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					Chapter 4
Renal Function 

Dr Atef A Masad




Dr Atef Masad     Renal Function   1
         What do the kidneys do?
• Urine formation
• Regulate body fluid osmolality and volume
• Regulate electrolyte balance
• Regulate acid-base balance
• Excrete waste products and foreign
  substances
• Produce and excrete hormones such as
     Erythropoietin and Rennin


Dr Atef Masad          Renal Function     2
•The kidneys are a pair of fist-sized organs that 
are located on either side of the spinal column 
just behind the lower abdomen (L1-3). 
•The kidney is a component of the urinary tract 
system, which consists of kidneys, ureters, 
urinary bladder, and urethra. 
The urinary tract functions as a pathway for the 
elimination of metabolic by-products and 
unessential chemicals and removal of
potentially toxic waste products.




Dr Atef Masad         Renal Function                 3
                       Renal anatomy


                                            Cortex



            Pelvis                             Capsule


                                             Medulla



          To the bladder
Dr Atef Masad              Renal Function                4
•The kidney maintains the water, ionic, and 
chemical balance of blood by filtering chemicals 
from the blood and conserving, or reabsorbing, 
those chemicals that are needed for adequate 
metabolism. 
•The kidneys maintain the balance of plasma 
constituents, while excreting those substances that 
are no longer needed by the body.




Dr Atef Masad       Renal Function              5
•The central portion of the kidney consists of 
tubules that drain the kidney cortex and 
medulla. 
•The cortex, or outer portion of the kidney, 
appears red and contains the blood vessels, 
which bring blood to the kidney, and nephrons, 
the functional units that filter and maintain the 
chemical stasis of the blood. 
•The medulla appears as a series of pyramids 
within the cortex and contains straight tubules 
and collecting ducts.



Dr Atef Masad        Renal Function                  6
  •There are about 1 million nephons in each 
  kidney. 
  •In association with blood vessels that serve 
  the kidney, the nephrons make up the cortex 
  and medulla of the kidney.
  •Each nephron contains a glomerulus, 
  proximal tubule, loop of Henle, distal tubule 
  and collecting duct. 
  •The glomerulus filters blood plasma from 
  arterioles into Bowman’s space and hence in 
  the proximal tubule of the nephron. 



Dr Atef Masad        Renal Function                7
                           The Nephron

                                                 Proximal tubule
Afferent arteriole
                                                   Distal tubule
        Glomerulus
Bowman’s capsule
                                                  Collecting duct


Renal artery

                 Henle’s Loop


 Dr Atef Masad                  Renal Function                 8
•Renal Physiology
• 3 basic renal processes  
• Glomerular filtration,
•Tubular reabsorption,
•Tubular secretion.

•Glomerular filtration
•Glomerulus filters incoming blood, all substances 
except cells and large molecules pass into further 
sections of the nephron. 
•Filtration process  requires adequate pressure.
•Water, electrolytes, glucose, amino acids, urea, 
creatinine pass freely and enter the proximal tubule.
 
Dr Atef Masad         Renal Function             9
•The integrity of the glomerulus membrane, which 
consists of the endothelium, basement membrane, 
and epithelium, and renal blood flow determine the 
glomerular filtration rate.
•The glomerulus has multiple small pores through 
which chemicals are filtered from the blood. 
•In a healthy kidney, the pores exclude any 
substance with a molecular radius more than 4 nm.
•The glomerulus also selects by charge.
•Substances that are neutral or have positive 
charge are more likely to pass through the pores of 
the glomerulus than substances that are negatively 
charged. 
Dr Atef Masad       Renal Function             10
•For example, albumin, which has a molecular 
radius of less than 4 nm but is negatively charged, 
does not readily pass through the pores of the 
glomerulus.
• In a healthy kidney, cellular blood components 
should be excluded from the filtrate because of their 
size.
•Albumin, many plasma proteins, cellular elements, 
protein-bound substances such as lipids and 
bilirubin are stopped.




