Renal Hot Topics Flashcards
Erythropoitin
Renin
1,25-dihydroxyvitaminD
renal hormones
ammonia breath – gingival enlargement – xerostomia – tooth problems premature loss narrowing pulp chambers necrosis beneath fillings or crowns
oral health manifestations of renal disease
where does this happen-
blood is filtered in glomeruli and the filtrate passes through tubules of the nephron
renal cortex
where does this happen- there are portions of nephron tubule involved with concentration and collection of urine
renal medulla
which renal process- solutes (and the water they are dissolved in) pass from the blood into the tubular fluid in the renal capsule (Bowman’s space)
-filtration
which renal process- substances are transported from the blood in the peritubular capillaries into the tubular fluid
secretion
which renal process- substances are transported from the tubular fluid into the blood in the peritubular capillaries
reabsorption
a dense capillary bed where filtration occurs
surrounded by renal capsule (or Bowman’s capsule) which collects the filtrate from the blood entering via the afferent arterioles
glomerulus
- smooth muscle contraction in afferent or efferent arterioles
- response of the juxtaglomerular apparatus (JGA) located at the intersection of the macula densa of distal tubule with afferent and efferent arterioles – the JGA secretes the hormone renin which regulates systemic blood pressure
blood flow through glomerulus regulation mechanisms
which part of the nephron- reabsorbs 2/3 of filtered salt and water; reabsorbs all filtered glucose and amino acids; some diuretics will act here
-proximal convoluted tubule
which part of the nephron- is divided into thin descending limb; thin ascending limb; thick ascending limb (TAL
loop of Henle
site of countercurrent multiplication needed to produce concentrated urine, but itself produces a dilute filtrate. Very powerful diuretics work here
loop of Henle
which part of the nephron- continued reabsorption of solutes; regulation of calcium; site of action for some diuretics
-distal convoluted tubule
Which part of the nephron- collects fluid from multiple nephrons; extends from cortex through the medulla; regulates sodium, potassium, and water; some diuretics act here
collecting duct
the volume of plasma from which all of a particular substance is removed to the urine (i.e. cleared), e.g. 100 ml/min; clinically important concept for monitoring renal function
renal clearance
amount of blood filtered by the kidney, expessed as volume per unit time
glomerular filtration rate
small polysaccharide; freely filtered and not secreted or absorbed; used to measure renal clearance
inulin
product of muscle metabolism; freely filtered, not reasbsorbed, almost no secretion; normal levels < 1+ 0.5 mg/dl; if > 10 requires dialysis
creatinine
negative charge
charge of basement membrane
pressure due to fluid
P in capillaries > P in capsule fluid
hydrostatic pressure
pressure due to solutes in fluid (including those not dissolved)
π in capillaries > π in capsule fluid
oncotic pressure
favors filtration from blood into the capsule fluid
net filtration pressure
myogenic mechanism – vascular smooth muscle tends to contract when it is stretched, and relax when not stretched; constriction or dilation of smooth muscle in afferent or efferent arterioles has contrasting effects on RBF
tubuloglomerular feedback – feedback from the JGA adjusts afferent arteriole diameter
autoregulation intrinsic mechanisms; adjust blood flow through the glomerulus
molecules move through tubular cells
transcellular
molecules move between tubular cells
paracellular
results from solutes being carried by water in paracellular transport
rate of water diffusion can be regulated by aquaporins (water channels)
solvent drag
Where is this reabsorption taking place?
- Glucose and amino acids are rebsorbed with Na+ using symporters
- Active transport on basal side, keeps intracellular Na+ low
- Water (and solutes) move via paracellular transport; keeps the osmolarity of the tubular fluid constant
- Na+ reabsorption also occurs in conjunction with bicarbonate reabsorption using a Na+/H+ antiporter
reabsorption in the proximal tubule
Where is this reabsorption taking place?
