic outflow
SNS -> d/c GFR, i/c renin, i/c PT Na+ reabsorption
d/c GFR -> i/c renin -> i/c AT-II
*AT-II* -> thirst, i/c ADH, i/c aldosterone, i/c PT Na+ reabsorption -> i/c EC volume
thirst -> i/c H2O intake -> i/c EC volume
*ADH* -> H2O retention -> i/c EC volume
*Aldosterone* -> i/c CD Na+ reabsorption -> i/c EC volume
i/c EC volume -> circulatory congestion -> edema, hyponatremia, and further contributes to d/c CO |
|
|
Term
| Methods for detecting protein in the urine |
|
Definition
Dipstick - sensitive to albumin, will detect proteinuria in which albumin is a major component
- glomerular injury typically causes albuminuria
Sulfosalicylic acid test: detects all proteins |
|
|
Term
| physiological causes of proteinuria |
|
Definition
loss of *charge barrier* (minimal change disease)
loss of *size barrier* (glomerulonephritis)
*tubulointerstitial disease* (PT fails to reabsorb protein)
*protein overload* (multiple myeloma) |
|
|
Term
The 5 factors that affect K+ secretion in collecting duct
the effect of most diuretics on K+ secretion |
|
Definition
Extracellular K+ concentration
Na+ conc in tubular lumen: negative luminal voltage draws K+ into lumen
- most diuretics i/c Na+ and volume delivery to late DT & CD --> i/c K+ secretion
- a low-Na+ diet has the opposite effect
Luminal fluid flow rate: dilution of secreted K+
- as tubular flow rate i/c, K+ secretion i/c
EC pH: K+ and H+ exchange across cell membranes
- higher pH i/c K+ secretion
- d/c pH d/c K+ secretion
Aldosterone: stimulates K+ excretion in DT & collecting duct by increasing the number of K+ channels (luminal membrane) and Na+,K+ ATPase (BL membrane) |
|
|
Term
Disorders of aldosterone secretion
Conn's disease
Addison's disease |
|
Definition
Conn's: HYPERALDOSTERONISM
- tumor in adrenal cortex
- K+ secretion by CD is inappropriately stimulated
=> HYPOKALEMIA
Addison's:
- destruction of adrenals, aldosterone isn't secreted
- d/c K+ secretion in CD
=> HYPERKALEMIA |
|
|
Term
OSMOTIC DIURETICS
drug names
site of action
mechanism
major effects |
|
Definition
mannitol
PCT
inhibit reabsorption of H2O, Na+ |
|
|
Term
| Effect of plasma pH on free [Ca++] |
|
Definition
Plasma pH affects Ca binding to plasma proteins because H competes with Ca for cation binding sites.
Acidemia: i/c plasma free [Ca++] (hypercalcemia)
Alkalemia: d/c plasma free [Ca++] (hypocalcemia) |
|
|
Term
| Plasma Ca++ and PTH, calcitonin, calcitriol (vit D3) |
|
Definition
PTH and calcitonin play opposite roles in regulating bone breakdown (resorption)
PTH activates resorption to release Ca; calcitonin activates bone deposition.
