kidney 2 By

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kidney 2By

• Mona Abu Bakr El-Hussiny
• Assistant Lecturer of Clinical Pathology,
  Clinical Pathology Department,
• Faculty of Medicine Mansoura University

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THE FORMATION OF URINEFIGURATION,
REABSORPTION, AND SECRETION

• Every one of us depends on the process of
  urination for the removal of certain waste
  products in the body. The production of urine is
  vital to the health of the body. Urine is
  composed of water, certain electrolytes, and
  various waste products that are filtered out of
  the blood system.

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• Remember, as the blood flows through the body,
  wastes resulting from the metabolism of
  foodstuffs in the body cells are deposited into
  the bloodstream, and this waste must be disposed
  of in some way. A major part of this "cleaning"
  of the blood takes place in the kidneys and, in
  particular, in the nephrons, where the blood is
  filtered to produce the urine. Both kidneys in
  the body carry out this essential blood cleansing
  function. Normally, about 20 of the total blood
  pumped by the heart each minute will enter the
  kidneys to undergo filtration. This is called the
  filtration fraction.

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Filtration

• Urine formation begins with the process of which
  goes on continually in the renal corpuscles. As
  blood courses through the glomeruli, much of its
  fluid, containing both useful chemicals and
  dissolved waste materials, soaks out of the blood
  through the membranes (by osmosis and diffusion)
  where it is filtered and then flows into the
  Bowman's capsule.

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• This process is called glomerular filtration. The
  water, waste products, salt, glucose, and other
  chemicals that have been filtered out of the
  blood are known collectively as glomerular
  filtrate. The glomerular filtrate consists
  primarily of water, excess salts (primarily Na
  and K), glucose, and a waste product of the body
  called urea.

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• Urea is formed in the body to eliminate the very
  toxic ammonia products that are formed in the
  liver from amino acids. Since humans cannot
  excrete ammonia, it is converted to the less
  dangerous urea and then filtered out of the
  blood.

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• Urea is the most abundant of the waste products
  that must be excreted by the kidneys. The total
  rate of glomerular filtration (glomerular
  filtration rate or GFR) for the whole body (i.e.,
  for all of the nephrons in both kidneys) is
  normally about 125 ml per minute. That is, about
  125 ml of water and dissolved substances are
  filtered out of the blood per minute

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• glomerular filtration rateglumerular pressure
• ( osmotic pressure Bomans capsular pressure).
• The first process in urine formation, returns to
  the blood by the second process - reabsorption.

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Reabsorption

• Reabsorption, by definition, is the movement of
  substances out of the renal tubules back into the
  blood capillaries located around the tubules.
  Substances reabsorbed are water, glucose and
  other nutrients, and sodium (Na) and other ions.
  Reabsorption begins in the proximal convoluted
  tubules and continues in the loop of Henle,
  distal convoluted tubules, and collecting
  tubules.

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• Large amounts of water - more than 178 liters per
  day - are reabsorbed back into the bloodstream
  from the proximal tubules because the physical
  forces acting on the water in these tubules
  actually push most of the water back into the
  blood capillaries. In other words, about 99 of
  the 180 liters of water that leave the blood each
  day by glomerular filtration returns to the blood
  from the proximal tubule through the process of
  passive reabsorption.

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• The nutrient glucose (blood sugar) is entirely
  reabsorbed back into the blood from the proximal
  tubules. In fact, it is actively transported out
  of the tubules and into the peritubular capillary
  blood. None of this valuable nutrient is wasted
  by being lost in the urine. However, even when
  the kidneys are operating at peak efficiency, the
  nephrons can reabsorb only so much sugar and
  water

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• Their limitations are dramatically illustrated in
  cases of diabetes mellitus, a disease which
  causes the amount of sugar in the blood to rise
  far above normal. As already mentioned, in
  ordinary cases all the glucose that seeps out
  through the glomeruli into the tubules is
  reabsorbed into the blood.

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• But if too much is present, the tubules reach the
  limit of their ability to pass the sugar back
  into the bloodstream, and the tubules retain some
  of it. It is then carried along in the urine,
  often providing a doctor with her first clue that
  a patient has diabetes mellitus.

