Transcript Interpretation of Laboratory Tests: A Case

Chapter 4
Renal Function
Dr Atef A Masad
Dr Atef Masad
Renal Function
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What do the kidneys do?
• Urine formation
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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
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•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.
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Renal anatomy
Cortex
Pelvis
Capsule
Medulla
To the bladder
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•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.
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•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.
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•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.
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The Nephron
Proximal tubule
Afferent arteriole
Distal tubule
Glomerulus
Bowman’s capsule
Collecting duct
Renal artery
Henle’s Loop
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•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.
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•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.
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•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.
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•"GFR"
•The kidneys receive each minute 15002000 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
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Glomerular filtration
Vascular space
Glomerlular
capillary
membrane
Bowman’s space
Mean capillary blood
pressure = 50 mm Hg
 2,000 Liters
per day
BC pressure = 10 mm Hg
 200 Liters
per day
(25% of cardiac output)
Onc. pressure = 30 mm Hg
Net hydrostatic = 10 mm Hg
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GFR  130 mL/min
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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.
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Reabsorption from glomerular filtrate
% Reabsorbed
Water
Sodium
Potassium
Chloride
Bicarbonate
Glucose
Albumin
Urea
Creatinine
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99.2
99.6
92.9
99.5
99.9
100
95-99
50-60
0 (or negative)
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What gets filtered in the glomerulus?
• Freely filtered • Some filtered
– H2O
–  2microglobulin
– Na+, K+, Cl-,
HCO3-, Ca++,
– 1Mg+, PO4, etc.
microglobulin
– Glucose
– Albumin
– Urea
– Creatinine
– Insulin
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• None filtered
– Immunoglobulins
– Ferritin
– Cells
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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+
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• 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.
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The Loop of Henle
Proximal tubule
Distal tubule
Ascending loop
H2O
Descending loop
Increasing osmolality
Na+
Renal Cortex
300 mOsm/Kg
Na+
Na+
Renal Medulla
1200 mOsm/Kg
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•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.
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•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.
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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.
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•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.
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Regulation of H2O reabsorption
Pituitary
Plasma
hyperosmolality
ADH (vasopressin)
H2O
H2O
Renal Medulla (osmolality 1200 mOsm/Kg)
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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.
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•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.
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•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.
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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.
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•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.
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•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.
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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.
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• 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+
 BP
Renin
Angiotensinogen
Angiotensin I
Angiotensin II
vasoconstriction
Angiotensin III
Aldosterone
Adrenal cortex
Na+
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Na+
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ANP acts to reduce the water, sodium and adipose loads on the circulatory system, thereby reducing blood
pressure, ACE angiotensin converting enzyme
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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
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• 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.
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•(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.
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Renal Disorders
• Acute Glomerulonephritis
• Nephrotic Syndrome
• Tubular Diseases
• Urinary Tract Infection
• Acute Renal Failure
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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
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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)
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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
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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
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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
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• 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
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Renal Calculi
• Formed by the combination of various crystallized
substances.
• Such as Ca-phospahte, Uric Acid, Cystine, Mgammonium 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