1.1 Renal Physio Pt. 1&2 - Mariano

PHYSIO B 1.1 RENAL PHYSIOLOGY PT. 1&2 [DR. VILA] FEU-NRMF INSTITUTE OF MEDICINE 11.03.14 – 11.04.14

Physiologic Anatomy:

Kidneys o o o

o

Part of the urinary system Formation of urine Excretion of waste products, specifically water-soluble waste products A small portion of water-soluble waste products is excreted via the skin as sweat, but majority is excreted by the kidneys as urine

Function: Excretion of metabolic waste products o Regulate water and electrolyte balance o Regulate body fluid osmolality and blood o pressure *Body fluid: specifically extracellular fluid (ECF) ECF as: 1. Intravascular fluid – within blood vessels 2. Interstitial fluid  –  space bet. blood vessels and cells 3. Transcellular fluid  –  space other than intravascular and interstitium (ex.) CSF, perilymph, endolymph, peritoneal, pericardial, etc. *Vascular Physio Review* Increase fluid intake   increase BV  increase VR   increase EDV   increase SV   increase CO  increase BP

Renal hilum  –  where blood vessels, nerves and lymph enter, where ureter exits 2 layers: Outer cortex o Inner medulla (landmark: renal pyramids) o Apex (renal papilla) of renal pyramids drains into minor calyx  major calyx  renal pelvis  ureter Blood supply: Renal artery Segmental artery Interlobar artery Arcuate artery Interlobular artery

BP= CO x TPR CO= HR x SV SV= EDV – ESV

Afferent arteriole Glomerular capillay

o o

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Regulate arterial BP Regulate acid-base balance 3 systems maintaining acid-base o balance: Blood, respiratory and renal o Normal blood pH: 7.35  –  7.45 (slightly basic) Regulate gluconeogenesis

Peritubular capillary Vasa Recta (Cortical nephron) (Juxtamedullary nephron) *True capillary  – peritubular capillary

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Blood Supply:

Renal Blood Flow: About 22% of o (1100mL/min)

the

cardiac

output

Structural & Functional unit of the kidney: Nephron: 1 million per kidney o After 40 years old, there will be a o decrement of 10% per 10 years

Starling’s forces: 1. Capillary Hydrostatic Pressure 2. Capillary Osmotic Pressure Protein Pressure 3. Interstitium/tissue HP 4. Interstitium/ tissue OPPP o o

of

Plasma

Hydrostatic Pressure – drive away fluid Osmotic Pressure of Plasma Proteins  – attracts fluid (contributed largely by proteins)

Forces favoring filtration: o cHP & iOPP Forces favoring reabsorption: o cOPP & iHP Glomerular capillary: High pressure capillary bed o o 60mmHg Favors filtration o

Types of nephron: 1. Cortical – outer-cortex and mid-cortex Shorter loop of Henle o More numerous o Supplied by peritubular capillary o 2. Juxtamedullary o Longer and straighter loop of Henle o Supplied by vasa recta o Concentrates urine Nephron  –  from renal corpuscle (glomerulus + Bowman’s capsule) to distal tubule Urineferous tubule  –  connecting tubules and collecting tubuless Urge to urinate: 150mL (for a normal 70kg person) Urinary/micturition reflex: 700mL or 1L

Peritubular capillary / vasa recta Lower pressure o o 13mmHg Favors reabsorption o 2|Page

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Filtration barrier:

1. Basement membrane o Lamina densa: central dense layer o Lamina rara interna and externa  – proteoglycans which contribute to the membrane’s negative charge 2. Glomerular endothelium fenestrated, with fixed negative o charges that inhibit passage of plasma proteins 3. Layer of epithelial cells surrounding the glomerulus

(podocytes)

Glomerular capillary: o Fenestrated capillary without diaphragm o Size selective  –  does not allow large molecules to pass through o Shape selective  –  basal lamina is usually electronegative, therefore does not allow negative substances to pass through o Shape selective

Reabsorption

= cOPPP + iHP = 13mmHg + 37mmHg = 50mmHg

Filtration

= cHP + iOPPP =60mmHg + 0mmHg (zero pressure because no proteins were filtered) = 60mmHg

Net filtration pressure = Filtration – Reabsorption = 60mmHg – 50mmHg = +10mmHg (if positive value= filtration; negative value= reabsorption)

Intraglomerular mesangial cells: Contractile – in response to angiotensin o Phagocytic o

Net Glomerular Filtration Colloid osmotic pressure in Bowman’s space is absent or zero, supposedly , because protein is not filtered by the glomerulus. Remember, protein largely contributes to osmotic pressure. Since walang protein na-filter, walang osmotic pressure.