 Dr Atef Masad        Renal Function             11
     •"GFR"
     •The kidneys receive each minute 1500-
     2000 ml of blood, the glomerulus filters out 
     125-130 ml protein and cell free. 
     •The volume of blood filtered per minute is 
     known as the glomerulus filtration rate 




Dr Atef Masad          Renal Function                12
                      Glomerular filtration

                                  Glomerlular
 Vascular space
 Vascular space                    capillary            Bowman’s space
                                                        Bowman’s space
                                  membrane

                             Mean capillary blood
                             pressure = 50 mm Hg


 ~ 2,000 Liters                                            ~ 200 Liters
                              BC pressure = 10 mm Hg
    per day                                                  per day
(25% of cardiac output)
                             Onc. pressure = 30 mm Hg


                          Net hydrostatic = 10 mm Hg
                                                        GFR @ 130 mL/min
  Dr Atef Masad                  Renal Function                      13
                Then what happens?
• If 200 liters of filtrate enter the nephrons 
  each day, but only 1-2 liters of urine result, 
  then obviously most of the filtrate (99+ %) 
  is reabsorbed.
• Reabsorption can be active or passive, 
  and occurs in virtually all segments of the 
  nephron.




Dr Atef Masad         Renal Function                14
   Reabsorption from glomerular filtrate




Dr Atef Masad      Renal Function          15
        What gets filtered in the glomerulus?

• Freely filtered • Some filtered          • None filtered
   – H 2O            – b 2-                   – Immunoglobulins
   – Na+, K+, Cl-,     microglobulin          – Ferritin
     HCO3-, Ca++,    – a 1-                   – Cells
     Mg+, PO4, etc.    microglobulin
   – Glucose         – Albumin
   – Urea
   – Creatinine
   – Insulin


   Dr Atef Masad          Renal Function                  16
 Proximal Convoluted Tubule

 •It returns valuable substances back to the 
 blood circulation, this includes ¾ of the water.
 •Renal threshold for each substance 
 determines whether it is reabsorbed or 
 secreted. 
 •However, some substances have no renal 
 threshold e.g H2O.
 •Proximal tubule secrets products of kidney 
 tubular cell metabolism such as H+


Dr Atef Masad        Renal Function                 17
• Reabsorption may be active or passive
   – Active — against a concentration
     gradient (glucose, amino acids, low mw
     proteins, sodium, etc.) —
   – regulated by the kidney according to the
     level of these substances in the blood
   – Passive — no energy involved — such as
     water and urea
• Tubular secretion may also be passive
  or active
•Henle's Loop
•The hyperosmolality (solute concentration ) is
maintained by the Henle's loop.
•The descending limb is permeable to water but not to
solute.
•Passive reabsorption of water in descending loop
•The ascending limb is impermeable to water but
permeable to Na, Cl and partially permeable to urea.
•The medullary interstitial fluid becomes hyperosmotic
compared to the fluid in the ascending limb.
•The high osmolality of the surrounding interstitial
medulla fluid is the physical force that accelerates the
absorption of water from the descending limb.




  Dr Atef Masad         Renal Function              19
                                 The Loop of Henle

     Proximal tubule                                                              Distal tubule

                                                                                    Renal Cortex
        Increasing osmolality




                                                                            Na+
                                                                           Na+
                                                                                    300 mOsm/Kg

                                        Descending loop

                                                          Ascending loop
                                H2O                                         Na+
                                                                           Na+


                                                                            Na+
                                                                           Na+

                                                                                   Renal Medulla
                                                                                   1200 mOsm/Kg
Dr Atef Masad                         Renal Function                                               20
     •The interstitial hyperosmolality is 
     maintained because the ascending limb 
     continues to pump  Cl– and Na+ ions into 
     it.
     •The net result is production of 
     hypoosmolal urine as it leaves the loop. 
     •This process is called countercurrent 
     multiplier system.




Dr Atef Masad         Renal Function             21
•Distal Convoluted Tubule
•Small adjustments occur to achieve electrolyte  
and acid-base homeostasis.
•It is under the control of aldosterone.
•Aldosterone stimulates Na+ reabsorption by distal 
tubule and K and H+ ion secretion.
•H+ ions secretion is linked to bicarbonate 
regeneration and ammonia secretion which occur 
here, small amounts of Cl– are reabsorbed.




 Dr Atef Masad        Renal Function            22
Collecting Duct
•Is the final site for either concentrating urine or 
diluting it.
•The upper portion is under the control of 
aldosterone which acts to stimulate Na 
reabsorption. 
•Cl and urea are absorbed here.
•The collecting duct is under the control of ADH 
which stimulates water reabsorption.



