Renal physiology 2

Renal Physiology 2Renal Physiology 2

Dr. Bikesh Pandey

Urine formation 1Urine formation 1

Renal Blood SupplyRenal Blood Supply

Renal Blood Supply Renal Blood Supply

Renal blood flow (RBF)Renal blood flow (RBF)

• It is the volume of blood delivered to the kidneys per unit time.

• Kidneys receive roughly 22% of cardiac output.

• Thus, RBF = 1.1 L/min in a 70-kg adult male.

Renal plasma flow (RPF)Renal plasma flow (RPF)

• It is the volume of blood plasma delivered to the kidneys per unit time.

• Since plasma in blood is about 55% , RPF = 605 ml/min

Urine FormationUrine Formation

• Results from :

– Glomerular Filtration

– Tubular Reabsorption

– Tubular Secretion

Excretion Rate of Excretion Rate of different Substancesdifferent Substances

Panel APanel A • Substance is freely filtered by the

glomerular capillaries but is neither reabsorbed nor secreted.

• Excretion rate = Filtration rate

• Eg: Creatinine

Panel BPanel B

• Substance is freely filtered but is also partly reabsorbed from the tubules

• Excretion rate < Filtration rate

• Eg: Most of the electrolytes

Excretion Rate of Excretion Rate of different Substancesdifferent Substances

Panel CPanel C • Substance is freely filtered & is fully

reabsorbed thus is not excreted

• Excretion rate = 0

• Eg: AA and Glucose

Panel DPanel D

• Substance is freely filtered & is not reabsorbed, but additional quantities of this substance are secreted from the peritubular capillary

• Excretion rate = Filtration rate + Secretion rate

• Eg : Organic acids and Bases blood

Urinary space

Slit pores

Glomerular FiltrationGlomerular Filtration• It is the “First Step” in Urine Formation.

• Blood is filtered through Filtration Barrier.Filtration Barrier.

Filtration BarrierFiltration Barrier

• Endothelium

• Basement Membrane

• Filtration slit

Glomerular FiltrationGlomerular Filtration

Glomerular filtration rate (GFR) Glomerular filtration rate (GFR)

• It is the volume of fluid filtered from the glomerular capillaries into the Bowman's capsule per unit time.

• Normal GFR is about 125 ml/min, or 180 L/day

• RPF is 605 ml/min & GFR is 125 ml/min, thus it can be said that GFR is 20% of RPF, suggesting 20% of the plasma is filtered through glomerulus that reaches to kidney.


Importance of High GFRImportance of High GFR

• We know that,

– Entire plasma volume is only about 3 L.

– GFR is about 180 L/day

This means : the entire plasma can be filtered and processed about 60 times each day.

• This is necessary to be able to remove waste products “Rapidly” & “Precisely”.


FilterabilityFilterability

• It is the “Degree of easiness for a substance to cross the glomerulus”

• It is inversely propotional to Molecular weight (MW).

• Negative charged molecules cross less easily than positive charged molecule for same MW, due to the fact that basement membrane and podocytes are also negatively charged.

<> A filterability of 1.0 means that the substance is filtered as freely as water;

<> A filterability of 0.75 means that the substance is filtered only 75 per cent as rapidly as water

Glomerular FiltrationGlomerular FiltrationComposition of the Glomerular FiltrateComposition of the Glomerular Filtrate

• Glomerular filtrate is essentially:

– Devoid of cellular elements like RBC/WBC/PLT and

– Protein-free

• The concentrations of most salts and organic molecules, are similar to the concentrations in the plasma.

– Exceptions include

• Calcium and fatty acids

• Because of the fact that, they are partially bound to the plasma proteins.

• Almost one half of the plasma calcium and most of the plasma fatty acids are bound to proteins, and these bound portions are not filtered through the glomerular capillaries.


(1) Hydrostatic pressure of glomerular capillaries - Promotes filtration

(2) Hydrostatic pressure of Bowman’s capsule - Opposes filtration

Determinants of the GFRDeterminants of the GFR (Fluid Dynamics)The GFR is determined by “Net filtration pressure”

Which is determined by the the following forces:


(3) Osmotic pressure of glomerular capillary - Opposes filtration

(4) Osmotic pressure in Bowman’s capsule - Promotes filtration

– We know that, protein is not filtered through glomerulus.

– Concentration of protein in the glomerular filtrate is so low that the colloid osmotic pressure of the Bowman’s capsule fluid is considered to be zero.

Determinants of the GFRDeterminants of the GFR (Fluid Dynamics)The GFR is determined by “Net filtration pressure”

Which is determined by the the following forces:


Calculation of GFRCalculation of GFR

Glomerular hydrostatic pressureGlomerular hydrostatic pressure

• It is determined by three variables:

(1) Arterial pressure∞ ∞ GFRGFR

(1) Afferent arteriolar resistance 1/∞ GFR1/∞ GFR

(3) Efferent arteriolar resistance

∞ ∞ GFR GFR in the beginning; later onin the beginning; later on 1/∞ GFR 1/∞ GFR

The initial increase causes blood to stay in glomerulus for longer The initial increase causes blood to stay in glomerulus for longer time thus GFR increases , but as soon as resistance increases time thus GFR increases , but as soon as resistance increases more than 3 folds in efferent arteriole the RPF decreases, So GFR more than 3 folds in efferent arteriole the RPF decreases, So GFR also declinesalso declines

Filtration Fraction Filtration Fraction ( FF = GFR / RPF )( FF = GFR / RPF )

• It is the ratio of the GFR to the RPF.

• Increasing the filtration fraction also concentrates the plasma proteins and raises the glomerular colloid osmotic pressure.

