Unit 10 - Kidney pt 1 Flashcards
functional unit of the kidney
nephron
what is contained in the renal cortex
- glomerulus
- bowman’s capsule
- proximal tubules
- distal tubules
where are the kidneys located
in the retroperitoneal space between the levels of T12 and L3
the right kidney is slightly more caudal to accommodate the liver
what sections is the kidney divided into
renal cortex - outer section
renal medulla - inner section
what is contained in the renal medulla
loops of Henle
collecting ducts
what are renal papilla and what do they do
the apex of each pyramid
contains collecting ducts, drain urine unto minor calyces
how is urine emptied into ureter
via renal pelvis
formed by multiple major calyces converging
controls extracellular fluid volume
aldosterone
water & Na+ absorbed together
controls plasma osmolarity
ADH
water absorbed, Na+ is not
how is long-term BP control carried out
thirst mechanism (intake)
sodium and water excretion (output)
how is intermediate-term BP control carried out
renin-angiotensin-aldosterone system
responsible for short-term BP control
baroreceptor reflex
primary regulators of acid-base balance
lungs
kidneys
how do the kidneys maintain acid-base balance
by titrating hydrogen in the tubular fluid, which creates acidic or basic urine
where is renin produced
juxtaglomerular apparatus
where is erythropoietin synthesized
in the kidney
secreted in response to hypoxia
how is the bone marrow stimulated to produce erythrocytes
erythropoietin stimulates stem cells in bone marrow
how do prostaglandins affect the renal arteries
PGE2 and PGI2 vasodilate the renal arteries
6 major functions of kidneys
- maintain ECF volume & composition
- long and intermediate BP regulation
- excretion of toxins/metabolites
- maintain acid-base balance
- hormone production
- blood glucose homeostasis
examples of times the kidneys might release EPO
- anemia
- reduced intravascular volume
- hypoxia (high altitude, cardiac and pulmonary failure)
why are patients with severe kidney disease often anemic
severe kidney disease reduces EPO production and leads to chronic anemia
what is the inactive form of vitamin D3
calciferol - vitamin D3
when is calciferol synthesized
during exposure to ultraviolet light
how is calciferol converted to active vitamin D3
converted to 25-hydroxycholecalciferol in liver → converted to calcitriol in kidney
hormone that regulates serum level of calcitriol
PTH
hormone that regulates serum level of calcitriol
PTH
negative feedback
3 ways calcitriol affects serum Calcium
1) Stimulates intestine to absorb Ca2+ from food (↑ serum Ca2+concentration)
2) Instructs kidneys to reduce Ca2+ and phosphate excretion (↑ serum Ca2+)
3) Increases the deposition of Ca2+ into the bone → resorption of “old” bone → increases the serum Ca2+ concentration → helps bone turnover over time
how do kidneys contribute to blood glucose homeostasis
Kidneys can synthesize glucose from amino acids, preventing hypoglycemia during fasting
3 hormones produced by the kidneys
- erythropoietin
- prostaglandins
- calcitriol
how much of CO do kidneys receive
20-25% of CO
(1,000-1,250 mL/min)
renal blood flow calculation
(MAP – Renal venous pressure) / renal vascular resistance
RBF received by renal cortex vs renal medulla
cortex receives 90%
medulla receives 10%
PO2 in renal cortex vs medulla
cortex - 50 mmHg
medulla - 10 mmHg
why is the renal medulla more sensitive to ischemia vs. renal cortex
lower PO2
how is RBF affected by aging
decreases 10% per decade of life after age 50
In the neonate, RBF doubles in the first two weeks of life and achieves an adult level by 2 yrs
order of renal blood flow
afferent arteriole → glomerular capillary bed → efferent arteriole → peritubular capillary bed
how much of the blood delivered to kidney is filtered at the glomerulus
20%
what happens to the blood that is filtered at the glomerulus
after filtration, 99% is reabsorbed into peritubular capillaries
the 1% that isn’t absorbed is excreted as urine
20% of blood delivered to kidney is filtered at glomerulus. where does the other 80% go
circulates through peritubular capillaries
how does blood in peritubular capillaries return to IVC
renal veins
RBF is directly proportional to:
difference between MAP and renal venous pressure
RBF is inversely proportional to
renal vascular resistance
purpose of renal autoregulation
ensure a constant amount of blood flow is delivered to the kidneys over a wide range of arterial blood pressures
what happens to GFR when MAP is outside of autoregulation range
becomes dependent on BP
how does autoregulation control RBF when renal perfusion is too high or too low
- too high: decreases RBF by increasing renal vascular resistance
- too low: increases RBF by decreasing renal vascular resistance
is UOP autoregulated?