Decreased plasma [Ca++] will i/c PTH and lower calcitonin, while increased plasma [Ca++] does the opposite
PTH i/c plasma [Ca++]:
- activates bone resorption
- activates tubular Ca++ reabsorption
- activates calcitriol synthesis
Calcitriol activates intestinal absorption of dietary Ca++
- potentiates the effects of PTH on bone and the nephron |
|
|
Term
| Innervation of the urinary tract |
|
Definition
SYMPATHETIC - hypoglossal - ureters, bladder, involuntary urethral sphincter - opposes micturition by inhibiting peristalsis (detrusor) in ureter, dampening bladder contractions, and keeping involuntary sphincter contracted
PARASYMPATHETIC - S2-4 "micturition center," pelvic n - ureters, bladder, involuntary urethral sphincter - favors micturition by activating ureteric peristalsis (detrusor), stimulating bladder to contract, and relaxing the internal urethral sphincter
SENSORY - carry info on wall tension from bladder and urethra to micturition center - i/c by bladder filling -> prompts PNS activity - higher centers in brain also receive info from sensory fibers
SOMATIC - pudendal n - micturition center to voluntary urethral sphincter - contract sphincter to prevent voiding, relax when it's time to pee |
|
|
Term
Bladder empties passively
rearrangement of LaPlace's law |
|
Definition
Tension (T = Pr/2) declines as urine is voided
decreased radius maintains intravesical pressure despite d/c tension (P = 2T/r)
this enables bladder to empty to its residual volume (<25% of capacity) |
|
|
Term
|
Definition
damage to sensory fibers from bladder wall
stretch info not transmitted, contractions not initiated
bladder becomes flaccid, filled to capacity; eventually distended, thin-walled |
|
|
Term
|
Definition
damage to both sensory and parasympathetic neurons innervating the bladder
initially: detrusor contractions cease; bladder becomes flaccid, distended
later: detrusor regains spontaneous activity; bladder shrinks, hypertrophies |
|
|
Term
|
Definition
can result from spinal cord injuries that interrupt communication of higher centers in the brain with the micturition center
acute: "spinal shock" suppresses micturition reflex
reflex can recover, although control by brain is lost |
|
|
Term
| Uninhibited neurogenic bladder |
|
Definition
can be caused by partial damage to the spinal cord that interrupts tracts from the brain suppressing micturition, while leaving intact the tracts that promote micturition
micturition is activated by small amounts of urine
detrusor hypertrophies, bladder capacity reduced |
|
|
Term
|
Definition
carbonic acid: H2CO3
H2CO3 <=> CO2 + H2O
removed from body by ventilation |
|
|
Term
|
Definition
non-carbonic, generated metabolically (sulfuric, phosphoric acids)
neutralized by buffers in body fluids
removed by renal excretion |
|
|
Term
| How is H+ secreted in the urine? |
|
Definition
Fixed acids are excreted in the urine in 2 forms:
titratable acids (most prominent is phosphate): conjugate bases accept H+ in lumen
ammonia (generated by tubular epithelium from glutamine) |
|
|
Term
| Mechanism of reabsorption of filtered HCO3- |
|
Definition
tubular fluid: HCO3 + H -> H2CO3 -CA-> H2O + CO2
Carbon dioxide diffuses into the cell
cell: CO2 + H2O -> H2CO3 -CA-> HCO3 + H
HCO3 exits the cell across the BL membrane by cotransport with Na or by electroneutral exchange with Cl
Ultimately dependent on Na+,K+ ATPase
does NOT result in net excretion of H+
80% of filtered HCO3 is reabsorbed in PT, most of remainder in TAL
Saturable |
|
|
Term
| how do the kidneys generate new bicarbonate? |
|
Definition
Excretion of H+ as titratable acid
1. filtered H2PO4 (most imp buffer)
2. excretion of H+ as ammonium
2 NH4 are produced from 1 Gln
2 HCO3 are produced from 1 NH4
(so 1 Gln --> 4 HCO3) |
|
|
Term
how does the body adapt to chronic acidemia?
to alkalemia? |
|
Definition
by increasing its capacity to make ammonia to buffer secreted H+
Patients with chronic acidemia will show increased NH4 in urine
The β-intercalated cells respond to alkalemia by secreting bicarbonate |
|
|
Term
| The 6 factors that control H+ secretion by the tubular epithelium |
|
Definition
1. Intracellular pH: Decreased IC pH in the tubular epithelium increases H+ secretion
2. Arterial PCO2: Increased PCO2 increases CO2 entry into the epithelial cell, combines with water to form carbonic acid, dissociates to release H+ which is available for secretion.
3. Carbonic anhydrase activity: Pharmacological inhibitors of CA can lower H+ secretion.
4. Extracellular K: This effect is due to the basolateral K/H exchange.
5. Na+ reabsorption: Some Na is reabsorbed in exchange for H, and in the collecting duct, Na reabsorption through the Na channels makes the lumen more electronegative, drawing H out.
