Renal Physiology

CT1 Education Series (Intro)

R McKee

Renal Physiology• Removal: fluid, electrolytes, metabolic waste (tight control)• Significant blood flow: 20% of CO = 400 ml/100g/min = 1-1.2 l/min

Renal Physiology

• Nephron– Functional unit– From Bowman’s capsule to

collecting duct– 2 types

• Cortical (superficial)– Majority

• Juxtamedullary– Longer LoH

Renal Physiology• Massive concentrating ability - GFR 120 ml/min => Urine 1 ml/min• 2 main processes

– Filtration [Bowman’s capsule]– Reabsorption [Everywhere else]

• Water tends to follow Na+ [Na transport central]

Renal Physiology• Proximal convuluted tubule

– 70% filtered Na reabsorbed– Active & Iso-osmotic - Volume reduction only

Renal Physiology• Loop of Henle

– Active Na reabsorption only in Thick ascending limb• Water impermeable• Rise in medullary osmolality

Renal Physiology• Loop of Henle

– Descending limb can lose water and ions• Concentrated and dehydrated

– Fluid in ascending limb becomes dilute• Na loss

Renal Physiology• Distal convuluted

tubule– Remaining Na

reabsorption• Aldosterone

Renal Physiology• DCT and Collecting

Duct– Water reabsorption

• Passage through medulla

• Final urine concentration

• ADH control

Renal Physiology• Glomerular blood supply

– Afferent from renal artery– Efferent draining glomerular

capillaries

• Dual arterial system allows tight autoregulation across glomerulus

– Afferent dilation following systemic hypotension allows blood flow to remain high

– Filtration can continue

Renal Physiology• Renal blood supply

– Peritubular capillary network (vasa recta)

• From efferent arteriole• Surrounds tubules and

LoH• Excellent concentrating

ability• Significant tubular

energy consumption

Renal Physiology

• Renal blood supply– Glomerular filtration is not energy-intensive– Most energy (and O2) use in the kidney is for

Na/K/ATPase active pumps: Na reabsorption• Mainly in thick ascending limb of LoH

Renal Physiology• Blood flow to nephron

– Hairpin-bend arrangement– Highest O2 consumption in outer medulla

• Blood leaving capillary bed hypoxic• O2 tends to leave capillaries on entering to diffuse across (close apposition)

– Medulla therefore hypoxic• Of most concern in outer medulla

Renal Physiology

• Problems– Highest energy consumption in area with relative hypoxia– Hypotension

• Glomerular filtration hydrostatic pressure initially maintained: afferents dilate (flow remains)

• Blood flow still relatively maintained to outer medulla– Allows concentration to continue

• Feedback mechanism reduces glomerular filtration – Reduces energy expenditure by medulla– Reduces Na loss

Renal PhysiologyGlomerular blood flow• If autoregulation fails…

– <70mmHg– Flow becomes pressure

dependant– Filtration therefore falls…– And if GFR falls, then less

can be excreted.

Renal Failure

• So…– Renal failure often the effect of distant

processes– “Innocent bystander”

• But…– Early intervention can reduce likelihood

Renal Failure

• What is it?– Sudden (usually) reversible failure of kidneys to

excrete nitrogenous and other waste– Multiple definitions– Now: ADQI

• Review evidence• Set research agenda• Make management recommendationsIn acute renal failure, and use of renal replacement

RIFLE Criteria

What causes acute renal failure?

Silvester, Bellomo et al Crit Care Med 2001:29;10

Renal Failure• Vast majority: poor renal perfusion

– Cardiac output/blood pressure• Hypovolaemia• Other low CO states (e.g. cardiogenic shock)• Low SVR (e.g. sepsis)

– Large vessel obstruction• Aortic thrombus/dissection• Renal artery obstruction

– Intra-renal haemodynamics (autoregulation)• Prolonged hypotension• Sepsis• Drugs• obstruction

Renal Failure

• Co-morbidities leading to reduced reserve– CKD– Diabetes– Heart failure– Obstructive uropathy– Liver diseaseMore vulnerable to insult

Renal Failure

• In ICU…– Co-morbidities– Medications

• Antihypertensives => Hypotension• Beta blockers => Hypotension• ACE inhibitors => Hypotension• Duiretics => Hypovolaemia• NSAIDs => loss of autoregulation

Renal Failure

• Does renal failure matter?– Acceptable casualty??– Another organ failure??

Renal Failure

• Renal failure is an independent risk factor for mortality– Levy et al (1996): similar illness severity

with renal failure-up to x6.5 risk of death– CCMed (2002): similar disease severity

and renal failure x2 mortality of those without renal failure

Renal Failure

• Balancing– Optimal support for all organ systems– Overall patient supportMeans kidneys sometimes do suffer

Remember this is not benign!

Urine Acidification

• PCT: Na-H exchange– Na-K-ATPase

• Catalysed by Carbonic Anhydrase

• DCT/CD: H loss independent of Na in tubular lumen– ATP driven proton pump

• Stimulated by aldosterone

Urine Acidification

• Maximum gradient against which transport mechanisms can secrete corresponds to urine pH 4.5

• Buffers allow more H secretionH+ + HCO3

- H2CO3 (C. Anhydrase: PCT only)

H+ + HPO42- H2PO4

- (DCT / CD)

H+ + NH3 NH4+ (PCT and DCT)

• Carbonic anhydrase is in PCT– Allows formation of CO2 and H2O in tubular

fluid• CO2 diffuses across membranes, becoming

available to form H2CO3

• Since most of H+ removed from tubule, pH of fluid changes little

Drug Effects

• Alcohol: inhibits vasopressin• Caffeine: inhibits vasopressin• CA inhibitors: decrease H secretion; resultant rise in

Na and K loss• Metolazone, thiazides: Inhibit Na-Cl cotransport in

early DCT• Loops: inhibit Na-K-2Cl cotransporter in medullary

thick ascending LoH• K-sparing naturietics: inhibit Na-K exchange in CD by

inhibiting aldosterone