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• Sodium ions (Na) and other ions are only
  partially reabsorbed from the renal tubules back
  into the blood. For the most part, however,
  sodium ions are actively transported back into
  blood from the tubular fluid. The amount of
  sodium reabsorbed varies from time to time it
  depends largely on how much salt we take in the
  foods that we eat.

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• As a person increases the amount of salt taken
  into the body, that person's kidneys decrease the
  amount of sodium reabsorption back into the
  blood. That is, more sodium is retained in the
  tubules. Therefore, the amount of salt excreted
  in the urine increases. The less the salt intake,
  the greater the amount of sodium reabsorbed back
  into the blood, and the amount of salt excreted
  in the urine decreases.

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Secretion

• Secretion is the process by which substances move
  into the distal and collecting tubules from blood
  in the capillaries around these tubules. In this
  respect, secretion is reabsorption in reverse.
  Whereas reabsorption moves substances out of the
  tubules and into the blood, secretion moves
  substances out of the blood and into the tubules
  where they mix with the water and other wastes
  and are converted into urine

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• These substances are secreted through either an
  active transport mechanism or as a result of
  diffusion across the membrane. Substances
  secreted are hydrogen ions (H), potassium ions
  (K), ammonia (NH3), and certain drugs. Kidney
  tubule secretion plays a crucial role in
  maintaining the body's acid-base balance, another
  example of an important body function that the
  kidney participates in.

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Extracellular homeostasisThe kidney is
responsible for maintaining a balance of several
substances
Collecting duct Distal tubule Loop of Henle Proximal tubule Description Substance
reabsorption (almost 100) via sodium-glucose transport proteins (apical) and GLUT (basolateral). If glucose is not reabsorbed by the kidney, it appears in the urine, in a condition known as glucosuria. This is associated with diabetes mellitus Glucose
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reabsorption All are reabsorbed nearly completely Oligopeptides, proteins, and amino acids
reabsorption in medullary collecting ducts secretion reabsorption (50) via passive transport Regulation of osmolality. Varies with ADH Urea
reabsorption (5, reabsorption (5, reabsorption (25, thick reabsorption Uses Na-H antiport, Na Sodium
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principal cells), stimulated by aldosterone sodium-chloride symporter) ascending, Na-K-2Cl symporter) 65 isosmotic glucose symport, sodium ion channels (minor)
reabsorption (sodium-chloride symporter) reabsorption (thin ascending, thick ascending, Na-K-2Cl symporter) reabsorption Usually follows sodium. Active (transcellular) and passive (paracellular) Chloride
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reabsorption (regulated by ADH, via arginine vasopressin receptor 2) reabsorption (descending) absorbed osmotically along with solutes Uses aquaporin water channels. See also diuretic Water
reabsorption (intercalated cells, via band 3 and pendrin) reabsorption (thick ascending) reabsorption (80-90) Helps maintain acid-base balance. Bicarbonate
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secretion (common, via Na/K-ATPase, increased by aldosterone), or reabsorption (rare, hydrogen potassium ATPase reabsorption (20, thick ascending, Na-K-2Cl symporter) reabsorption (65) Varies upon dietary needs Potassium
reabsorption (thick ascending) via passive transport reabsorption Uses calcium ATPase, sodium-calcium exchanger Calcium
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reabsorption reabsorption (thick ascending) reabsorption Calcium and magnesium compete, and an excess of one can lead to excretion of the other. Magnesium
reabsorption (85) via sodium/phosphate cotransporter Inhibited by parathyroid hormone Excreted as titratable acid Phosphate
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Acid base homeostasis

• The body is very sensitive to its pH level.
  Outside the range of pH that is compatible with
  life, proteins are denatured and digested,
  enzymes lose their ability to function, and the
  body is unable to sustain itself. The kidneys
  maintain acid-base homeostasis by regulating the
  pH of the blood plasma. Gains and losses of acid
  and base must be balanced. Acids are divided into
  "volatile acids" and "nonvolatile acids".