NO - it’s linearly related to MAP > 50
6 key contributors to renal autoregulation
- myogenic mechanism
- tubuloglomerular feedback
- RAAS
- ANP
- prostaglandins
- ANS tone
how does the myogenic mechanism respond to renal artery pressure
- pressure elevated = constricts afferent arteriole to protect glomerulus
- pressure low = dilates afferent arteriole to increase blood flow to nephron
where is the juxtaglomerular apparatus located
in the distal tubule, specifically the region that passes between the afferent and efferent arterioles
how do the kidneys receive SNS innervation
T8-L1
how does the surgical stress response affect kidneys
- induces a transient state of vasoconstriction and sodium retention
- This altered physiology persists for several days, leading to oliguria and edema
what renal structures are innervated by SNS
afferent and efferent arterioles
Key monitor of renal perfusion and ultrafiltrate solute concentration (Na+ & Cl-)
Juxtaglomerular Apparatus
where is the Juxtaglomerular Apparatus located
distal tubule
the Juxtaglomerular Apparatus plays a vital role in:
regulating RBF and GFR
how does the Juxtaglomerular Apparatus respond to decreased renal perfusion
releases renin into systemic circulation
3 factors that increase renin output
- SNS activation (beta 1 stimulation)
- decreased renal perfusion (hypovolemia)
- decreased Na+ and Cl- delivery to distal tubule (tubuloglomerular feedback
how is GFR affected by RBF
when RBF decreases, GFR also declines
how can PEEP affect renin
reduces venous return, may reduce CO
reduces renal perfusion and stimualtes renin release
function of juxtaglomerular apparatus
- monitors renal perfusion
- monitors solute concentration
how does the juxtaglomerular apparatus maintain GFR
by modulating renal vascular resistance and renin release
senses decreased Na+ and Cl- delivery to juxtaglomerular apparatus
macula densa
how does AT2 affect GFR
constricts efferent arteriole, which increases GFR
where is angiotensinogen produced
liver
required to convert angiotensinogen to angiotensin I
renin
how is AT I converted to AT II
when AT I passes through lungs, ACE converts ATI to ATII
why can ACE inhibition manifest as cough, allergy-like symptoms, angioedema, and bronchospasm
ACE is involved in bradykinin metabolism
5 ways ATII affects BP
- Among most powerful vasoconstrictors in the body (↑ arterial & venous tone)
- Stimulates aldosterone synthesis in zone glomerulosa of adrenal cortex
- Contributes to SNS activation by increasing catecholamine output from adrenal medulla
- Increased ADH output from posterior pituitary gland
- Increased thirst
where is aldosterone produced
zona glomerulosa of adrenal gland
functions of aldosterone in distal tubule & collecting ducts
- Facilitates Na+ and water reabsorption
- Facilitates H+ and K+ excretion
- Increased extracellular fluid volume = ↑ CO and BP
how does ATII contribute to SNS activation
by increasing catecholamine output from adrenal medulla
causes of decreased renal perfusion pressure that increase renin release
- Hemorrhage
- PEEP
- CHF
- Liver failure w/ ascites
- Sepsis
- Diuresis
where is aldosterone produced
zona glomerulosa of adrenal gland
functions of aldosterone
Facilitates Na+ and water reabsorption and K+ and H+ excretion by stimulating Na/K-ATPase in principal cells of distal tubules
how does aldosterone affect serum osmolarity
Does not meaningfully change serum osmolarity
3 ways aldosterone release can be stimulated
- RAAS activation
- hyperkalemia
- hyponatremia
effects of ATII vs. aldosterone
- Na+ retaining effect of ATII almost immediate
- 1-2 hour delay between aldosterone release and physiologic effects
Conn’s disease
excess aldosterone production → causes Na+ retention & K+ loss
Addison’s disease
usually result of adrenocortical insufficiency (destruction of all of cortical zones)
stimulation of which adrenergic receptor increases renin release
beta 1
monitors of Na+ concentration in ECF
Osmoreceptors
principal determinant of osmolarity
Na+ concentration
Also affected by glucose and BUN
principal determinant of osmolarity
Na+ concentration
Also affected by glucose and BUN
where is ADH mostly produced
supraoptic nuclei of hypothalamus
where is ADH released
posterior pituitary gland
2 mechanisms that control ADH release
- increased osmolarity of ECF
- decreased blood volume
how does increased ECF osmolarity affect ADH release
- ↑ ECF Na+ concentration shrinks osmoreceptors in hypothalamus
- Initiates process of transporting ADH from hypothalamus to posterior pituitary gland
- Thirst reflex activated and antidiuresis prevents additional water loss
how does decreased blood volume control ADH release
Unloading of baroreceptors in carotid sinuses, transverse aortic arch, great veins, and RA stimulate ADH release
2 ways ADH restores BP
- V1 stimulation causes vasoconstriction in vasculature
