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1 1 BIOL. 2402 Anatomy & Physiology WEEK 12 Urinary System Collin County Community College 2 Glomerular Filtration • Filtration process that occurs in Bowman’s Capsule Blood is filtered and the filtrate ends up in the tubule system of the nephron What creates the filter system ? Combination of the membrane systems of the capillaries and Bowman’s capsule cells RENAL PHYSIOLOGY

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Page 1: BIOL. 2402 Anatomy & Physiologyfaculty.collin.edu/cdoumen/2402/2402/5_Urinary/2402Kidney2ppt.pdf · Net filtration pressure is determined by the 3 forces Filtration System in Bowman’s

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BIOL. 2402Anatomy & Physiology

WEEK 12

Urinary System

Collin County Community College

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Glomerular Filtration

• Filtration process that occurs in Bowman’s Capsule

• Blood is filtered and the filtrate ends up in the tubulesystem of the nephron

What creates the filter system ?

Combination of the membrane systems of thecapillaries and Bowman’s capsule cells

RENAL PHYSIOLOGY

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Microscopic Anatomy of Bowman’s Capsule

Special cells, called Podocytes, cover the capillaries

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Podocyte in Bowman’s capsule

Microscopic Anatomy of Bowman’s Capsule

Pedicels of podocytes (feet extensions) create filtration slits

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Microscopic Anatomy of Bowman’s Capsule

Scanning electron microscope picture of thefingerlike filtration slits of the podocytes !

Compare this with the diagram on left sideand previous slide !

This system provides a filteringmechanism roughly similar to acoffee filter, but much more refined !

It houses 3 filtering mechanisms !

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Capillary endothelial cellshave many pores

• let everything through exceptblood cells and large proteins

Basement membrane orBasal Lamina

• Is negatively charged andrepels most smaller proteins

Foot process of thePodocytes

• Form additional filtration slitsthat only let small moleculesthrough

Filtration System in Bowman’s capsule

Microscopic Anatomy of Bowman’s Capsule

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What are the forces involved the filter system ?

• Similar forces that are involved in capillary fluidexchange in the tissues !

• Hydrostatic pressure from the blood ( = bloodpressure )

• Hydrostatic pressure in capsule from the filtrate

• Osmotic (oncotic) pressure from the blood

Filtration System in Bowman’s capsule

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Filtration System in Bowman’s capsule

• Filtration occurs as fluids move across the glomerulus• The positive filtration pressure is the glomerular hydrostatic

pressure due to blood pressure in the glomerular capillaries(GHP)– Capsular hydrostatic pressure opposes (CsHP)– Blood colloid osmotic pressure opposes (BCOP)

• Net hydrostatic pressure (NHP) = GHP – CsHP

Net Filtration Pressure (NFP) = GHP - CsHP - BCOP = NHP – BCOP

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Net filtration pressure is thus a modest 10 mm Hg

Net filtration pressure is determined by the 3 forces

Filtration System in Bowman’s capsule

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Net Filtration pressure (NFP)

• Pressure force that drives fluid out of the blood(out of the glomerulus) and into Bowman’scapsule

• Due to the characteristics of the ‘filter’, the filtratethat passes into the tubule system of the nephronequals blood minus formed elements and minusproteins

• Since proteins do not leave the blood stream, butwater does, the efferent arteriole will have a higherconcentration of proteins and blood cells ( will bemore viscous) !

Bowman’s capsule

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Glomerular Filtration Rate (GFR)

Total amount of filtrate formed per minute by the kidneys.

Depends on :• NFP

• what happens when NFP = 0 ?• what happens to NFP when BP increases ?• what happens when afferent blood osmolarity

increases ? ( use next slide )• Total filtration area ( what happens with a unilateral

nephrectomy ? )

• Filtration membrane permeability ( what happenswhen some Glomeruli get clogged up ? )

Bowman’s capsule

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Blood pressure changesaffect this force

Blood proteins changesaffect this force

Bowman’s capsule

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Regulation of GFR

Regulation of the GFR is an important homeostatic process.

• If GFR is too high, we would produce a high rate of filtrateand re-absorption of essential elements would not beefficient.

• If GFR is too low, we would not be able to secreteimportant waste products fast enough

Regulation of the GFR occurs via 3 mechanisms

• Renal Auto-regulation• Neural regulation• Renin-Angiotensin Feedback

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1. Renal Auto-regulation

a. Juxta Glomerular Apparatus (JGA) feedback

• Distal Convoluted tubule makes contact with afferentand efferent arteriole

• This region is called the JGA

• Contains 2 groups of cells that are important inkidney function

• Juxta glomerular cells : are part of the afferentarteriole wall and act as mechano-receptors andendocrine cells

• Macula Densa cells : are part of the DCT andthey act as chemoreceptors/endocrine cells.

Regulation of GFR

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Regulation of GFR

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b. Myogenic Effect

• When blood vessels and smooth muscles are stretchedthey tend to contract

• Increased blood pressure will cause vasoconstriction inthe afferent arteriole and counteract a possible increasein NFP.