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• About 90 of filtered bicarbonate is reabsorbed
  in PCT with the remaindered reabsorbed in the
  DCT and CD. In the PCT this is a consequence of H
  ion secretion and the action of the enzyme
  carbonic anhydrase. In the DCT , after the
  bicarbonate has been predominantly removed,
  secreted H ions are taken up by other buffers as
  phosphate . in most part of nephrone,
  predominantly in the PCT, ammonium ions are
  generated as the result of deammination of
  glutamine. The ammonium ions is secreted into the
  tubular lumin, generating intracellular
  bicarbonate.

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Water homeostasis

• Water homeostasis is determined by
• water intake
• extrarenal water loss.
• Solute load
• Kidney ability to produce concentrated or diluted
  urine

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• The minimum urine volume is determined by solute
  load to be excreted and may be as low as 400 ml/
  d.
• The maximum urine volume is determined by water
  load to be excreted and may be as mnch as 20-25
  L/ d.

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• Osmolal clearance ( C osm) represent volume of
  urine that would be required for isoosmolal
  clearance of solute load.

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Negative free water clearance Free water clearance
Measure concentrating ability Water reabsorbed from tubular fluid during production of concetrated hypertonic urine C H2O C osmo - V Difference between actual urine flow rate and flow rate calculated for isosmotic excretion . Measure diluting ability In excess that required for isoosmolal urine C H2O V-C osmo
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• Two main process are involved in in water
  reabsorption
• Isosmotic reabsorption of water from PCT
• About 80 returned to the body by PCT
• Active solute reabsorption from the filterate
  is accompanied by passive reabsorption of an
  osmotically equivelant amount of water
• Differential reabsorption of water and solute
  from the loop of Henle, DCT, CD two mechanism
  are involved

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Countercurrent exchange Countercurrent multiplication
Passive process In DCT and CD In presence of ADH In abscence of ADH the collecting duct impermeable to water Produce conc.urine and plasma is diluted Active process In loop of Henle In absence of ADH Lead to production of diluted urine (low osmolarity) and increase plasma osmolality.( in loop of Henle reab of Na Cl without water).
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Endocrine function
Renine erythropoietin- prostaglandins- kinin-vit D- natriuretic peptides Hormones produced by the kidne
Aldosterone- PTH- ADH- calcitonin- natriuretic H- thyroid H- glucocorticoid- somatomedin. Hormones that control kidney function
PTH- calcitonin- insulin- somatomedin- GIT hormones- vasopressin- hypothamic RH- prolactin- angiotensin II. Hormones catabolised by the kidney
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Aldosterone

• Aldosterone is a steroid hormone
  (mineralocorticoid family) produced by the
  outer-section (zona glomerulosa) of the adrenal
  cortex in the adrenal gland, and acts on the
  distal tubules and collecting ducts of the kidney
  to cause the conservation of sodium, secretion of
  potassium, increased water retention, and
  increased blood pressure. Aldosterone is part of
  the renin-angiotensin system.
• Its activity is reduced in Addison's disease
  and increased in Conn syndrome.

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vasopressin

• Arginine vasopressin (AVP), also known as
  vasopressin, argipressin or antidiuretic hormone
  (ADH), is a hormone found in most mammals,
  including humans.1 Vasopressin is a peptide
  hormone. It is derived from a preprohormone
  precursor that is synthesized in the hypothalamus
  and stored in vesicles at the posterior
  pituitary.

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vasopressin

• Arginine vasopressin (AVP), also known as
  vasopressin, argipressin or antidiuretic hormone
  (ADH), is a hormone found in most mammals,
  including humans.1 Vasopressin is a peptide
  hormone. It is derived from a preprohormone
  precursor that is synthesized in the hypothalamus
  and stored in vesicles at the posterior
  pituitary.

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• One of the most important roles of AVP is to
  regulate the body's retention of water it is
  released when the body is dehydrated and causes
  the kidneys to conserve water, thus concentrating
  the urine, and reducing urine volume. In high
  concentrations, it also raises blood pressure by
  inducing moderate vasoconstriction.