Dr Atef Masad          Renal Function               23
Dr Atef Masad   Renal Function   24
•Water Balance
•Water loss is under the control of ADH.
•ADH responds primarily to changes in osmolality 
and intravascular volume.
•Increased osmolality stimulates ADH secretion 
which increases the permeability of collecting 
tubules to water resulting in more concentrated 
urine.
•In dehydration, reabsorption of water is increased, 
•In states of water excess, tubules reabsorb water 
at only a minimal rate resulting in excretion of large 
volume of dilute urine.


Dr Atef Masad           Renal Function                25
           Regulation of H2O reabsorption

                         Pituitary
                                    Plasma
                                    hyperosmolality

                               ADH (vasopressin)



                         H2O                    H2O


                Renal Medulla (osmolality »1200 mOsm/Kg)

Dr Atef Masad                  Renal Function              26
     Acid-Base Balance
     •The renal system participates in 
     controlling body pH in addition to 
     respiratory system and the acid-base 
     buffering system.
     •The kidneys role in controlling body pH 
     is accomplished by preserving HCO3– 
     and removing metabolic acids.




Dr Atef Masad          Renal Function            27
•Regeneration of HCO3–
•HCO3– are filtered by the glomerulus.
•HCO3– combines with H+ in the lumen of renal 
tubules to form H2CO3.
•H2CO3 is degraded to CO2 + H2O.
•CO2 diffuses into proximal tubules and is 
converted to H2CO3 by the action of carbonic 
anhydrase, then it is degraded back to H+ and 
HCO3.
•This regenerated HCO3 is transported into the 
blood to replace the depleted one by metabolism, 
H+ are secreted into the tubular lumen and enter 
the urine.
 Dr Atef Masad       Renal Function            28
•Reaction with NH3
•NH3 is formed in the renal tubules as a result of 
glutamine deamination by glutaminase, NH3 then 
react with H+ to form NH4 which is excreted in 
urine.
                   Glutaminase
•Glutamine   ¾¾¾¾®   glutamic acid + NH3
• NH3 + H+ + NaCl ¾¾® NH4 Cl + Na+
•This mode of acid excretion is the primary means 
by which the kidneys compensate for states of 
metabolic acidosis.



Dr Atef Masad        Renal Function             29
Reaction with Monohydrogen phosphate
"HPO42–
•Phosphate ions filtered by glomerulus exist in 
tubular fluid as Na2HPo4 which can react with H+ 
to yield NaH2 Po4 + Na. 
•Na2HPo4 is excreted, it is responsible for the 
titratable acidity of the urine.
•The released Na combines with HCO3– to yield 
NaHCO3 which is reabsorbed.



Dr Atef Masad       Renal Function             30
•Sodium is exchanged in the presence of the 
hormone aldosterone and water is exchanged in 
the presence of antidiuretic hormone (ADH). 
•The exchange of chemicals back into the blood 
supply is called reabsorption.

•Exchange may occur as active transport, or as 
passive transport, which occurs with the gradient 
from high to low concentration of the chemical.

•Some tubule cells, especially those in the distal 
portion of the nephron, exchange sodium and 
water back into the blood supply. 
 Dr Atef Masad        Renal Function              31
 •Because of the ability of the nephron to filter 
 and reabsorb certain chemicals from the blood, 
 the measurement of the concentration of these 
 chemicals in the blood and urine serves as a
 functional evaluation of the kidney and specific
 areas of the nephron.

 •The measurements of the concentrations of
 creatinine, blood urea nitrogen, and electrolytes
 all serve as functional evaluations of different
 areas of the kidney.



Dr Atef Masad        Renal Function                 32
  Renal Endocrine Function
  • (A) Primary endocrine function
  •The kidneys synthesize rennin, prostaglandin 
  and erythropoietin.
  •1- Rennin
  •Rennin is produced by renal medulla 
  whenever extracellular fluid volume 
  decreases.
  •It is responsive to changes in Na+ and K+ 
  levels in blood.