- V2 stimulation in collecting ducts causes water retention
how does V1 activation cause vasoconstriction
↑ IP3, DAG & Ca2+)
half life of ADH
5-15 min
how do anesthetic agents affect ADH release
don’t directly affect ADH homeostasis but do impact arterial BP and venous blood volume, in turn increasing ADH release
how does V2 stimulation help restore BP
- increased cAMP
- aquaporin-2 channels facilitate water reabsorption, reduces plasma osmolarity, and increases urine osmolality
Net result is expansion of plasma volume
net result of V2 stimulation by ADH
expansion of plasma volume
what causes posterior pituitary to release ADH systemically? (2)
- increased osmolarity of ECF
- decreased blood volume
3 pathways that promote renal vasodilation
1) prostaglandins
2) natriuretic peptide
3) dopamine receptors
where are prostaglandins produced
afferent arteriole
how do prostaglandins play an important role in renal protection
by promoting RBF
what stimulates arachidonic acid liberation from cell membrane
- ischemia
- hypotension
- NE
- AT2
why can NSAIDs reduce RBF
they inihibit cyclooxygenase → can reduce RBF by inhibiting production of vasodilating prostaglandins
pathway that favors production of venal vasoconstrictors under hypoxic conditions
cyclic endoperoxide pathway
how does endotoxin affect renal vasculature
increases leukotriene production, which leads to renal vasoconstriction
how do prostaglandins & natriuretic peptides affect RAAS
- prostaglandins antagonize effects of RAAS
- natriuretic peptides inhibit RAAS
how do ANP & BNP affect BP
inhibit renin release
negative feedback on RAAS = vasodilation, decreased BP
where are dopamine 1 receptors present
renal vasculature, tubules, & splanchnic circulation
2nd messenger for DA1 receptors
increased cAMP
function of DA1 receptors
vasodilation, ↑ RBF, ↑ GFR, diuresis, Na+ excretion (natriuresis)
where are DA2 receptors present
presynaptic adrenergic nerve terminal
2nd messenger of DA2 receptors
decreased cAMP
function of DA2 receptors
decreased norepinephrine release
MAO of fenoldopam
selective DA1 receptor antagonist
low-dose fenoldopam
0.1-0.2 mcg/kg/min
effects of low dose fenoldopam
renal vasodilator and ↑ RBF, GFR, and facilitates Na+ excretion without affecting arterial BP
use of fenoldopam in CV surgery pts
- May offer protection during aortic surgery and CPB
- Reduces requirement for dialysis and in-hospital mortality in cardiac surgery patients
what effect do natriuretic peptides have on the kidneys?
- stimulate sodium & water excretion in collecting ducts
- inhibit renin release
2 components of the nephron
- glomerulus
- renal tubule
where does filtered fluid become urine
renal tubule
forms renal corpuscle
glomerulus & Bowman’s capsule
Where does the initial process of glomerular filtration begin
renal corpuscule
normal GFR
125 mL/min
normal filtration fraction
~20%
(~20% of RBF is filtered by glomerulus & ~80% is delivered to peritubular capillaries)
Glomerular filtrate is identical to plasma except
doesn’t contain plasma proteins, erythrocytes, or WBCs
how are proteins allowed to enter tubules with kidney disease
Kidney disease destroys basement membrane, which allows proteins to enter tubules
driving force that pushes fluid from blood (glomerulus) into Bowman’s capsule
Net filtration pressure (NFP)
NFP calculation
glomerular hydrostatic P – Bowman’s capsule hydrostatic P – glomerular oncotic P
most important determinant of GFR
Glomerular hydrostatic pressure
3 primary determinants of Glomerular hydrostatic pressure
- arterial BP
- afferent arteriole resistance
- efferent arteriole resistance
why do pts with nephrotic syndrome or interstitial nephritis have hypoalbuminemia
they lose proteins in urine
glomulerar filtration depends on:
- RBF
- hydrostatic pressure at Bowman’s capsule
how does constriction of afferent vs efferent arterioles affect GFR
- constriction of efferent increases hydrostatic pressure and GFR
- constriction of afferent decreases RBF and GFR
how does plasma protein concentration affect GFR
increased plasma protein concentration raises plasma oncotic pressure and reduces GFR
what is filtered by glomerular filtration
water, electrolytes, glucose
(proteins are not)
how does BP affect GFR
- increased MAP increases GFR
- decreased MAP decreases GFR
what is reabsorption
process where a substance is transferred from the tubule to the peritubular capillaries
what is secretion
process where a substance is transferred from the peritubular capillaries to the tubule
what is excretion
process where substance is removed from the body in the urine
why might diabetics have glucose in their urine
there’s a max amount that can be reabsorbed into peritubular blood. After max value is achieved, excess substance will be excreted in urine
urine formation is the sum of:
glomerular filtration, tubular reabsorption, and tubular secretion