-indirect reabsorption; CA reaction produces H+ and HCO3- in tubule cell HCO3- is transported into blood H+ transported into tubular fluid where it recombines with a filtered HCO3-
proximal tubule
They are commonly bound to plasma proteins so they are not filtered at the glomerulus, must be secreted in order for them to be excreted in the urine
many drugs that are organic ionic compounds
By the end of this part of the nephron… 2/3 of Na+, Cl-, and water reabsorbed; small proteins too (by endocytosis)
- K+ and divalent cations reabsorbed by solvent drag
- all amino acids and glucose reabsorbed- Na symporters
- bicarbonate reabsorbed due to activity of Na+ / H+ transporter
- secretion of organic ions (drugs) (just know that they don’t get filtered, just get secreted to be removed from body)
proximal tubule
Which part of the loop of Henle? impermeable to salt, but permeable to water
descending thin limb
Which part of the loop of Henle? impermeable to water, but permeable to salt.
ascending thin limb
Which part of the loop of Henle?
- Na+ K+ 2Cl- symporter in apical membrane
- pNa+ K+ ATPase in basolateral membrane
- paracellular transport of monovalents and divalents NOT due to solvent drag. Tubular fluid becomes positive when Cl- reabsorbed so cations diffuse along an electrical gradient
ascending thick limb
Fluid leaving this part is hyposmotic, but the renal countercurrent mechanism has established an osmotic gradient required for formation of hyperosmotic urine
loop of Henle
Concentration of the tubular fluid will occur in the collecting duct if _____ is present
ADH/Vasopressin
are permeable to NaCl and water so ——–osmolarity changes as the capillaries follow the loop, but the osmolarity of the —–leaving the kidney (to veins) is normal.
plasma; blood
Where in the nephron?
-initial segment of these areas reabsorbs ~8% of filtered NaCl via a Na+ Cl- symporter in apical membrane and Na+ K+ ATPase in basolateral membrane
reabsorption of K+, H+ and water is variable
-Sodium reabsorption in the latter half of these areas is similar
-distal tubule and collecting duct
Where in the nephron?
-principal cells have epithelial sodium channels (ENaC) that reabsorb Na+ and secrete K+
(excess K leaves blood and enters tubular fluid)
Na+ reabsorption drives paracellular Cl- reabsorption
the first area will both secrete and absorb K+
K+ secreted due to Na+ K+ ATPase activity in basal membrane
-intercalated cells involved with acid-base balance; can also reabsorb K+
(can also serve to reabsorb K+)
-collecting duct and late distal tubule
- released from the posterior pituitary
- release is stimulated by changes in osmolality of body fluids
- respond to osmolality above a set point of 275-290 mOsm/kg H2O
- release can also be stimulated by changes in blood volume/pressure
ADH/Vasopressin
in left atrium and large pulmonary vessels respond to a decrease in blood volume; respond to decrease in BP; send signal via CN to hypothalamus ADH secretion (function at low pressures)
low pressure baroreceptors
in aortic arch and carotid sinus response to a decrease in blood pressure; still respond to drop in BP; activate ADH secretion and sympathetic nervous system
high pressure baroreceptors
increases the permeability of the late distal tubule and the collecting duct to water by increasing aquaporins into the apical membrane
action of ADH
Which ADH level? diuresis – solutes reabsorbed in distal tubule and collecting duct, but no water reabsorption; urine as dilute as 50 mOsm/kg H2O
low ADH
Which ADH level? (antidiuresis) – water reabsorbed as fluid passes through collecting duct; urine can be concentrated up to 1200 mOsm/kg H2O
high ADH
stimulates events that increase reabsorption of sodium and water (combat volume contraction); this helps to return blood volume to normal
renin-angiotensin-aldosterone system
- released in response to a drop in perfusion pressure, decreased NaCl delivery to macula densa, or sympathetic input to juxtaglomerular cells
- this stimulates secretion of renin from granular cells around capillaries, can also be due to sympathetic input to granular cells
- converts angiotensinogen to angiotensin I
renin
angiotensin I converted to angiotensin II by…
angiotensin converting enzyme
has multiple effects
vasoconstriction- stimulates arterial pressure
-stimulate release of ADH- into posterior pituitary increase water reabsorption
-increase sympathetic activity- act in heart and kidney maintain BP
-stimulate aldosterone secretion- in zona glomerulosa acts in kidney to increase Na reabsorption into blood and K+ secretion into tubular fluid
-angiotensin II
(steroid- regulate protein synthesis; slow acting; long acting; slower than ADH) from the adrenal cortex acts to increase NaCl reabsorption in the distal tubule and collecting duct by increasing transport protein synthesis
aldosterone
are hormones secreted when the heart dilates (during volume expansion); detected primarily through stretch receptors
Natriuretic peptides
effects of ———— include
- vasodilation of afferent arterioles- increase filtration rate, increases Na and H2O filtered
- vasoconstriction of efferent arterioles- increasing filtration pressure
- inhibition of renin (and aldosterone)- decreases Na reabsorption and K secretion
- inhibition of ADH secretion- decreases BV, elimination of excess Na and H2O
- Net effect is to increase the excretion of NaCl and water.