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• AVP increases the permeability to water of the
  distal convoluted tubules and collecting tubules
  in the nephrons of kidneys and thus allows water
  reabsorption and excretion of a smaller volume of
  concentrated urine - antidiuresis. This occurs
  through insertion of additional water channels
  (Aquaporin-2s) into the apical membrane of the
  tubules/collecting duct epithelial cells. The
  aquaporins allow water to pass out of the nephron
  (at the distal convoluted tubules and the
  conducting tubules) and into the cells,
  increasing the amount of water re-absorbed from
  the filtrate

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Erythropoietin or EPO

• Is a glycoprotein hormone that controls
  erythropoiesis, or red blood cell production. It
  is a cytokine for erythrocyte (red blood cell)
  precursors in the bone marrow. It is produced by
  the kidney, and is the hormone that regulates red
  blood cell production. It also has other known
  biological functions. For example, erythropoietin
  plays an important role in the brain's response
  to neuronal injury. EPO is also involved in the
  wound healing process.

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• An intermediate is created by phospholipase-A2,
  then passed into one of either the cyclooxygenase
  pathway or the lipoxygenase pathway to form
  either prostaglandin and thromboxane or
  leukotriene. The cyclooxygenase pathway produces
  thromboxane, prostacyclin and prostaglandin D, E
  and F. The lipoxygenase pathway is active in
  leukocytes and in macrophages and synthesizes
  leukotrienes.

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Types

• Following is a comparison of the prostaglandin
  types Prostaglandin I2 (PGI2), Prostaglandin E2
  (PGE2) and Prostaglandin F2a (PGF2a).

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Function Receptor Type
vasodilation inhibit platelet aggregation bronchodilatation IP PGI2
bronchoconstriction GI tract smooth muscle contraction EP1 PGE2
bronchodilatation GI tract smooth muscle relaxation vasodilatation EP2 PGE2
? gastric acid secretion ? gastric mucus secretion uterus contraction (when pregnant) GI tract smooth muscle contraction lipolysis inhibition EP3 PGE2
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? autonomic neurotransmitters 6
hyperalgesia6 pyrogenic Unspecified
uterus contraction bronchoconstriction FP PGF2a
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Vitamin D

• Vitamin D3 has several forms
• Cholecalciferol, (which is an inactive,
  unhydroxylated form of vitamin D3)
• Calcidiol (also called 25-hydroxyvitamin D3),
  which is the form measured in the blood to assess
  vitamin D status
• Calcitriol (also called 1,25-dihydroxyvitamin
  D3), which is the active form of D3.

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• is a form of Vitamin D3 with three alcohol
  groups. It increases gastrointestinal Calcium
  absorption, stimulates osteoclastic Calcium
  resorption from bone, facilitates the effect
  Parathyroid Hormone (PTH) has on bone resorption,
  and increases renal tubular absorption of
  Calcium. Production of Calcitriol by the cells of
  the Proximal Tubule of the nephron in the kidney
  is stimulated by hypocalcemia and hypophospatemia.

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Metabolism

• 7-Dehydrocholesterol is the precursor of
  vitamin D3 and forms cholecalciferol only after
  being exposed to solar UV radiation.
• Cholecalciferol is then hydroxylated in the
  liver to become calcidiol (25-hydroxyvitamin D3).
• Next, calcidiol is again hydroxylated, this
  time in the kidney, and becomes calcitriol
  (1,25-dihydroxyvitamin D3). Calcitriol is the
  most active hormone form of vitamin D3.

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Laboratory tests

• Glomerular function tests
• clearance
• Creatinine clearance test.
• This test evaluates how efficiently the kidneys
  clear a substance called creatinine from the
  blood. Creatinine, a waste product of muscle
  energy metabolism, is produced at a constant rate
  that is proportional to the individual's muscle
  mass. Because the body does not recycle it, all
  creatinine filtered by the kidneys in a given
  amount of time is excreted in the urine, making
  creatinine clearance a very specific measurement
  of kidney function. The test is performed on a
  timed urine specimena cumulative sample
  collected over a two to 24-hour period.
  Determination of the blood creatinine level is
  also required to calculate the urine clearance.

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• Calculation of CCr
• The urinary flow rate is still calculated per
  minute, hence

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• To allow comparison of results between people of
  different sizes, the CCr is often corrected for
  the body surface area (BSA) and expressed
  compared to the average sized man as mL/min/1.73
  m2. While most adults have a BSA that approaches
  1.7 (1.6-1.9), extremely obese or slim patients
  should have their CCr corrected for their actual
  BSA