Kidney Function 1 Flashcards
What are the major functions of the kidney?
- water and sodium homeostasis
- acid-base balance
- control of ECF ion concentration (K, Ca, Mg, Cl, HPO4)
- excretion of waste products and xenobiotics
- endocrine secretions (EPO, renin, VitD3, PGI2)
- formation of concentrated (1200mOs/L) or dilute urine (30mOs/L)
What are the features of superficial cortical glomeruli (SCG)?
- 85% of glomeruli
- short LOH; penetrate short distance into medulla
- efferent arterioles give rise to cortical capilaries surrounding PCT & DCT
What are the features of juxtamedullary glomeruli (JMG)?
- 10-15% of glomeruli
- at junction of medulla and cortex
- long LOH; penetrate deeply into medulla to papilla
- efferent arterioles become vasa recta around LOH
- responsible for the concentration gradient of the kidney that allows formation of concentrated urine
- 300mOs at junction
- 1200mOs at papilla
Normal renal blood flow in a 70kg human is
1L/min (total including both kidneys) ~20% of CO
What percentage of cardiac output flows through the renal vasculature per minute?
20%
What is normal haematocrit (packed cell volume)?
(% of RBCs in blood)
40% - women
45% - men
What is filtered from the renal blood flow?
plasma
Renal plasma flow to the kidney is
~600mL/min
Normal glomerular filtration rate (GFR) is
120mL/min (both kidneys)
60mL/min (each kidney)
approximately 180L/day of plasma is filtered
What volume of plasma is filtered per day?
approximately 180L/day of plasma is filtered
Average urine output is
1-2L/day
What is the function of the peritubular capillaries?
- come from efferent arteriole
- surround nephron closely
- take up 178L of 180L of plasma that is filtered per day
- maintains ~1-2L/day urine output
What comprises the juxtaglomerular apparatus (JGA)?
- terminal thick ascending LOH
- afferent and efferent arterioles
- macula densa cells in thich ascending LOH
What is the formula for MAP?
MAP = DP + 1/3(SP - DP)
What is the blood pressure range for which renal autoregulation can function?
70-180mmHg
Glomerular pressure is
constantly ~50mmHg
What are the functional roles of the JGA and macula densa cells?
function in autoregulation and tubuloglomerular feedback
What is tubuloglomerular feedback?
- part of autoregulatory function of glomerulus
- macula densa cells detect NaCl in thich ascending LOH/DT junction
- feedback via paracrine mediators (eg adenosine released from MD cells) to alter tone of afferent (only) arteriole
- adenosine causes vasoconstriction
- other mediators eg prostaglandins cause dilation
What are the two components of autoregulation?
tubuloglomerular feedback and the myogenic reflex
What is the myogenic reflex (renal)?
- afferent arteriole responds to stretch by contracting - it resists change by mitigating the dilating force
- helps maintain glomerular pressure of ~50mmHg
What are the roles of the macula densa?
- functions in tubuloglomerular feedback
- functions in renin release from epithelial cells of the afferent arteriole
- these are independent functions - renin release is NOT involved in tubuloglomerular feedback
What is clearance?
- amount of plasma removed per unit time
- clearance of a specific plasma constituent eg Na is the volume of plasma which is cleared of Na over time
- eg rate of urinary excretion of Na/plasma concentration of Na
- renal clearance = UV/P
- U = urinary concentration of substance
- V = rate of urine, usually per day
- P = plasma concentration
What is excretion?
urine concentration of substance x urine volume
UV
Why is creatinine clearance used to approximate GFR?
- net reabsorbtion and secretion of creatinine are equal
- therefore it is effectively all filtered and all cleared (no reabsorption) and the rate is equal to GFR
What components of the glomerular structure contribute to filtration?
- size restriction (up to ~1000 daltons):
- fenestrations of the capillary inside the glomerulus
- basal lamina
- charge restriction (negatively charged, repel negative charges eg albumin)
- basal lamina
- foot processes of podocytes
Microalbuminuria indicates
- elevated (but small) amounts of albumin in the urine of diabetics (not easily detected in normal urine)
- suggests damage to the basal lamina in the glomerulus
- first stage in advanced/long-standing diabetes is loss of negative charges to repel plasma proteins from being filtered
The filtration fraction of renal plasma flow is
0.2 (~20%)
Hydrostatic pressure in the glomerular capillary is
50mmHg
Hydrostatic pressure in Bowman’s capsule is
10mmHg
Oncotic pressure in the glomerular capillary is
25mmHg
Oncotic pressure in Bowman’s capsule is
~0mmHg (99% of proteins are not filtered)
The driving force of filtation is
15mmHg
Oncotic pressure in the efferent arteriole is
40mmHg
(from proteins remaining while water and solutes are filtered)
What happens to GFR when the afferent arteriole constricts?
GFR decreases because glomerular capillary pressure decreases
What happens to GFR when the efferen arteriole constricts?
GFR increases due to increased glomerular capillary pressure
Angiotensin II acts on which arteriole, to produce what?
- vasoconstriction of the efferent arteriole via Ang II receptors (more pronounced on efferent arteriole)
- increases the filtration fraction
- ACE inhibitors reduce [AngII] tf decrease filtration fraction
Autoregulation occurs at
the afferent arteriole
Renal blood flow =
delta pressure (pressure drop from afferent to efferent)
resistance to flow
Adenosine acts preferentially on
afferent arteriole (vasoconstriction)
Thromboxane acts preferentially on
afferent arteriole (vasoconstriction)
Where is renin released from?
- granular cells that line the afferent arteriole only at junction with entrance to the glomerulus
- these cells replace the normal arteriolar endothelium
What is the role of renin?
increase BP and salt retention
Renin is released in response to
- volume depletion and blood pressure decrease (passive contraction of the afferent arteriole)
- decreased Na sensed by MD cells over a period of time
- mechanism is unknown but is different to TGF (seconds to minutes)
- activation of sympathetic nerves to the kidney
- epi or NE stimualte b1-aRs in JG cells
How much creatinine is normally produced per day?
~10mmol
What is the average plasma concentration of creatinine?
50µmol/L
Creatinine clearance is measured by
24-hour urine collection (~2L)
Normal urine concentration of creatinine is
4.5mmol/L
How much creatinine is excreted per day? Cleared per day?
50µmol/L x 180 L/day = 9000µmol/day = 9mmol/day
(10mmol/day is produced; remaining 1mmol increases plasma concentration until excretion matches production - tf over 180L plasma per day are filtered of creatinine)
How is inulin used to calculate GFR?
- not made by body, must be infused at a constant rate
- completely filtered by glomerulus but neither secreted nor reabsorbed by the tubules
- tf equal to GFR
What is normal glucose clearance?
0; ~900mmol is freely filtered per day but 100% is reabsorbed by secondary active transport
When does glucose appear in the urine?
- glucose beyond normal range of 4-6mmol
- excess overcomes secondary active transport mechanism of reabsorption
- tf not all glucose is reabsorbed and appears in the blood
What is the clearance of penicillin?
- 150mL/min (greater than GFR, 120mL/min)
- penicillin is freely filtered at glomerulus
- not recognized by any transporters in renal tubule tf not reabsorbed
- presence in tubule stimulates secreting systems to secrete penicillin left in the peritubular capillaries into the lumen
- very rapidly excreted
- used to be rx with probenecid to suppress secretion