6. Aldosterone directly stimulates H secretion by the α-intercalated cells. |
|
|
Term
| what metabolic disorder can diuretic abuse cause? how? |
|
Definition
Alkalemia
EC volume contraction -> i/c renin/AT -> i/c aldosterone -> i/c secretion of H+
K+ depletion -> i/c secretion of H+
i/c secretion of H+ -> i/c reabsorption of all filtered HCO3, contribution of new HCO3 to blood -> metabolic alkalosis |
|
|
Term
|
Definition
used for diagnosing cause of *metabolic acidosis*
AG = (Na+) - (Cl- + HCO3-)
Normal AG (8-16): called hyperchloremic metabolic acidosis, because the decrease in bicarbonate due to acid buffering is matched by an increase in chloride anion
high AG: called high-anion gap or ‘gapped’ acidosis, indicating the presence of an unmeasured anion replacing the bicarbonate used for buffering
- E. ELM PARK
ethanol, ethylene glycol, lactic acid, methanol, paraldehyde, aspirin, renal failures, ketone bodies |
|
|
Term
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Definition
UNa/PNa x Pcr/Ucr = (UV)/(GFRxP) |
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Term
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Definition
pH = 6.1 + log [HCO3/(0.03•pCO2)] |
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Term
LOOP DIURETICS
Drug names
site of action
uses
side effects/toxicities
drug interactions
mechanism for K+ loss |
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Definition
Furosemide (*pulmonary edema*), Torsemide
TAL - block active transport of ions (symporter), can promote lots of extensive solute & H2O loss
- can i/c FeNa to ~25%
- excrete *proportional amounts of Na+ and H2O*
edema (MI, CHF, pulmonary edema, ascites, renal failure), hypercalcemia, anion poisoning (with NaCl)
- FUROSEMIDE acutely vasodilate - req's intact kidneys (*PG mediation,* blocked by NSAIDS or removal of the kidneys)
- decreases left ventricular filling pressure
- *happens before significant diuresis begins,* this is why furosemide is good for pulmonary edema
*Hypokalemia* (K+ is lost in CD), hypomagnesemia, hypokalemic metabolic alkalosis, hyperuricemia (gout), *ototoxicity,* hypovolemia
aminoglycosides (ototoxicity), digitalis (related to hypokalemia), sulfonylureas (hyperglycemia), Li (Na+ is preferentially excreted), NSAIDS, thiazides |
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Term
THIAZIDE DIURETICS
Drug names
site of action
uses
side effects/toxicities
mechanism for K+ loss |
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Definition
Chlorothiazide, Hydrochlorothiazide, Chlorthalidone, (Indapamide, Metozalone have weak action in PT)
"diluting segment" in DT - inhibit NaCl symporter
HTN (reduce blood volume, arteriolar relaxation b/c of d/c Na+, reduced responsiveness of arterioles to NE)
nephrogenic diabetes insipidus (excrete more Na+ than H2O --> reduces polydipsia --> reduces polyuria)
Non-emergency edematous states
Hypercalciuria (stimulated PT reabsorption of Ca++)
hypokalemia (digoxin)
hypokalemia metabolic alkalosis
hyperuricemia
*hyponatremia* (you lose more Na+ than H2O, negative CH2O, w/ or w/o hypovolemia)
*ED* |
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Term
K+ SPARING DIURETICS
Drug names
site of action
uses
side effects/toxicities
mechanism for K+ loss |
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Definition
Spironolactine, Eplerenone - Aldo antagonists
Amiloride, Triamterene - inhibit Na+ transport in DT
Collecting duct
used in HTN to offset hypokalemia from loops and thiazides, or hyperaldosteronism
Hyperkalemia (esp with ACE inhibitors, NSAIDS, beta-blockers) - most common when coadministered with K+ supplement!
anti-androgen effect |
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Term
OSMOTIC DIURETICS
Drug names
site of action
uses
side effects/toxicities
mechanism for K+ loss |
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Definition
Mannitol
Given parenterally (poorly absorbed), act at PT
prophylaxis of renal failure
d/c pressure, volume of intraocular fluid and CSF (head injury)
hemodialysis
more excretion of H2O than Na+
transient expansion of ECF volume, hyponatremia - possible cardiac failure/pulmonary edemaheadaches, nausea, vomiting
long-term: hypernatremia, dehydration |
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Term
| If someone's on a loop diuretic, and become refractive to it, what can you give them to i/c diuresis? |
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Definition
| Indapamide, Metolazone (thiazide-like diuretics) |
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