Regulation of GFR

1. Renal Auto-regulation

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Regulation of GFR

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2. Neural Regulation

• Mostly a sympathetic effect• Produces powerful vasoconstriction of afferent arteriole

• Decreases GFR and slows production of filtrate• Important for example during blood-loss ; prevents body

from excreting more urine ( fluid)

• Changes the regional pattern of blood flow• Alters GFR

• Also Stimulates release of renin by JGA

Regulation of GFR

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Regulation of GFR

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3. Renin-Angiotensin Feedback

The following will result in a Renin release by theJuxtaglomerular cells in JGA apparatus

• Drop in Blood pressure (reduced stretch in afferent arteriole)• Reduced release of the vasoconstrictor from the Macula Densa

cells ( thus, reduced Na+ flow in the DCT)• Direct stimulation of JG cells by sympathetic stimuli

• All these stimuli release Renin, resulting in Ang II production• Efferent arterioles have more Ang II receptors than Afferent

arterioles ; thus this will increase the Pressure in theglomerulus (why ? )

• Ang. II also results in release of Aldosterone and ADH( what do they do ? )

Regulation of GFR

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Regulation of GFR

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Regulation of GFR

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Regulation of GFR

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• Glomerular filtration produces fluid similar toplasma without proteins

• GFR ~ 125 ml per min

• If nothing else would happen, we would createurine at this rate.

• The result would be extreme water loss, and lossof all electrolytes and nutrients.

Summary of Glomerular Filtrate

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The function of the nephron tubules is to reclaim asmuch possible of the essential elements and re-direct it back into the blood stream. This willinvolve :– Reabsorption important organic nutrients– Active and passive reabsorption of sodium and other

ions– Reabsorption of water

At the same time, unwanted chemical are added tothe filtrate via secretion from the blood streaminto the tubules.

Nephron tubule Function

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Nephron tubule Function

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Proximal Convoluted Tubule

The function of the PCT is :

– Reabsorption of most organic nutrients– Active reabsorption of sodium and other ions– Reabsorption of water

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Proximal Convoluted Tubule

Of the 125 ml of filtrate that enters the PCT perminute, only 40 ml/min passes on to the loop ofHenle

In addition, 60% of Na+ , 50% of K+ and Cl-, and100% of all organic nutrients and bicarbonate arereabsorbed !

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Proximal Convoluted Tubule

How does this occur ?

Re-absorption is due to an a-symmetrical arrangement andorganization of the epithelial cells lining the proximaltubule

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Proximal Convoluted Tubule

Longitudinal section

Cross section

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Proximal Convoluted Tubule

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Proximal Convoluted Tubule

• The plasma membrane of each epithelial cell that does not facethe lumen– is called the baso-lateral membrane and resembles membranes of normal

cells– that area of these cell contains many Na-K pumps.– also contains many channels that promote facilitated diffusion for glucose

and amino acids

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Proximal Convoluted Tubule

• That part of the epithelial cell facing the lumen of the proximaltubule– has a plasma membrane forming many microvilli (brush border)– the apical part of each epithelium cell ( thus the part which forms the brush

border) does not contain Na-K pumps but does contain Na+ leakagechannels and Cl- leakage channels

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Proximal Convoluted Tubule

• The Na-K pumps in the baso-lateral membrane function as usual:pumps Na out and K in, keeping Na low inside the cell by usingATP.

• This creates a high gradient for Na from lumen of the PCT intothe cell of the PCT. Sodium will then diffuse into the cell viaspecific Na-leakage channels located in the brushborder ( andsodium will leave again via the basolateral membrane via Na-Kpumps)

• To maintain electrical neutrality, each Na moved in will promotethe movement of a negative charge ( Chloride ion) via leakagechannels for that ion

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Proximal Convoluted Tubule

Na+

K+

Na+

PCT cellLumen Interstitialfluid

• Active transport of sodium out of the cell at the basolateralmembrane thus promotes the re-absorption of sodium at thebrush border area .

• The re-absorption of Sodium and Chloride promotes the uptakeof water in order to maintain osmotic equilibrium

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• As blood flows from the glomerulus to the peritubularcapillaries, it has a higher osmotic concentration.

• There is also a substantial drop in pressure.

• The pressure forces are now revered.• Hydrostratic pressure of the blood ~ (15 mm Hg ; an

outward force)• Blood osmotic pressure ~ (30 mm Hg ; inward force)• Interstitial pressure ~ ( 2 mm Hg ; inward)

• Net Force = 15 - 2 - 30 = -17 mm Hg into the peritubularcapillaries.

Forces at the Peritubular Capillaries

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Proximal Convoluted Tubule

Na+

K+

Na+

PCT cellLumen Interstitialfluid

-17 mm HgDriving pressure

PTC

H2O

This force helps to drive the Na+ and waterback into the blood stream

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• Brush border membranes also contain channels that couplethe movement of sodium to that of glucose (secondary activetransport- cotransport)

• Similar transport systems are present for amino acids to thatof certain amino

• Thus movement of sodium down its concentration gradientdrags glucose in, even when glucose is higher in the cell

• Results in a build up of glucose in the cell which then leavesthe cell via facilitated diffusion channels in the basolateralmembrane to be reabsorbed by the peritubular capillaries

Glucose re-absorption in PCT

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Proximal Convoluted Tubule

Na+

K+Na+

PCT cellLumen Interstitialfluid

-17 mm HgDriving pressure

PTC

GlucGluc

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Proximal Convoluted Tubule

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Proximal Convoluted Tubule

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Proximal Convoluted Tubule

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Normally all amino acids and glucose are reabsorbed by theproximal tubule.

However, when the transporters are 'over-loaded" because theirmaximal transport capacity is surpassed, these componentsstart to spill over into the urine

Maximal transport rate of the transporters is called the Tmvalue .

Proximal Convoluted Tubule

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Renal Threshold = plasma concentration at which a substancestart to spill over into the urine

When this happens,urine volume increasesas well.This because for eachion or molecule that isnot reabsorbed, lesswater is redirected viaosmosis (and thus endsup in the urine).

Proximal Convoluted Tubule

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Proximal Convoluted Tubule

Under normal conditions, renal Threshold is rarely reached.The exceptional cases are for example hyperglycemia as seenin diabetes mellitus.

Renal glycosuria :Defective carriers that

don’t allow the PCTto reabsorb glucose.