1. Renal Functions & Glomerular Filtration

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 Kidney Functions...... 3  Nephron Structure...... 4  Renal Blood Vessels...... 7  Renal Blood Flow...... 8  Urine Formation...... 9  Glomerular Membrane...... 11  Glomerular Filtration Rate ...... 13  Starling’s Forces ...... 14  Changes in Forces ...... 15  Afferent & Efferent Arteriolar Resistance Affect...16  Factors Affecting Renal Blood Flow & GFR...... 18  Composition of Glomerular Filtration...... 20  Innervation of the kidney...... 20  Summary...... 21  Questions...... 23

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 Filter 200 liters of blood daily, from toxins, metabolic wastes  Regulation of :  Water and electrolyte balance.  Arterial blood pressure.  Body fluid osmolality & electrolytes.  Acid/base balance  Excretion of :  Waste products : Urea Creatinine Uric Acid  Bioactive substances such as hormones and many foreign substances, especially drugs.  Synthetic Functions :  Active form of vit D = 1,25 dihydroxychlicalciferol  Erythropoietin production  Renin formation 3  Synthesis of glucose from amino acids during prolonged fasting

What is The Functional & structural Unit of The Kidney? The Nephron  Each kidney has 1 million nephrons, each nephron is capable of urine formation.

 Structure of a Nephron

o The Glomerulus: which is the capillary tuft: in which large amount of fluid is filtered from blood.

o Bwaman’s capsule: Around the glomerulus and receives the filtrate.

o Tubules: in which filtered fluid eventually is converted into urine. 4  Renal Tubules Proximal convoluted tubule (in cortex) composed of 1- microvilli 2-cobodial cells and mitocndia Function : Reabsorbs water and solutes from filtrate and secretes substances into it

Loop of Henle smellier to Proximal convoluted tubule

Distal convoluted tubule (in renal cortex) composed of cuboidal cells without microvilli Function : more in secretion than reabsorption

 Types of Nephrons Cortical nephrons (85%) Located in the cortex – Short loop of Henle. Juxtamedullary nephrons: (15%) Located in the cortex-medulla junction Long loops of Henle that deeply invade the medulla. 5 Maintain salt gradient, help conserve water. Cortical

Loop on Henle

Renal Blood Vessels 2 3 2

1 Lecture 1 Afferent Deliveries blood into Arteriole glomeruli

AS IN ARRIVING

2 Glomerular Produces filtrate that Capillaries enters the tubules

Deliveries blood from 3 Efferent glomeruli to peritubular Arteriole capillaries

4 Mentioned in Males’ Slides of AS IN EXITING 7 4 Peritubular Vasa recta Which are long, hairpin-shaped blood vessels Capillaries

Renal Blood Flow 2 Renal blood flow to the kidney represents 20% of cardiac output

The blood flow to each kidney through a renal artery Lecture

 Features of Renal Circulation  High blood flow (1200 ml/min) Such high rate of RBF are not surprising in light of the central role the kidneys play in maintaining the volume and composition of fluids! 20%  Presence of 2 capillary beds: Glomerular & Peritubular.

 Efferent and afferent arterioles are Mentioned in Males’ Slides of major sites of resistance Due to the high pressure in those 2 arterioles. 8

Urine Formation 2 Primary function of the kidney is to ‘clear’ unneeded substances

from the blood to be excreted in urine Lecture Steps of Urine Formation (Renal Processes) 1. Filtration 1 Glomerular Filtration

2 Tubular Reabsorption 22 . Reabsorption

3 Tubular Secretion

3. Secretion Mentioned in Males’ Slides of 4 Excretion 44 . Excretion 9

Urinary Excretion Rate = Filtration Rate – Reabsorption + Secretion cont. Urine Formation 1 Glomerular Filtration 2 Tubular Reabsorption 3 Tubular Secretion 4 Urine Excretion 2  Movement of substances from  The first step in urine tubular lumen back into the blood formation “The end product”

 Reabsorbed substances not lost in The selective transfer of Lecture  Blood flows through the the urine, but are carried by the substances from the The elimination of glomerulus, allowing peritubular capillaries to the venous peritubular capillary into substances from the protein-free plasma to be system the tubular lumen body in the urine filtered through the

glomerular capillaries into  Most of the filtered plasma is the Bowman’s capsule. reabsorbed Types o Transcellular (across the cell) o Paracellular (between cells) Allows for rapid o Active substances that are All plasma constituents elimination of substances

needed by the body (via primary filtered or secreted, but of Slides Males’ in from the plasma via  20% of plasma entering active transport based on ATP not reabsorbed remain extraction of the 80% of the glomerulus is filtered hydrolysis (e.g. Na+) or secondary in the tubules and pass unfiltered plasma in active transport based on an ion into the renal pelvis to

peritubular capillaries and Only  125 ml/min filtered fluid gradient (e.g. glucose) be excreted as urine adding it to the o Passive Bulk flow results from the and eliminated from substances already in the body imbalance of osmotic or hydrostatic tubule as result of filtration 10 forces at the peritubular capillary. Exactly the same as at the peripheral capillary or the glomerulus Glomerular Membrane It’s where the first step in renal processing occur which involves the filtration of plasma in the glomerulus