-natriuretic peptides
in proximal tubule- increased volume leads to increased filtration, leads to less
Na reabsorption
increased volume in the thick ascending limb leads to more
Na reabsorption
in the distal tubule- increased volume leads to more
Na reabsorption
in the collecting duct- increased volume leads to
excretion of more Na and H2O
will depolarize Vm
-leads to easier depolarization, hypersensitivity to stimulation, dangerous for end-stage renal
Hyperkalemia
will hyperpolarize Vm
- make inside of cell more negative
- this will lead to suppression of neural and muscle responses (can depress heart function)
- due to vomiting, diarrhea or use of diuretics
hypokalemia
ingested K+ is fast shifted into cells – mediated by ___, ___, ___ gets out of the blood; kidneys typically excrete 90-95% of ingested K+
insulin, epinephrine and aldosterone
- increased K+ stimulates ____ release, and _____increases Na+ K+ ATPases in principal cells
aldosterone; aldosterone
increased ——- increases K+ secretion (cilia monitor this); local response to bending of cilia
flow rate
Which cells in collecting tubule reabsorbs K+
intercalated cells
which cells in collecting tubule secrete K+
principal cells
Which acid is non-titratable?
-NH4+
- decrease body pH by not reabsorbing all HCO3- ; produces an alkaline urine and acidifies body fluids; excretion of HCO3-
- no effect on body pH by reabsorbing all HCO3- ; urine has a neutral pH
- increase body pH by reabsorbing all and producing more HCO3- (typical); produces an acidic urine and alkalinizes body fluids
renal regulation of body pH to produce urine with different pH
HCO3- is not directly transported from tubular fluid into blood so HCO3- production and reabsorption results in ….
H+ secretion
bicarbonate reabsorption begins and 80% of filtered HCO3- is reabsorbed here
proximal tubule
This enzyme’s activity in the tubular epithelium produces H+ and HCO3-
CA
in the proximal tubule H+ is secreted via
Na/H antiporter
HCO3- in the proximal tubules is
transported/reabsorbed across basolateral membrane
Where in the nephron?
-CA activity in the intercalated cells produces H+ and HCO3-
H+ is secreted via an H+ ATPase pumps and an H+/K+ ATPase pump (not illustrated)
secreted H+ can be buffered by HCO3-, HPO4-, or ammonia (NH3)
the last of all filtered HCO3- is reabsorbed
late distal tubule and collecting duct
cells of ______ detect intracellular pH and can alter CA activity accordingly.
proximal tubule
After all HCO3- has been reabsorbed and HPO4- is depleted, the kidney will produce ___ as a third buffer to increase the amount of H+ that can be excreted
ammonium (NH3)
This is possible by what mechanism?
