kidney 2kidney 2ByBy

Mona Abu Bakr El-Hussiny

Assistant Lecturer of Clinical Pathology, Clinical

Pathology Department,

Faculty of Medicine –Mansoura University

Renal function

excretory regulatory endocrine

THE FORMATION OF URINETHE FORMATION OF URINE

FIGURATION, REABSORPTION, AND FIGURATION, REABSORPTION, AND SECRETIONSECRETION

Every one of us depends on the process of urination for Every one of us depends on the process of urination for

the removal of certain waste products in the body. The the removal of certain waste products in the body. The

production of urine is vital to the health of the body. production of urine is vital to the health of the body.

Urine is composed of water, certain electrolytes, and Urine is composed of water, certain electrolytes, and

various waste products that are filtered out of the various waste products that are filtered out of the

blood systemblood system..

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

filtration fractionfiltration fraction..

FiltrationFiltrationUrine formation begins with the process ofUrine formation begins with the process of

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

This process is calledThis process is called glomerular filtration. glomerular filtration.

The water, waste products, salt, glucose, The water, waste products, salt, glucose,

and other chemicals that have been filtered and other chemicals that have been filtered

out of the blood are known collectively as out of the blood are known collectively as

glomerular filtrate. The glomerular filtrate glomerular filtrate. The glomerular filtrate

consists primarily of water, excess salts consists primarily of water, excess salts

(primarily Na(primarily Na+ + and Kand K+), +), glucose, and a glucose, and a

waste product of the body calledwaste product of the body called urea. urea.

Urea is formed in the body to eliminate the Urea is formed in the body to eliminate the

very toxic ammonia products that are very toxic ammonia products that are

formed in the liver from amino acids. Since formed in the liver from amino acids. Since

humans cannot excrete ammonia, it is humans cannot excrete ammonia, it is

converted to the less dangerous urea and converted to the less dangerous urea and

then filtered out of the bloodthen filtered out of the blood. .

Urea is the most abundant of the waste Urea is the most abundant of the waste

products that must be excreted by the products that must be excreted by the

kidneys. The total rate of glomerular kidneys. The total rate of glomerular

filtrationfiltration ( (glomerular filtration rate orglomerular filtration rate or

GFR) for the whole body (i.e., for all of the GFR) for the whole body (i.e., for all of the

nephrons in both kidneys) is normally about nephrons in both kidneys) is normally about

125 ml per minute. That is, about 125 ml of 125 ml per minute. That is, about 125 ml of

water and dissolved substances are filtered water and dissolved substances are filtered

out of the blood per minute out of the blood per minute

glomerular filtration rate=glumerular pressure –glomerular filtration rate=glumerular pressure –

( osmotic pressure + Bomans capsular pressure).( osmotic pressure + Bomans capsular pressure).

The first process in urine formation, returns to The first process in urine formation, returns to

the blood by the second process - reabsorption.the blood by the second process - reabsorption.

ReabsorptionReabsorption

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

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

The nutrient glucose (blood sugar) isThe nutrient glucose (blood sugar) is entirelyentirely

reabsorbed back into the blood from the proximal reabsorbed back into the blood from the proximal

tubules. In fact, it istubules. In fact, it is actively transportedactively transported out of out of

the tubules and into the peritubular capillary the tubules and into the peritubular capillary

blood. None of this valuable nutrient is wasted by blood. None of this valuable nutrient is wasted by

being lost in the urine. However, even when the being lost in the urine. However, even when the

kidneys are operating at peak efficiency, the kidneys are operating at peak efficiency, the

nephrons can reabsorb only so much sugar and nephrons can reabsorb only so much sugar and

water water

Their limitations are dramatically illustrated in Their limitations are dramatically illustrated in

cases of diabetes mellitus, a disease which cases of diabetes mellitus, a disease which

causes the amount of sugar in the blood to rise causes the amount of sugar in the blood to rise

far above normal. As already mentioned, in far above normal. As already mentioned, in

ordinary cases all the glucose that seeps out ordinary cases all the glucose that seeps out

through the glomeruli into the tubules is through the glomeruli into the tubules is

reabsorbed into the bloodreabsorbed into the blood. .

But if too much is present, the tubules reach the But if too much is present, the tubules reach the

limit of their ability to pass the sugar back into limit of their ability to pass the sugar back into

the bloodstream, and the tubules retain some the bloodstream, and the tubules retain some

of it. It is then carried along in the urine, often of it. It is then carried along in the urine, often

providing a doctor with her first clue that a providing a doctor with her first clue that a

patient has diabetes mellituspatient has diabetes mellitus..

