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Chapter 4 Renal Function

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Title: Interpretation of Laboratory Tests: A Case-Oriented Review of Clinical Laboratory Diagnosis Author: Roger L. Bertholf Last modified by: atef – PowerPoint PPT presentation

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Title: Chapter 4 Renal Function


1
Chapter 4 Renal Function
Dr Atef A Masad
2
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

3
  • 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.

4
Renal anatomy
Cortex
Pelvis
Capsule
Medulla
To the bladder
5
  • 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.

6
  • 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.

7
  • 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 Bowmans space and hence in the
    proximal tubule of the nephron.

8
The Nephron
9
  • 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.
  •  

10
  • 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.

11
  • 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.

12
  • "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

13
Glomerular filtration
Glomerlular capillary membrane
Vascular space
Bowmans space
? 2,000 Liters per day (25 of cardiac output)
? 200 Liters per day
GFR ? 130 mL/min
14
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.

15
Reabsorption from glomerular filtrate
16
What gets filtered in the glomerulus?
  • Freely filtered
  • H2O
  • Na, K, Cl-, HCO3-, Ca, Mg, PO4, etc.
  • Glucose
  • Urea
  • Creatinine
  • Insulin
  • Some filtered
  • ?2-microglobulin
  • ?1-microglobulin
  • Albumin
  • None filtered
  • Immunoglobulins
  • Ferritin
  • Cells

17
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

18
  • 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

19
  • 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.

20
The Loop of Henle
Proximal tubule
Distal tubule
Renal Cortex
Descending loop
Ascending loop
Renal Medulla
21
  • 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.

22
  • 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.

23
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.

24
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25
  • 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.

26
Regulation of H2O reabsorption
Pituitary
Renal Medulla (osmolality ?1200 mOsm/Kg)
27
  • 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.

28
  • 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.

29
  • 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 ????? glutamic acid NH3
  • NH3 H NaCl ??? NH4 Cl Na
  • This mode of acid excretion is the primary means
    by which the kidneys compensate for states of
    metabolic acidosis.

30
  • 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.

31
  • 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.

32
  • 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.

33
  • 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.

34
  • It is vasoconstrictor which increases blood
    pressure.
  • It catalyzes the synthesis of angiotensin by
    means of cleavage of the circulating plasma
    precursor angiotensinogen.

35
Regulation of distal tubule Na permeability
36
ANP acts to reduce the water, sodium and adipose
loads on the circulatory system, thereby reducing
blood pressure, ACE angiotensin converting enzyme
37
  • 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

38
  • 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.

39
  • 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.

40
  • (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.

41
Renal Disorders
  • Acute Glomerulonephritis
  • Nephrotic Syndrome
  • Tubular Diseases
  • Urinary Tract Infection
  • Acute Renal Failure

41
M. Zaharna Clin. Chem. 2009
42
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
M. Zaharna Clin. Chem. 2009
43
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
M. Zaharna Clin. Chem. 2009
44
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
M. Zaharna Clin. Chem. 2009
45
Urinary Tract Infection
  • Bladder cystitis
  • Kidneys pyelonephritis
  • Bacterial concentrations gt100,000 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
M. Zaharna Clin. Chem. 2009
46
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
M. Zaharna Clin. Chem. 2009
47
  • 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
M. Zaharna Clin. Chem. 2009
48
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

49
  • Chemical analysis is available and x ray
    diffraction.
  • Clinical symptoms hematuria, UTI, and abdominal
    pain
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