- Much of the NH4+ leaving the proximal tubule is reabsorbed by the ascending limb of the loop of Henle (note that the orientation of the tubule cell is reversed in the proximal tubule diagram below)
- NH4+ substitutes for K+ in the Na+K+2Cl- symporter and enters the interstitial fluid in the medulla where it is in equilibrium with NH3
diffusion trapping
low pH due to CO2 build-up
causes include impaired pulmonary function
renal compensatory response produce new HCO3-
respiratory acidosis
high pH due to low PCO2
causes include hyperventilation, anxiety, altitude, fever, drugs
renal compensatory response excrete HCO3-
respiratory alkalosis
- low pH due to low HCO3-
-causes include diabetic ketosis, diarrhea, renal failure
-respiratory compensatory response hyperventilate; trying to get rid of CO2 source of H+ ions
renal compensatory response produce new HCO3-, depending on cause
metabolic acidosis
- hi pH due to excess HCO3-
- causes include vomiting, antacids, hemorrhage; don’t take tums just because they taste good
- respiratory compensatory response –hypoventilate (how does this work?)- not blowing off as much CO2, some excess remains in blood, forms acid and can neutralize excess base
metabolic alkalosis
- released in response to hypocalcemia
- increases bone resorption, increases renal Ca+ reabsorption, and stimulates calcitriol production
parathyroid hormone
- metabolism of vitamin D to _____is stimulated by hypocalcaemia and/or hypophosphatemia (and further stimulated by PTH, see above)
- stimulates active transport mechanism for Ca2+ absorption in the small intestine
- facilitates action of PTH and increases renal Ca2+ transport
calcitrol (1,25 dihydroxyvitamin D)
- released in response to hypercalcemia
- increases bone deposition
calcitonin
calcium reabsorption in the _____ mostly by paracellular transport/solvent drag
proximal tubule
calcium reabsorption in the ____ – transcellular and paracellular transport (paracellular not solvent drag)
thick ascending limb
calcium reabsorption in the ______ transcellular reabsorption of calcium
transport here can be regulated because expression of Ca2+ transporters is regulated by PTH
distal tubule
excessive urine output
diuresis
what drug to use in CHF and hypertension?
-diuretics
retain water by increasing osmotic pressure; act in water-permeable segments of the nephron (PT & descending loop of Henle)
osmotic diuretics
reduce Na+ reabsorption; proximal tubule is major site of action
CA inhibitors
act in thick ascending limb to inhibit Na+ reabsorption via the Na+ K+ 2Cl- symporter
Loop diuretics
block Na+Cl- symporter in early distal tubule
thiazides
two classes that both act in late distal tubule and cortical collecting duct to inhibit sodium reabsorption AND potassium secretion
- aldosterone antagonists
2. ENaC blockers
– ADH receptor antagonists
aquaretics
Which diuretic is good for this situation?
Examples include mannitol and pathologically elevated glucose.
-gain access to tubule by glomerular filtration
-are poorly reabsorbed
-will have an effect where tubule is freely permeable to water
-some of what’s not reabsorbed in PT and DL can be reabsorbed downstream, but typically results in excretion of 10% of filtered Na+
note: ↓ water reabsorption ↓ Ca2+ reabsorption by solvent drag
-osmotic diuretics
Which diuretic is good for this situation?
- reduce Na+ reabsorption by inhibiting this enzyme, thus reducing the H+ available for the Na+/H+ antiporter. Acetazolamide is an example of this drug.