Composed of three layers : 1- Endothelium of the glomerular capillaries : it is fenestrated and the pores are about 50 – 100 nm in diameter. . 2- Basement membrane : composed of fused basal laminae of the other layers. . 3- Epithelial membrane : visceral membrane of glomerular capsule ( podocytes ).

Filtration Membrane : Filter that lies between the blood and the interior of the glomerular capsule. 11 Glomerular Membrane cont. - Glomerular filtration membrane is highly permeable to water and small molecules (less than 10.000 MW).

- Large molecules (more than 70.000 MW especially proteins are not filtered due to: 1- Their large size. 2- Negative electrical charge, because their passage is repulsed by negatively charged glycoproteins present on endothelial pores, basement membrane and podocytes. ( they will be repelled by negative charge in the membrane )

12 * Renal Plasma Flow Plasma *Renal glomerular glomerular GFR is determined by: 1 Pressure across the

: Starling’s Starling’s Forces The NFP = T he of rate production of filtrate atthe glomeruli from plasma per minute Net FiltrationNet capillaries Glomerular Filtration Rate

99 = GFR %

of of filtrate

GFR = = 125 10 NORMAL GFR WILL BE :

reabsorbed x x ml NFP NORMAL VALUES 12.5 / min 1

x K = 180 ,

f 2 to L/Day

2 L urine urine

excreted Surface Area (GFR)

2 capillary capillary filtration : K The glomerular

coefficient f =

= 20 12.5 % Permeability of of RPF

Mentioned in Males’ Slides of Lecture 2

Forces Controlling GFR Opposes Filtration 2 Starling’s Forces Promotes Filtration

The Net Filtration Pressure (NFP) is the sum of Lecture Pc Glomerular Hydrostatic Pressure = 60 mmHg

Colloid Osmotic Pressure of Glomerular plasma proteins NFP ✖ = 32 mmHg b = 0 Pb Bowman’s Hydrostatic Pressure = 18 mmHg As we knew that filtration membrane doesn't allow proteins to pass therefore Colloid Osmotic Pressure of bowman's space has NO Bowman’s proteins proteins which means = 0 mmHg oncotic pressure = 0 Mentioned in Males’ Slides of 14 NFP = (P -P ) - ( - ) C b c b Recall! NFP = ( 60 – 18 ) – (32 – 0) = 10 mmHg GFR = NFP x Kf = 10 x 12.5 = 125 ml/min

Changes in Forces & Affection of GFR 2

Increased Pc Increases GFR. This pressure is affected by:

ABP, Afferent & Efferent arteriolar resistance’ Lecture ‘: Constriction or dilation

Increased c Decreases GFR in which plasma proteins are Mentioned in Males’ Slides of increased. Increased Pb Decreases GFR 15 In urinary obstruction

e.g. stones or tumors. Pc = Glomerular hydrostatic pressure Pb = Bowman’s hydrostatic pressure = Colloid osmotic pressure of glomerular plasma proteins

Afferent & Efferent Arteriolar Resistance Affect 2 As vasodilation and vasoconstriction of the afferent and efferent arterioles alter the blood flow through the glomerular capillaries, there are corresponding alterations in the glomerular

filtration rate (GFR). Lecture

Constriction of Constriction of Efferent Afferent E.g.: Angiotensin II E.g.: Sympathetic o PGC o PGC o GFR o GFR

Dilation of Dilation of Efferent Afferent

o PGC o PGC Mentioned in Males’ Slides of o GFR o GFR 16

PGC = Glomerular Hydrostatic Pressure

Cont. To sum up the previous discussion on the changes which occur to RBF and GFR under different parameters..