Colloid osmotic pressure is high in efferent arteriole and peritubular capillaries. Why? Since hindi na-filter si protein, pupunta siya ngayon sa efferent arteriole at peritubular capillaries, which then contributes to a higher osmotic pressure, favoring reabsorption. 3|Page

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JG Apparatus:

1. Macula densa: o Determine Na content in the filtrate Found near distal tubule o Columnar cells o 2. JG cells: Secrete renin o Modified tunica media of the o afferent arteriole 3. Lacis cells: Produce erythropoietin o Mainly serve as communication o between macula densa and JG cells  According to Doc Vila: **True location of macula densa : Thick ascending limb of Loop of Henle AND the beginning of the distal tubule.

** Most of the JG cells are located near afferent arteriole. However, some are also located near efferent arteriole.

Urine Formation:

Plasma   filtered by glomerulus   filtered substances move into Bowman’s capsule   pass through the tubules for reabsorption  secretion of of other substances from peritubular capillaries to tubules  excretion Therefore: Excretion = Filtration – Reabsorption + Secretion Waste Materials: Urea: from amino acids Creatinine: from muscle degradation Uric Acid: from nucleic acids Bilirubin: from hemoglobin Renal Clearance: The renal clearance (C) of a substance (s) is the volume of plasma required to supply the amount of substance excreted in the urine during a given period of time.

=

    

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o

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Principle of clearance: What is taken in should be equal to what is given out. Source of input for the kidney: Renal artery Output: May go into the urine or it may remain the plasma. Why? Not all substances are filtered so it goes to the efferent arterioles and peritubular capillaries or into the urine.

A. Substance is freely filtered by glomerular capillaries, neither reabsorbed nor secreted. Excretion rate = Filtration rate (Ex: Waste products like creatinine) B. Subtance is freely filtered, and partially reabsorbed. Excretion= Filtration – Reabsorption (Ex: electrolytes like Na and Cl) C. Substance is freely filtered and completely reabsorbed. Therefore, no substance is excreted. (Ex: Glucose and amino acids) D. Substance is freely filtered, not reabsorbed and partially secretion. (Ex: Organic acids and bases) Glomerular Filtration Rate (GFR)

 =  −    GFR = 125mL/min 7500mL/hour 180L/day  =  =

 

The gold standard for measuring the GFR is inulin, because it is freely filtered, and neither reabsorbed nor secreted. However, inulin is not produced by the body and has to be introduced to the subject via IV infusion. The routine substance used to determine GFR is creatinine, because it is naturally produced by the body. Creatinine is freely filtered, but it is partially secreted (20%). For a substance to be used as a measure for GFR: Must be freely filtered o Not reasbsorbed nor secreted o Not metabolized or synthesized by the body o (especially the kidneys) o Does not alter filtration rate

Filtration Fraction =

 

, where RPF = Renal Plasma Flow

Although, nearly all the plasma that enters the kidneys passes through the glomerulus, approximately 10% does not. The portion of filtered plasma is termed filtration fraction. 5|Page

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Factors affecting GFR:

BOTH afferent and efferent arterioles VASODILATE: More flow o o SAME GFR

Renal Blood Flow: 22% of the CO (1,100mL/min) o Based on Fick’s Principle:

=

∆

Q= blood flow P= arterial pressure R= resistance to flow o

o o

Flow = volume / time Velocity = distance / time

Vasodilation = Increase flow; decrese velocity o Increase diameter to accommodate more substance  increase flow Vasoconstriction = Decrese flow, increase velocity Decrease diameter to accommodate less o substance  decrease flow If afferent arterioles VASODILATE: More flow o More hydrostatic pressure o More GFR o If afferent arterioles VASOCONSTRICT: Less flow o Less hydrostatic pressure o Less GFR o If efferent arterioles VASODILATE: More flow o Less hydrostatic pressure o Less GFR o

o



Vasodilate: increase flow, decrease resistance Vasoconstrict: increase resistance, decrease flow

 =    −       Clearance can be used to estimate RBF. Substance used to measure RBF is para-aminohipuric acid (PAH). It is freely filtered, neither secreted nor reabsorbed and not metabolized by the body.   =  =  Effective Renal Plasma Flow =

   =

  

 

Extraction ratio is the difference between subsances in artery and vein over substamces in artery

If efferent arterioles VASOCONSTRICT: Less flow o More hydrostatic pressure o More GFR o

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Autoregulation: Inherent mechanism of kidney in o maintaining RBF and GFR at a relatively constant level over an arterial pressure range between 80 – 170mmHg Also influenced by nervous mechanism, o hormones, autocoids and others. *CVS Review: Mean Arterial Pressure= Diastolic Pressure – 1/3 Pulse Pressure = 80- 170mmHg Mechanisms: 1. Myogenic mechanism Pressure-sensitive o Tendency of vascular smooth muscle to o contract when pressure increases When arterial pressure increases, and o afferent arterioles is stretched, smooth mucscle contract

o

The increase in resistance of the arteriole offsets the increase in pressure, therfore making the RBF and GFR constant, provided that P and R remain constant. Based on Fick’s Principle: ∆ = 

2. Glomerulotubular Feedback The greater amount of substance being o filtered will have a concomittant amount of substance being reabsorbed to maintain homeostasis o Constant proportion of substances 3. Tubuloglomerular Feedback o JG apparatus When GFR increases and Na concentration o also increases, which is detected by the macula densa

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o

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This will lead the macula densa to degrade ATP to adenosine Adenosine  will cause vasoconstriction of the AFFERENT arteriole due to the presence Adenosine 1 receptors Vasoconstriction will then decrease the GFR back to normal When GFR decreases, there is low Na concentration, which is detected by the macula densa Macula densa will then cause the JG cells to secrete renin Renin will then activate angiotensinogen to angiotensin I Angiotensin I will then be converted to angiotensin II by ACE in the lungs will then cause Angiotensin II   vasoconstriction of the EFFERENT arteriole, causing an increase of GFR back to normal

Nerve Innervation Sympathetic NS o o Act via beta receptors present in JG cells JG cells secrete renin o Renin will cause Na reabsorption o particularly in the proximal tubules Increase Na   Increase fluid intake  o increase BV  increase VR  increase EDV   increase SV   increase CO   increase BP Obligatory reabsorption   is seen in the proximal tubules due to the presence of brush borders.

Tubular Reabsorption

4. Nervous mechanism Exclusively Sympathetic NS o Strong activation of renal sympa: o o Vasoconstrict renal arterioles Decrease RBF and GFR o Moderate or mild activation: o Little influence on RBF and GFR o 5. Hormones and autocoids o Norepinephrine o Epinephrine  (80% produced by adrenal medulla) o Endothelin Most potent vasoconstrictor o Released from damaged endothelial o cells of the kidneys NE and Epi can constrict the afferent and o efferent arterioles but only if they are in high amounts o Angiotensin II Vasoconstrict EFFERENT arteriole o o Endothelin-derived Nitric Oxide Vasodilate o o Increase GFR but eventually becomes stable o Prostaglandin and Bradykinin Vasodilate o Increase GFR, but eventually o becomes stable

2 reabsorption pathways: o Transcellular: Luminal and membrane o Paracellular: via tight junctions

basolateral

Transport Limitation o

TM Limited (Transport Maxima) Glucose, SO4, PO4, amino acids, o lactate, malate and Vitamin C Active transport o Exhibits saturation o When saturated, rate of transport o remains constant

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Gradient-time Limited Na, Cl and HCO3 o o Mostly passive, but can also be active transport The greater the concentration o gradient, more substances are transported The longer the time, more o substances are transported

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