- _____gain access to the proximal tubule via secretion
- Most of the diuretic effect is in the proximal tubule where ~1/3 of Na+ reabsorption relies on the Na+/H+ antiporter
carbonic anyhydrase inhibitors
are the most powerful of all diuretics; they inhibit Na+ reabsorption in the ascending limb of the loop of Henle. Furosemide (lasix) is an example of this diuretic
- Inhibit Na+K+2Cl- symporter in the thick ascending limb which inhibits Na+ reabsorption
- urine leaving loop is not dilute
- Can increase Na+ excretion to as much as 25% of filtered load, because Na+ reabsorption capacities downstream of their site of action are limited
loop diuretics
- diuretics like chlorothiazide are secreted into the proximal tubules, and they act in the early distal tubule to block the Na+Cl- transporter
- kidney’s ability to dilute urine is diminished
- reabsorption of water in the collecting duct still occurs, but 5-20% of the filtered Na+ is excreted
thiazide diuretics
act where K+ is normally secreted into the tubular fluid by the principal cells. There are two types
K+ sparing diuretics
-aldosterone antagonists, e.g. spironolactone
block aldosterone’s ability to increase Na+ transporters in principal cells
-must get inside tubular cells to block aldosterone receptors
-ENaC blockers, e.g. amiloride
block Na+ reabsorption across the apical membrane
-these act on a membrane protein so can gain access by secretion into the proximal tubule
-K+ sparing diuretics
e.g. tolvaptan, increase excretion of water by blocking the action of ADH in the late distal tubules and collecting duct. Water is eliminated without the loss of solutes
Aquaretics
Continued use of diuretics becomes less effective because volume contraction counteracts the effects of the diuretic, i.e. diuretics decrease ECV so compensatory mechanisms activated
diuretic braking phenomenon
- increased sympathetic activity in response to reduced BP decrease GFR increase PT reabsorption & increase renin
- decrease natriuretic peptides
- secrete renin from juxtaglomerular apparatus increase angiotensin II and aldosterone decrease Na+ excretion
- stimulate ADH release decrease water excretion
diuretic braking phenomenon
Acid-base balance is affected by all diuretics
CA inhibitors
leads to metabolic acidosis
Loop and thiazide diuretics –>reduced ECV –>
metabolic alkalosis
potassium-sparing diuretics –>
metabolic acidosis- because H+ secretion is inhibited
Except for the ____ diuretics, all other diuretics alter calcium excretion
K+ sparing
act in proximal tubule and reduce reabsorption of calcium in this segment (so excretion is increased).
osmotic and CA inhibitors
increase calcium excretion by affecting the transepithelial voltage that normally provides the driving force for paracellular transport of calcium
loop diuretics
stimulate calcium reabsorption in the distal tubule and thus reduce excretion.
Normally, distal tubule reabsorbs 9% of filtered calcium via active transport.
thiazide diuretics
blood is briefly removed from the body to be circulated through a ________, which is a cylindrical bundle of hollow fibers. The walls of the fibers are made of a semipermeable membrane with pores of defined size that allow small molecules to diffuse into the dialysis fluid. The fluid and blood move in countercurrent directions to remove nitrogenous and other wastes, and adjust osmolarity before the blood is returned to the body
dialyzer
used to access venous blood for short-term treatment; scarring, vessel narrowing or occlusion can occur
catheter
preferred for long-term treatment; creates an anastomosis between artery and vein. Arterial blood is withdrawn, and blood is returned to the vein after dialysis.
AV fistula
uses an artificial/synthetic vessel to join an artery and vein when vascular problems do not permit using a fistula; can become narrowed which can lead to clotting and/or infections
AV graft
fatigue, chest pains, cramps, nausea, headaches
- often called “dialysis hangover”
- due to acute, dramatic changes in blood chemistry.
short-term side effect of dialysis
- sepsis, endocarditis & osteomyelitis (secondary infections)
- amyloid deposits in joints (like amyloid plaques that form in neural tissue) can result from the build-up of trace minerals (e.g. copper, zinc, and aluminum) that might be in the dialysis fluid
long-term consequences
Patients with chronic renal failure are almost always diagnosed with anemia due inadequate secretion
erythropoietin
EPO production is stimulated when ____is low due to activity of transcription factors that regulate EPO synthesis
PO2
- are continually produced, but are targeted for degradation when O2 is normal.
- O2 is low, they function as transcription factors to increase EPO synthesis and secretion.
hypoxia-inducible factors 1 and 2 or HIF-1 and HIF-2
anemia typically uses Procrit ® to stimulate
erythropoiesis
flu-like symptoms, headaches, high BP, and cardiovascular problems
side effects of Procrit