urinary excretion rate =
filtration – reabsorption + secretion
how does afferent arteriole constriction affect RBF, GFR, and filtration fraction
- RBF: decreased
- GFR: decreased
- filtration fraction: no change
how does efferent arteriole constriction affect RBF, GFR, and filtration fraction
- RBF: decreased
- GFR: increased
- filtration fraction: increased
how does increased plasma protein affect RBF, GFR, and filtration fraction
- RBF: no change
- GFR: decreased
- filtration fraction: decreased
how does decreased plasma protein affect RBF, GFR, and filtration fraction
- RBF: no change
- GFR: increased
- filtration fraction: increased
where does most sodium reabsorption occur in the nephron
proximal tubule
65%
what part of the kidney is responsible for bulk reabsorption of solutes and water
proximal convoluted tubule
how are organic acids, bases, and hydrogen ions secreted into proximal tubule
by Na+ counter transport mechanism
ions that follow Na+ in direct proportion for reabsorption in the proximal tubule
K+
Cl-
bicarb
what % of Na+ reabsorption takes place in the loop of Helne
20%
primary function of descending loop of henle
participate in forming concentrated or dilute urine
separates the handling of Na+ and water
primary function of descending loop of henle
participate in forming concentrated or dilute urine
separates the handling of Na+ and water
part of the kidney responsible for countercurrent mechanisms + high permeability to H2O
descending loop of henle
Ability of kidneys to produce concentrated or dilute urine depends on?
presence of a graduated hyperosmotic peritubular interstitium
2 counterpart systems needed to create and maintain graduated hyperosmotic peritubular interstitium
- loop of henle
- vasa recta
role of loop of Henle in hyperosmotic peritubular interstitium
countercurrent multiplier system that creates osmotic gradient
role of vasa recta in maintaining countercurrent multiplier system that creates osmotic gradient
countercurrent exchanger system that maintains medullary osmotic gradient
where is 20% of water reabsorbed
descending loop of henle
what happens to the osmolarity of peritubular interstitium as the descending limb travels from cortex to medulla
progressively increases - osmolarity starts at 300 mOsm/L and increases to 1500 mOsm/L in renal pelvis
increasing osmolarity provides energy for passively reabsorbing water (osmosis)
what happens to the osmolarity of peritubular interstitium as the descending limb travels from cortex to medulla
progressively increases - osmolarity starts at 300 mOsm/L and increases to 1500 mOsm/L in renal pelvis
increasing osmolarity provides energy for passively reabsorbing water (osmosis)
what are vasa recta
peritubular capillaries that run parallel to loop of Henle
why are vasa recta essential
it returns the reabsorbed water to the blood, allowing osmolarity in peritubular interstitium to remain high
part of the loop of Henle that is not permeable to water
thin & thick segments of the ascending limb
most important pump in Ascending Loop of Henle
Na-K(2)-Cl-co transporter
target of loop diuretics
Na-K(2)-Cl-co transporter in ascending loop of Henle
function of Na-K(2)-Cl-co transporter
removes about 20% of tubular sodium
home to juxtaglomerular apparatus (JGA)
Distal Convoluted Tubule
Key process of the countercurrent multiplier system function of the loop of Henle
Water can’t follow Na+ into peritubular interstitium
tubular fluid becomes more dilute and peritubular interstitium becomes more concentrated
nephrons that play a more important role in countercurrent multiplier
juxtamedullary nephrons play a more signifncant role vs superficial cortical
how is hydrogen excreted in the ascending loop of henle
via sodium-hydrogen exchange mechanism
purpose of countercurrent systems in ascending loop of henle
work together to transfer water from tubular fluid into peritubular interstitium & then return water to blood
without this system, we would produce a ton of dilute urine and cause dehydration
function of distal convoluted tubule
fine tunes solute concentration
2 types of nephrons in kidney
1) superficial cortical
2) juxtamedullary
is the distal tubule permeable to water?
The late distal tubule is impermeable to water except in the presence of aldosterone or ADH
part of the nephron that adjusts urea concentration
distal convoluted tubule
Where do aldosterone & ADH act on the nephron?
distal convoluted tubule
collecting duct
part of the nephron that regulates final concentration of urine
collecting duct
differential when BUN:Cr is increased
dehydration
obstructive uropathy
increased protein intake
upper GI bleeding
why can increased BUN:Cr be due to upper GI bleeding
in the gut, heme is broken down into protein and this protein is metabolized into urea
urea is absorbed into systemic circulation - increases urea load to kidneys
