Renal and Kidney Function

organs of the human urinary tract

• kidneys

• ureter

• bladder

• urethra

kidney functions (8)

• electrolyte regulation

  • anions/cations

• pH regulation

  • secrete H+ into urine

  • return of HCO3 to blood

• blood volume regulation

  • conserve/eliminate water

• blood pressure regulation

  • conserve/eliminate Na+

• blood osmolarity maintenance

  • blood solute concentration

• hormone production

  • calcitriol = increase Ca+ levels

  • erthropoitetin = increase RBC production

• waste excretion

  • ammonia, bilirubin, creatinine, urea, uric acid

• drug elimination

  • P450 and phase 2 enzymes

where is kidney located? which kidney is higher and why?

• tucked under lower rib cage; positioned at the back

• left kidney higher due to blood flow

ureter function

transport urine from kidneys to bladder

bladder function

stores urine

urethra

transport urine from bladder out of body

kidney blood flow

• abdominal aorta → renal arteries → afferent arterioles

  • afferent arterioles = carry blood into glomerulus (gets filtered)

• efferent arterioles carry filtered blood → wrap around nephron (due to reabsorption) → back to renal vein

what happens if efferent arteriole vasodilates and relaxes?

glomerulus pressure drops

— in glomerulus is critical to what is getting filtered

pressure

Juxtaglmoerular apparatus and renin release

• BP monitored by stretch receptors in juxtaglomerular apparatus

  • low BP → renin released

• Na+ concentration in tubular lumen monitored by cells of macula densa (part of juxta)

  • low Na+ → PGE2 release → stimulate juxta cells → release renin

which med reduces communication between tubule and BP by blocking PGE2?

NSAIDs

RAAS

• what it stands for

• process

• angiotensin II function

• renin-angiotensin-aldosterone system

• process

  • renin acts on angiotensinogen → form angiotensin I

  • ACE converts angiotensin I → angiotensin II

• angiotensin II

  • vasoconstriction (increase BP)

  • stimulate aldosterone → increase na+ and water retention by kidneys (increase BP)

  • overall effect: increase BP and volume

renal capsule

fibrous outer cover of kidney

renal cortex

• below the capsule

• 90% of renal blood flow goes here (highly prefused)

• glomeruli located here

renal medulla

• inner region

• extends to renal pelvis

• 10% of renal blood flow here

glomerulus (blood filter)

• cells/membranes

• porous endothelial cells

  • lines glomerulus capillaries

  • basement membrane

    • later between endothelial cells and podocytes

  • podocytes

    • epithelial cells that wrap around capillaries, forming filtrations between spaces/slits

glomerulus (blood filter)

• charge

• size

• charge selective

• size selection

  • water, ions, glucose, amino acids

  • PREVENT large molecules (proteins, RBCs)

glomerulus (blood filter)

• afferent arteriole

• efferent arteriole

• afferent arteriole → blood enters glomerulus → high hydrostatic pressure (due to narrow efferent arteriole) filters blood

  • filtrate (small molecules) → Bowman’s space → PCT

  • large molecules stay in blood → efferent arteriole

functional unit of kidney?

nephron

2 types of nephron

• cortical

  • 85% of nephrons

  • blood filtration and routine waste removal

• juxtamedullary

  • 15% of nephrons

  • osmotic gradient → concentrate urine and conserve water

main function of PCT

• bulk

what gradient does PCT reabsoprtion depend on?

• Na+ gradient using Na+/K+/ATPase pump

• pumps Na+ out of tubular cell towards blood and K+ into cell

what percentage of filtered HCO3- is reabsorbed in PCT?

80 - 85%

which transporter allows Na+ to enter PCT cell while secreting H+ into lumen?

NHE3

what happens when H+ combines with filtered HCO3- in the lumen?

forms H2CO3 (carbonic acid)

what does H2CO3 (carbonic acid) break down into and how?

CO2 + H2O via luminal carbonic anhydrase IV

Where does CO2 go and what happens?