Dr Atef Masad       Renal Function             33
• It is vasoconstrictor which increases blood
  pressure.
• It catalyzes the synthesis of angiotensin by
  means of cleavage of the circulating
  plasma precursor angiotensinogen.
Regulation of distal tubule Na+ permeability

     ¯ Na+
                Renin     Angiotensinogen
     ¯ BP
                          Angiotensin I
                          Angiotensin II       vasoconstriction
                          Angiotensin III
                                               Adrenal cortex
                           Aldosterone

                        Na+                         Na+



Dr Atef Masad                 Renal Function                35
ANP acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing blood
pressure, ACE angiotensin converting enzyme
   Dr Atef Masad                               Renal Function                                            36
      Atrial natriuretic peptide (ANP), 
      is a powerful vasodilator hormone secreted by 
      heart muscle cells. ANP acts to reduce the 
      water, sodium and adipose loads on the 
      circulatory system, thereby reducing blood 
      pressure




Dr Atef Masad          Renal Function            37
• 2- Prostaglandins
• Prostaglandins produced by kidneys
  increase renal blood flow, Na and H2O
  excretion and rennin discharge.
• They resist renal vasoconstriction due to
  angiotensin and norepinephrine.
• Prostaglandins are used in
  antihypertensive therapy.
•3- Erythropoietin
•It is a single chain polypeptide.
•It is produced by cells close to the proximal 
tubules.
•Its production is regulated by blood oxygen levels 
"hypoxia increases its production".
•Erythropoietin acts on the erythroid progenitor 
cells in the bone marrow, causing their maturation 
and increasing the number of RBCs.
•In chronic renal insufficiency, erythropoietin 
production is significantly reduced causing 
anemia.


Dr Atef Masad        Renal Function             39
 •(B) Secondary Endocrine Function
 •The kidneys are the target locus for the 
 action of aldosterone, the catabolism of 
 insulin, glucagons and aldosterone and as a 
 point of activation of vitamin D metabolism.




Dr Atef Masad       Renal Function              40
            Renal Disorders

     • Acute Glomerulonephritis
     • Nephrotic Syndrome
     • Tubular Diseases
     • Urinary Tract Infection
     • Acute Renal Failure



41
         Acute Glomerulonephritis
     • Acute inflammation of the glomeruli
     • Results in oliguria, hematuria, increased BUN
       and serum creatinine, decreased GFR and
       hypertension
     • Red cell cast finding are of great importance
     • Proteinuria also present




                                      Red cell cast
42
             Nephrotic Syndrome
     • Massive proteinuria, edema, hypoalbuminemia,
       hyperlipidemia, and lipiduria
     • Has many cuases
     • Characterized by increased glomerular
       membrane permeability — loss of protein
       (greater than 2-3 grams per day)




43
                Tubular Diseases

     • Depressed secretion or reabsorption of specific
       biochemicals
     • Or Impairment of urine dilution and
       concentration mechanisms
     • Renal Tubular Acidosis — most important
     • Low values of phosphorus in serum, and
       presence of glucose and AA in urine




44
            Urinary Tract Infection

     • Bladder — cystitis
     • Kidneys — pyelonephritis
     • Bacterial concentrations >100,000
       colonies/mL
     • Increased number of white blood
       cells
     • Increased number of red blood cells
       may be present
     • White blood cell casts is considered
       diagnostic of pyelonephritis


45
             Acute Renal Failure
     • Ocurring when the GFR is reduced to less
       than 10 mL/minute.
     • Prerenal — before blood reaches the kidney
       – Hypovolemia
       – Cardiovascular failure
     • Renal — occuring in kidney
       – Acute tubular necrosis
       – Glomerulonephritis
     • Postrenal — after urine leaves kidney
       – Obstruction


46
     • Usually accompanied by oliguria
     • Associated with varying degrees of
       proteinuria, hematuria, and presence of
       red cell casts and other casts
     • BUN and creatinine increase rapidly
     • Can progress to chronic renal insufficiency
       or failure




47
                Renal Calculi

• Formed by the combination of various crystallized
  substances.
• Such as Ca-phospahte, Uric Acid, Cystine, Mg-
  ammonium phosphate and Ca-oxalate
• Calcium oxalate stones are the most common.
• Formed due a reduced urine flow rate due to
  decrease fluid intake and urine saturation of
  insoluble substances, ifections, Gout, inherited
  diseases, Hyperparathyroidism, high urine Ca,
  Vitamin D toxicity
• Chemical analysis is available and x
  ray diffraction.
• Clinical symptoms: hematuria, UTI,
  and abdominal pain

				
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