Parameter RPF Pc c GFR

Afferent Constriction   NC 

Note: if severe Afferent Dilation   NC  vasoconstriction occur to the Moderate efferent the blood Efferent Constriction   NC  moves so slowly where GFR Severe increases and the Efferent Constriction  -   blood is almost completely filtered Efferent Dilation   NC  and the remaining plasma proteins will increase the Total Plasma Proteins NC NC   Additional oncotic pressure therefore GFR 17 decreases Total Plasma Proteins NC NC  

RBF = Renal Blood Flow PC = Glomerular Hydrostatic Pressure c = Glomerular Oncotic Pressure NC = No Change

Factors Affecting Renal Blood Flow & GFR 2

Factor GFR RBF Explanation Lecture

It causes constriction of kidney’s blood vessels. Sympathetic Stimulation of Moderate or mild sympathetic stimulation has little   influence on renal blood flow and GFR. While severe Renal Arterioles stimulation - in case of severe hemorrhage, brain ischemia - influences GFR a lot that it can lead to ARF

Norepinephrine   Released during sympathetic stimulation

Angiotensin II Angiotensin II is released in special conditions such as (Constricts efferent arteriole more than   reduced renal perfusion pressure due to renal artery

afferent) stenosis, to protect the kidney Mentioned in Males’ Slides of

After age 40, GFR decreases progressively with age, by Aging   about 0.4 - 1.2 mL/min per year. The exact mechanism 18 is yet unclear.

Factors Affecting Renal Blood Flow & GFR cont. 2

Factor GFR RBF Explanation Lecture 1- High-protein meal increases the release of amino acids into the blood. 2- Amino acids are reabsorbed in the proximal tubule with sodium. 3- Increased amino acid reabsorption also stimulates sodium reabsorption. 4- This decreases sodium delivery to the macula densa —> its feedback causes decrease in resistance of the afferent High Protein Diet   arterioles —> raises renal blood flow and GFR. 5- This increased GFR allows sodium excretion to be maintained at a nearly normal level while increasing the excretion of the waste products of protein metabolism, such as urea

This mechanism will be more clear if we take the tubular

reabsorption lecture  Mentioned in Males’ Slides of Hyperglycemia   (e.x: Diabetes mellitus) same cause as high protein diet 19 Fever   - Composition of Innervation of Glomerular Filtration : the kidney Glomerular Filtration has almost the Sympathetic nerves same composition as that of plasma, - supply renal blood vessels. except that it has no significant amount - regulate blood flow. of proteins (it has about 0.003%). - Filtration. - water reabsorption. Components are: - rennin secretion. • Water. It is less than • Electrolytes. 1/2000 protein

• Glucose. as compared Males’ in Slides

• Urea. with plasma.

• Creatinine.

“There is no parasympathetic Only

innervation”. 20 electrolyte Water and Acidity ABP component

Function

1 - Regulation

Cuboidal Cuboidal cells Reabsorbtion

Secretion Secretion microvilli Kidney Functions GFR = NFPx Waste PCT 2

Renal Renal tubule Excretion

NFP = (P

Cuboidal Cuboidal cells Loop Loop of Drugs Reabsorbtion Secretion Secretion microvilli

K C f

- 3 Henle P - Synthesitic b

)

( Cuboidal Cuboidal cells c

- Secretion

DCT b ) Erythropoietin

Vit D Vit Renin

Summary Filter that lies between the blood and the interior of the glomerular capsule Filtration Membrane

Endothelium Basement Epithelial

Membrane Membrane

Permeable to small molecule (less than 10.000 MW) *large molecule & negative charge molecule doesn't go throw ______It has the same molecule as the plasma except it no

significant amount of Summary proteins 22 C. Microvilli Microvilli C. B. A.Podocyte 2 A D. Cuboidal C. B. Microvilli A. distal convoluted : tubule 1 LoopC. Proximal B. DistalA. secretion reabsorption than : 3 D. D. A D. - - -

J Podocyte Which is released Renin by Which Juxtamedullary uxtaglomerular uxtaglomerular &C & C &

of convuluted one of following the tubules ismore in one of following the is acomposition of

Henle convuluted

cells

apparatus nephron

tubule tubule

1 : 9 2 1 8 3 2 1 7 Cortex 6 1 5 1 4 ------

Give Mention Mention water water electrical Negativecharge size. large Their Epithelial membrane Basement Microvilli renin Mention Juxtamedullary Proximal Endothelium Endothelium - 2 junction medulla reason proteins why 2 - 2 the 2

3 erythropoietin. erythropoietin. - convoluted tubule composed of

components secreted from thekidney: 2 glucose glucose membrane membrane components filters inglomerular filtration -

3 cuboidal cuboidal cells of layers in filtration membrane layers in :

glumerular nephron located in : 3

urea

do not capillary capillary

filtrated :

1 3 2 23 .C .A .B

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Done By:  Hussain alkaff  Ahmad Alzahrani  Abdullah Alfaleh  Maha Alrabiah  Reem Labani  Hadeel Alsulami 24  Nouf Almasoud