CO2 enters tubule cell and combines with H2O to form H2CO3 (carbonic acid)

what does H2CO3 in the cell break down into?

H+ and HCO3- via cytoplasmic carbonic anhydrase II

How does the new HCO3- leave the tubular cell?

NBC cotransporter into the blood

which transporters are responsible for glucose reabsorption in PCT? which reabsorbs 90% of filtered glucose?

• SGLT1 ands SGLT2

• SGLT2 reabsorbs 90%

• SGL1 reabsorbs 10%

location and characterisitics of SGLT2

• early PCT

• low affinity and high capacity

location and characterisitics of SGLT1

• late PCT

• high affinity and low capacity

how does glucose enter tubular cell through SGLT? which transporter moves glucose from tubular cell into blood?

• Na+ and glucose move together

• GLUT2

what happens when blood glucose exceeds 180 mg/dL?

SGLT transport capacity exceeded → glucose not reabsorbed → glucose remains in lumen and appears in urine (glycosuria)

loop of henle — thin descending tubule

• T or F: permeable to water

• which aquaporin is present?

• how does water move out of thin descending tubule?

• why does water leave?

• as water leaves, what happens to tubular fluid?

• true → highly permeable → water reabsorption occurs

• AQP1

• passively through osmosis

• it descends into hyperosmotic, highly concentrated medulla

• becomes more concentrated

loop of henle — thin ascending tubule

• T or F: permeable to water

• why is there is no water reabsorption?

• how are Na+ and Cl- reabsorbed?

• what happens to tubular fluid as it moves up the tubule?

• key concept?

• False → not permeable to water → no water reabsorption

• no aqauporins

• passively from tubule into medullary intersititum

• becomes less concentrated (more diluted)

• salt leaves, but water stays

loop of henle — thick ascending tubule

• T or F: permeable to water

• which transporter reabsorbs Na+, K+, 2Cl-? where to?

• what happens to K+ after entering tubular cell?

• which electrical potential does K+ recycling create?

• how does Na+ leave tubular cell towards interstitium?

• how does Cl- leave tubular cell towards interstitium?

• False → not permeable to water → no water reabsorption

• NKCC2 moves them from tubular lumen into tubular cell

• K+ moves back into lumen thru K+ channel

• lumen positive potential

• Na+/K+/ATPase

• Cl- channel

distal tubule

• transporter that reaborbs Na+ and Cl-

• percentage of filtered NaCl reabsorbed?

• which hormone promotes Ca+ reabsorption? transporters used?

• which direction does Ca2+ move during reabsorption?

• what other ion is reabsorbed?

• what happens to filtrate as it passes thru distal tubule?

• NCC

• 5-10%

• PTH; Na/Ca exchanger and Ca2+-ATPase

• tubule → tubular cell → surrounding tissue → blood

• Mg2+

• becomes more diluted

final site for water reabsorption?

collecting duct

what hormone promotes water reabsorption in collecting tubule?

ADH (antidiuretic hormone) = conserves water by preventing excessive water loss in urine

water permeability without ADH

low → water stays in urine → diluted urine

water permeability with ADH

increased → water reabsorbed → urine becomes concentrated

which receptor does ADH activate?

V2 receptor → cAMP increases → AQP2 inserted into membrane → water moves from urine into tubular cell via AQP3 and AQP4

which channel reabsorbs Na+ in collecting tubule?

ENaC (Na+ from urine → back to body)

what pump drives both Na+ reabsorption and K+ secretion?

Na+/K+/ATPase

which channel secretes K+ into urine?

ROMK

what hormone increases ENaC, and Na+/K+/ATPase expression?

aldosterone

excretory function of kidney

regulate excretion of water, electrolytes, urea, drugs, and toxins by filtration, secretion, reabsorption

endocrine function of kidney

• secrete renin and erythropooeitin

• make prostaglandins

metabolic functions of kidney

• acivate vitamin D

• gluconeogenesis

• metabolize insulin and drugs

what is the overall index of kidney function?

