Renal Flashcards
Function of kidneys
- Homeostasis of body water and electrolytes
=> Regulation of ECF volume, osmolarity, pH, concentration of electrolytes - Excretion of waste products and drugs/ metabolites
e.g urea, creatinine, drugs - Metabolism
=> Biotransformation
=> Gluconeogenesis - Endocrine function
=> Regulation of RBC production (via secretion of EPO)
=> 25-OH vit D activation
=> Secretion of renin
Hormones produces within or activated by the kidney
Secreted by kidney:
- Renin
- EPO
- Thrombopoietin
- Urodilatin
Activated by kidney:
- Vit D (calcitriol)
Renal dysfunction
Abnormal function at any part of the nephron (glomerulus, tubules, interstitium); most commonly a reduction in GFR
Factors governing GFR
GFR = 125ml/min (180L/day)
Starling’s forces:
NFP = k(PG - PB) - 𝛔(πG - πB)
PG = Glomerular capillary hydrostatic pressure
PB = Bowman’s capsule hydrostatic pressure
πG = Glomerular capillary oncotic pressure
πB = Bowman’s oncotic pressure, normally 0
Afferent end
NFP = Pc(60) – PB(15) - πc(21) = 24mmHg
Efferent end: lower PC, higher πc due to fluid leaving the capillary, concentrating the remaining protein.
NFP = Pc(58) – PB(15) - πc(33) = 10mmHg
Control of RBF
~1L/min (20% CO)
Autoregulated over MAP 75-150mmHg
RBF = (MAP-CVP)/RVR
Myogenic mechanism
- Incr perfusion pressure stretches afferent arterioles => decr diameter => incr resistance
Tubuloglomerular feedback
- Incr perfusion pressure => incr GFR and incr flow past juxtaglomerular apparatus => incr Na/Cl past macular densa incr movement of these ions into MD cells
=> Adenosine released => afferent arteriole vasoconstriction, contraction of mesangial cells to reduce SA for filtration, inhibits renin release => decr GFR
- Reduced flow has opposite effects => release of NO + prostaglandins => arteriolar vasodilation and incr renin => incr GFR
RAAS
- Renin released in response to decr tubular flow (sensed by MD -> tubuloglomerular feedback), low aff arteriole p, SNS stimulation
- AT-II => vasoconstricts afferent and efferent arteriole, vasoconstricts vascular SM, triggers release of aldosterone from zona glomerulosa of adrenal cortex (incr Na + H2O reabsorption), release of ADH from hypothalamus (incr water reabsorption in CD)
SNS
- Supplies afferent and efferent arterioles -> vasoconstriction
- A1 receptors mainly located on afferent arteriole
Eicosanoids
- PGI2 and PGE2 released with reduced RBF
- Local vasodilatory effect
- Inhibited by NSAIDS => pre-renal AKI
- PGs have more vasodilation effect of afferent arteriole
ANP
- Dilated afferent arteriole and constricts efferent => incr glomerular hydrostatic pressure and thus incr GFR
Sodium reabsorption
Proximal tubule
- Cotransport with amino acids + glucose
- Counter transport with H+ + NH4+
- Dependent on Na/K ATPase for Na gradient to provide energy for cotransport
- Glomerular tubular balance
=> Na reabsorption adjusted to match GFR
=> Ensure constant fraction of Na + H20 reabsorbed irrespective of GFR
Thick ascending LoH
- Na/K/2Cl cotransport
- Na/H counter transporter
DCT
- Na/Cl co-transport
- Na channels
CD
- Na channels in principle cells
Water reabsorption
- Diffusion through cells and tight junctions
=> Majority is paracellular - creates solvent drag - Driven by osmotic gradient
- Thick limb of LoH impermeable to water
- ADH increases water permeability in CD via aquaporins
K+ reabsorption and secretion
K freely filtered with fixed absorption; secretion is the regulatory process. 3 processes - filtration, reabsorption, secretion
Reabsorption:
Proximal tubule
- 65% reabsorbed by passive diffusion mostly via paracellular (2/3) and trans cellular (1/3)