Control of GFRControl of GFR


• Norepinephrine & Epinephrine

– Released from the adrenal medulla.

– They constrict afferent and efferent arterioles, causing reductions in RBF & thus GFR is reduced.

• Endothelin Endothelin

– Released by damaged vascular endothelial cells

– It is a powerful vasoconstrictor.

– Causes renal vasoconstriction & thus decreases GFR .


• Endothelial-Derived Nitric OxideEndothelial-Derived Nitric Oxide

– Released by the endothelium.

– Decreases Renal Vascular Resistance and Increases GFR

• Prostaglandins and BradykininProstaglandins and Bradykinin

– It causes vasodilation & GFR is increased.

– These vasodilators are not of major importance in regulating GFR in normal conditions, but Under stressful conditions, such as volume depletion or after surgery, the administration of nonsteroidal anti-inflammatory drugs (NSAID’s), such as aspirin, that inhibit prostaglandin synthesis may cause significant reductions in GFR.


• Angiotensin IIAngiotensin II

– It preferentially constricts efferent arterioles.

– It should be kept in mind that increased angiotensin II formation usually occurs in circumstances associated with volume depletion, which tend to decrease GFR.

– In these circumstances, angiotensin II, by constricting efferent arterioles, helps prevent decreases in glomerular hydrostatic pressure and GFR.

– Thus it is better to say “Angiotensin II prevents ↓in GFR due to volume depletion”

Tubuloglomerular FeedbackTubuloglomerular Feedback

• This feedback autoregulates RBF and GFR.

• This mechanism is specifically directed toward stabilizing NaCl delivery to the distal tubule.

• Has two components:

(1) An afferent arteriolar feedback mechanism

(2) An efferent arteriolar feedback mechanism.

• These feedback mechanisms depend on special anatomical arrangements of the Juxtaglomerular apparatusJuxtaglomerular apparatus

Tubuloglomerular FeedbackTubuloglomerular FeedbackJuxtaglomerular apparatusJuxtaglomerular apparatus

(1) Macula densa (1) Macula densa

(2) Juxtaglomerular (JG) cells(2) Juxtaglomerular (JG) cells

(3) Extraglomerular mesangium(3) Extraglomerular mesangium

Tubuloglomerular FeedbackTubuloglomerular Feedback

• Not completely understood.

• Experiment suggests that decreased GFR slows the flow rate in the loop of Henle, causing increased reabsorption of sodium and chloride ions in the ascending loop of Henle, thereby reducing the concentration of sodium chloride at the macula densa cells.

Tubuloglomerular FeedbackTubuloglomerular Feedback• This decrease in sodium chloride concentration initiates a signal from the

macula densa that has two effects :

1. It decreases resistance to blood flow in the afferent arterioles

– Which raises glomerular hydrostatic pressure and helps return GFR toward normal

2. It increases renin release from the juxtaglomerular cells

– Renin increases the formation of angiotensin I from angiotensinogen, which is converted to angiotensin II.

– Finally, the angiotensin II constricts the efferent arterioles, thereby increasing glomerular hydrostatic pressure and returning GFR toward normal.

TubuloglomerularTubuloglomerular FeedbackFeedback

Myogenic Autoregulation of Renal Myogenic Autoregulation of Renal Blood Flow and GFRBlood Flow and GFR

• Another mechanism that contributes to maintenance of a relatively constant renal blood flow and GFR.

• Ability of individual blood vessels to resist stretching during increased arterial pressure, a phenomenon referred to as the myogenic mechanism.

• Muscles of small arterioles respond to increased wall tension or wall stretch by contraction of the vascular smooth muscle.

Myogenic Autoregulation of Renal Myogenic Autoregulation of Renal Blood Flow and GFR Blood Flow and GFR (cont.)(cont.)

• Stretch of the vascular wall allows increased movement of calcium ions from the extracellular fluid into the cells, causing them to contract.

• This contraction prevents over distention of the vessel and at the same time, by raising vascular resistance, helps prevent excessive increases in renal blood flow and GFR when arterial pressure increases.

Why increased protein intake causes Why increased protein intake causes increased GFR?increased GFR?

• GFR and renal blood flow increase 20 to 30 per cent within 1 or 2 hours after a person eats a high-protein meal.

Possible explanation is the following:

• Increased release of AA in blood, which are reabsorbed in the PCT.

• AA and sodium are reabsorbed together by the proximal tubules, increased amino acid reabsorption also stimulates sodium reabsorption in PCT.

• This decreases sodium delivery to the macula densa, which elicits a tubuloglomerular.

• Decreased afferent arteriolar resistance then raises renal blood flow and GFR.

Why polyuria in Diabetes?Why polyuria in Diabetes?

• Large increases in blood glucose levels in uncontrolled diabetes mellitus.

• Because glucose is also reabsorbed along with sodium in PCT, increased glucose delivery to the tubules causes them to reabsorb excess sodium along with glucose.

• This, in turn, decreases delivery of sodium chloride to the macula densa, activating a tubuloglomerular feedback.

DM , HTNDM , HTN

Urinary tract obstruction (kidney stone)Urinary tract obstruction (kidney stone)

↑↑ plasma proteinsplasma proteins

↓↓Arterial pressure in fluid loss Arterial pressure in fluid loss

↓↓Angiotensin IIAngiotensin II

↑↑Sympathetic activity, vasoconstrictorSympathetic activity, vasoconstrictorhormones (NE, Endothelin)hormones (NE, Endothelin)

To be continued…To be continued…

Renal physiology 2

Health & Medicine

Transcript of Renal physiology 2