GFR

most widely used biomarker of kidney function?

serum creatinine

serum creatinine is a breakdown product of

creatinine from muscle metabolism

creatinine eliminated by kidney thru

filtration at glomerulus + secretion by PCT

as kidney function declines, serum creatinine —-

rises

why does SCr overestimate GFR?

10% of creatinine is secreted by PCT in addtion to being filtered

what happens to SCr with high muscle mass or intense exercise?

SCr increased even if GFR is unchanged

which dietary factors increase Scr?

meat and creatinine intake

what factors can lower SCr and mask reduced GFR?

• low muscle mass

• amputation

• cachexia

• malnutrition

• aging

• liver disease

why is SCr unreliable in AKI?

SCr lags behind true decline in GFR about 1 - 2 days

which drugs block tubular creatinine secretion and falsely increase SCr

• Cimetidine

• triemthoprim

• cobicistat

• dolutegravir

• amiodarone

in adult ≥ 65 years old with SCr < 0.8 mg/dL, what should you do for CG equation?

round SCr up to 0.8 mg/dL

advatnage of Cystatin C over SCr?

production is not affected by muscle mass, diet, activity

what factors can confound cystatin C?

• obesity

• thyroid disease

• high dose steriods

• malignancy

• smoking

• inflammtion

when should combined cystatin c and creatinine equation be considered?

when SCr alone is unreliable

end product of protein/ammonia metabolism in liver?

urea

normal BUN range

5 - 23 mg/dL

BUN:SCr ratio suggests prerenal cause?

20:1

• dehydration

• volume depletion

urine albumin-to-creatinine ratio (UACR)

• meaures?

• uses creatinine for?

• indication

• measures albuminuria using spot urine sample

• uses creatinine to correct urine dilution

• indicates kidney damage and risk for CKD and CVD

GFR

• represents

• best index/gold standard for kidney function?

• tradition gold-standard substance for measuring GFR? why?

• modern tracer used to measure GFR?

• limitations

• measured GFR used for?

• amount of plasma filtered by kidneys per unit time

• yes

• inulin — 100% filtered

• iohexol

• demanding, slow, costly

• research and critical evaluation

CrCl

• estimates what?

• obtained thru?

• what happens if 24-hr urine collection is incomplete or inaccurate?

• which CKD stages is CrCl used?

• kidney function/GFR

• inaccurate and may overestimate true GFR

• stages 4 - 5

CG equation

• purpose

• elderly rule

• renal drug dosing

• age ≥ 65 and SCr < 0.8 → round SCr to 0.8

shwartz equation

• for children

do not estimate GFR infants < 1 week due to nonsteady SCr and maternal creatinine influence

underdosing lead to

• treatment failure

• persistent infection

• thrombus progression

• seizures

overdosing leads to

• nephrotoxicity

• bleeding

• drug accumulation

loading dose

• depend on Vd

• no change for renal impairment

maintenance dose

• depend on elimination

• reduce dose or extend dosing interval or both

NO renal adjustment meds

• antibiotics

• fluoroquinolones

• antimicrobials

• anticoagulants

• opioids

• diabetes

• cardiac

• GI

• ceftriaxone, nafcillin, dicloxacillin

• moxiflocacin

• azithromycin, doxycycline, clindamycin, linezolid

• warfarin, UFH

• fentanyl, methadone

• linagliptin

• metoprolol, carvedilol

• PPIs

in liver disease, SCr drops due to

• reduced muscle mass

• protein-poor diet

• decreased hepatic creatinine synthesis

preferred estimator in cirrhosis

CKD-EPIcr-cys-C

hepatorenal syndrome

rapid kidney failure occuring in cirrhosis

T or F: CKD-EPI and CG equation valid during AKI

false

what clinical measurement is more reliable than SCr in AKI?

urine output

urine output goal in AKI?

less than 0.5 mL/kg/hr

oliguria

low urine output and an early sign of AKI

sarcopenia trap

age related muscle mass lowers SCr, making kidney dunction appear better than it actually is