- Na/K ATPase pumps into tubular cell
LoH
- 25% reabsorbed in ascending LoH via Na/K/2Cl co-transporter
- Active Na/K/2Cl co-transport (major)
- Passive paracellular diffusion (minor)
DCT + CD
- Type A intercalated cells of DCT and CD reabsorb K via K/H counter-transporter
Secretion:
- 2 step process (principle cells of late DCT and CCD)
=> Uptake from interstitium via basolateral Na/K ATPase
=> Passive diffusion via apical K+ channels
=> Secrete K via ROMK
- CCD more important than DCT
=> with normal intake, net secretion
=> with low intake/ depletion, net reabsorption
Factors incr K+ excretion
- High tubular flow rates (incr Na+ delivery to principal cells)
- Incr serum K+
- Aldosterone
- Alkalaemia
Factors decr K+ excretion
- AT-II (decr ROMK activity)
- Acidaemia
Cl- reabsorption
- Paracellular and transcellular diffusion - coupled to Na reabsorption
- Absorbed by paracellular passive diffusion and also active transport with organic ions
- CD type B cells
=> Cl/HCO3 counter-transporter
Glucose reabsorption
Freely filtered at the glomerulus
- In proximal tubules via glucose-Na co-transport (secondary active transport)
- Taken up across apical membrane (from urine to cell) by SGLT-2 in most proximal tubules (SGLT-1 in late PCT)
- Then from cell into interstitium via GLUT-2 (facilitated diffusion)
- Has transport maximum - approx 375mg/min
=> appears in urine at 10-12mmol/L and fully saturated at 15mmol/L
Protein reabsorption
- Some albumin is filtered
- Most reabsorbed by tubules (urine protein content 100mg/day)
- Large proteins taken up by endocytosis and broken down by lysosomes to amino acids which diffusion into peritubular capillaries
- Has transport maximum
Urea reabsorption
Small, water soluble, freely filtered. Highly polar, does not permit lipid bilayers.
- 60% of filtered urea reabsorbed
- 50% in prox tubule reabsorbed via passive diffusion (paracellular)
=> This amount secreted back into LoH
=> Half is reabsorbed in medullary CD - 10% in inner medullary CD
- LoH, DCT, CCD impermeable to urea
=> Net half filtered load is excreted
Regulation of acid base balance
Three mechanisms
Secretion of H+ associated with reabsorption of HCO3-
Excretion of titratable acidity
- Amount of NaOH required to titrate urine to pH 7.4
- Equal to the H+ ions bound to filtered buffers in urine
Excretion of ammonium
Net acid excretion = titratable acid excreted + NH4 excreted - HCO3 excreted
Countercurrent multiplier and exchange
Countercurrent multiplier
- Formed from LoH + CD
- Driven by removal of NaCl from ascending limb
- NaCl actively transported out of thick ascending LoH, incr interstitial osmolality at that level
- Incr osmolality => water reabsorption from descending limb, increasing tubular osmolality at that level
- More concentrated tubular fluid then flows to a deeper, more concentrated level and more water reabsorbed
- Effect is progressive concentration of tubular and interstitial fluid with low and stable energy cost
- End result = dilute urine leaving ascending limb, and highly conc medullary interstitial
Countercurrent exchange
- Vasa recta - peritubular capillaries
- Surround LoH of juxtamedullary nephrons
- Follow the loop into medulla
- Low blood flow - prevents washout of countercurrent multiplier, as slow flow allows solute concentrations to equalise at each level of the loop
- In hypovolaemia, RBF falls and vasa recta flow decr, further reducing washout
- RBF high - flow incr, reduces conc ability of kidney
Glomerulotubular balance
Fixed proportion (not amount) of glomerular filtrate is reabsorbed by proximal tubule.
- Prevents overwhelming of LoH and distal nephron
