PATH OF BLOOD

-          Renal artery

-          Interlobar artery

-          Arcuate artery

-          Cortical radial artery

-          Afferent arteriole

-          Glomerular capillary network

-          Efferent arteriole

-          Peritubular capillary network

-          Renal Vein

NEPHRON

Renal corpuscle

            Glomerulus- located in cortex

                        Filtration Barrier

Endothelial cells (fenestrated)

Basement Membrane

Podocytes (epithelial cells of viseral layer of Bowman’s capsule)

Foot processes

                                                Slit pore (diaphragm)

Bowman’s space

            Bowman’s capsule

Proximal tubule

            Convoluted and straight

Brush border

            Numerous mitochondria

Loop of Henle

            Thin desending

                        Few mitochondria

                        High permeability to water

            Thin ascending

                        Few mitochondria

                        Low permeability to water

                        High permeability to Na⁺ and urea

            Thick ascending

                        Numerous mitochondria

                        Low permeability to water

Distal Convoluted Tubule

                        Thick

                        Numerous mitochondria

                        ADH effect

Collecting duct

            Thick

            ADH effect

            Cortical

            Outer medullary

            Inner medullary

Juxtaglomerular Apparatus (JGA)

Location:

            Vascular pole of glomerulus (where afferent and efferent arteriole enter glomerulus)

Components:

Macula densa cells (modified early distal tubule cells)

Lacis (extraglomerular mesangium celss

Granular endothelial cells (renin)

Vasa Recta – countercurrent exchange system

Function:

            Solute removal

            Water removal

Two types of Nephrons

1.       Cortical (superficial)

Renal corpuscle in outer cortex

Lower filtration rate

Short loops of Henle

Peritubular capillary network

No vasa recta

2.       Juxtamedullary

Renal corpuscle in deep cortex

Higher filtration rate

Long loops of Henle

Peritubular capillary network

Vasa recta

180 L/day glomerular filtrate

BODY FLUIDS

Total body water = 60%

            Extracellular = 20% (1/3 TBW)

                        16% interstitial

                         4% plasma

Intracellular = 40% (2/3 TBW)

Cell membrane is permeable to water but not to most solutes.

Measurements

Dye dilution technique (in compartment in which it distributes)

Total body water ® Radioactive water

Extracellular water ® Inulin or radioactive sodium

Plasma ® Tagged albumin

Volume = amount injected/ concentration in sample

Intracellular = Total – ECF                  Interstitial = ECF - plasma

ESTIMATING BODY FLUID CONCENTRATION

Plasma concentration (mOsm/L) = (2 x Plasma Na⁺) + (plasma glucose/18) + (plasma BUN/2.8)

Posm (plasma osmolality) = 2 (Na⁺_E + K⁺_I) / TBW

STARLING’S EQUILIBRIUM

Q = K_f (P_c – P_i) - s (p_c - p_i)

P_c ® favors filtration

P_i ® does not favor filtration

p_c ® does not favor filtration

p_i ® favors filtration

Hydration

­ ECF volume, ¯ [ECF], water moves ECF ® ICF, ­ ICF volume, ¯ [ICF]

Dehydration

¯ ECF volume, ­ [ECF], water moves ICF ® ECF, ¯ ICF volume, ­ [ICF]

Hemorrhage

¯ ECF volume, [ECF] stays the same

Isotonic saline

­ ECF volume, [ECF] stays the same

Hypertonic  saline (increase NaCl)

­ ECF volume, ­ [ECF], water moves ICF ® ECF, ¯ ICF volume, ­ [ICF], ­ ECF volume

Loss of NaCl

¯ [ECF], water moves ECF ® ICF, ­ ICF volume, ¯ [ICF] 

Filtration equilibrium = no net filtration/absorption ( P_c - p_c - P_i = 0 )

Freely filtered: concentration in the afferent and efferent arterioles are the same

Glucose            Chlorine

Inulin                Potassium

Sodium             Creatine

­ molecular size : permeability ¯

For a given molecular size permeability: (+) > neutral > (-) (only the smallest anions can be filtered)

Donnan effect: impermeable negatively charged proteins effect the electrochemical equilibrium

How can one increase GFR while ¯ renal blood flow?  Constrict the efferent arteriole.

Glomerulotubular feedback ® matching of proximal tubule reabsorption to filtering of glomerulus

Characteristics of a substance used to calculate GFR

1.       freely filtered       

2.      not reabsorbed                               GFR = [inulin]_urine x V_u

3.       not secreted                                                               [inulin]_plasma

CLEARANCE = the volume of plasma equal to that which originally contained the amount of a given

 solute which is excreted in one minute’s time

If not reabsorbed or secreted            clearance = GFR

If secreted                                clearance > GFR

If absorbed                               clearance < GFR

Clearance = [X]_u x V_u                                             

                        [X]_p

As [X]_p ­, clearance approaches GFR (the clearance of inulin/creatine)

TP/P RATIO = [where you are] / [plasma]

Bowman’s space

= 1 for freely filtered small uncharged molecules, < 1 for larger molecules

In any given tubule

Ratio is > inulin ratio then solute is secreted

Ratio is < inulin ratio then solute is absorbed

Distrubution of Renal Blood flow

Cortex              ~ 100%

Outer medulla            < 10%

Inner medulla       2-3%

T_m = transport maximum

The constant amount of a compound that will be secreted / reasorbed by the renal tubules per minute

When is the max clearance for any compound?  When the compound is being secreted at T_m.

Renal Threshold

[plasma] when the compound first appears in the urine

Splay

Instead of reaching T_m and excreting glucose suddenly, reabsorption capability falls off gradually and excretion begins gradually due to the kidney “missing one” here and there near transport maxium.

ALDOSTERONE

1.       ­ apical permeability to Na⁺

2.       ­ energy for active pump on basolateral

3.       ­ rate of pump

4.       Basolateral surface of principal cell increases on apical membrane

5.       Amiloride can block aldosterone effect

Aldosterone escape ® excretion = intake eventually

-          when aldosterone is given at first Na⁺ excretion ¯

-          then aldosterone excretion = intake (but weight is ­ due to water retention)

-          when aldosterone is stopped at first Na⁺ excretion ­

-          then aldosterone excretion = intake (weight goes back to normal)

G-T Balance

1.       Constriction of efferent arteriole causes drop in capillary hydrostatic pressure (P_c) to increase net reabsorption

2.       Interstitial oncotic pressure (p_i) increases due to ­ glucose reabsorbed and water follows.

Renin – Angiotensin – Aldosterone System

Renin release from JGA

              Baroreception in afferent arterioles (detect ¯ pressure)

              ¯ NaCl flowing at the macula densa

              sympathetic nerve influence

renin splits angiotensinogen (liver) ® angiotensin I

ACE (lungs) converts angiotensin I ® angiotensin II ®adrenal cortex secrete aldosterone

angiotensin II

              retention of Na⁺ in proximal tubules, and indirectly distally via aldosterone

             (­ECF, ­CO)

              vasocontrictor action (­TPR)

              stimulating thirst and release of ADH