Sodium ions (NaSodium ions (Na+) +) and other ions are only and other ions are only

partially reabsorbed from the renal tubules partially reabsorbed from the renal tubules

back into the blood. For the most part, back into the blood. For the most part,

however, sodium ions arehowever, sodium ions are actively actively

transportedtransported back into blood from the tubular back into blood from the tubular

fluid. The amount of sodium reabsorbed varies fluid. The amount of sodium reabsorbed varies

from time to time; it depends largely on how from time to time; it depends largely on how

much salt we take in the foods that we eatmuch salt we take in the foods that we eat. .

As a person increases the amount of salt taken into the As a person increases the amount of salt taken into the

body, that person's kidneys decrease the amount of body, that person's kidneys decrease the amount of

sodium reabsorption back into the blood. That is, sodium reabsorption back into the blood. That is,

more sodium is retained in the tubules. Therefore, the more sodium is retained in the tubules. Therefore, the

amount of salt excreted in the urine increases. The amount of salt excreted in the urine increases. The

less the salt intake, the greater the amount of sodium less the salt intake, the greater the amount of sodium

reabsorbed back into the blood, and the amount of reabsorbed back into the blood, and the amount of

salt excreted in the urine decreasessalt excreted in the urine decreases. .

SecretionSecretion

SecretionSecretion is the process by which substances is the process by which substances

move into the distal and collecting tubules from move into the distal and collecting tubules from

blood in the capillaries around these tubules. In blood in the capillaries around these tubules. In

this respect, secretion is reabsorption in reverse. this respect, secretion is reabsorption in reverse.

Whereas reabsorption moves substances out of Whereas reabsorption moves substances out of

the tubules and into the blood, secretion moves the tubules and into the blood, secretion moves

substances out of the blood and into the tubules substances out of the blood and into the tubules

where they mix with the water and other wastes where they mix with the water and other wastes

and are converted into urine and are converted into urine

These substances are secreted through either anThese substances are secreted through either an

active transportactive transport mechanism or as a result of mechanism or as a result of

diffusiondiffusion across the membrane. Substances across the membrane. Substances

secreted are hydrogen ions (H+), potassium secreted are hydrogen ions (H+), potassium

ions (K+), ammonia (NH3), and certain drugs. ions (K+), ammonia (NH3), and certain drugs.

Kidney tubule secretion plays a crucial role in Kidney tubule secretion plays a crucial role in

maintaining the body's acid-base balance, maintaining the body's acid-base balance,

another example of an important body function another example of an important body function

that the kidney participates inthat the kidney participates in..

Extracellular homeostasisExtracellular homeostasisThe kidney is responsible for maintaining a The kidney is responsible for maintaining a balance of several substancesbalance of several substances::

SubstanceSubstance DescriptionDescription ProximalProximal tubule tubule

Loop of Loop of HenleHenle

Distal tuDistal tubulebule

CollectingCollecting duct duct

GlucoseGlucose If glucose is not If glucose is not

reabsorbed by reabsorbed by the kidney, it the kidney, it appears in the appears in the

urine, in a urine, in a condition condition known asknown as

glucosuriaglucosuria. This . This is associated is associated

withwith diabetes mellitdiabetes mellitusus

reabsorption reabsorption (almost (almost

100%) via100%) via sodium-glucosodium-glucose transport pse transport proteinsroteins

( (apicalapical) and) and GLUTGLUT( (

basolateralbasolateral.).)

OligopeptidesOligopeptides , ,proteinsproteins , ,andand

amino acidsamino acids

All are All are reabsorbereabsorbed nearly d nearly completelycompletely

reabsorptionreabsorption

UreaUrea Regulation Regulation ofof osmolalityosmolality. . Varies Varies

withwith ADHADH

reabsorption reabsorption (50%) via(50%) via

passive tranpassive transportsport

secretionsecretion reabsorption reabsorption inin medullarymedullary

collecting d collecting ductsucts

SodiumSodiumUsesUses Na-H Na-H antiportantiport, , NaNa

reabsorptionreabsorption reabsorption reabsorption (25%, thick(25%, thick

reabsorptioreabsorptio

n (5%n (5% , ,reabsorptioreabsorptio

n (5%n (5% , ,

glucose glucose symportsymport, , sodium ion chasodium ion channelsnnels (minor (minor) )

6565% % isosmoticisosmotic

ascendingascending, , Na-K-2Cl Na-K-2Cl symportersymporter))

sodium-chlosodium-chloride ride symportersymporter))

principal principal cells), cells), stimulated stimulated byby aldosteronealdosterone

ChlorideChloride Usually Usually followsfollows sodiumsodium. . Active Active (transcellular) (transcellular) and passiveand passive ( (paracellularparacellular) )

reabsorptioreabsorption n

reabsorptioreabsorption (thin n (thin ascending, ascending, thick thick ascendingascending, , Na-K-2Cl Na-K-2Cl symportersymporter))

reabsorptioreabsorptionn ( (sodium-chlosodium-chloride ride symportersymporter))

WaterWater

UsesUses aquaporinaquaporin water water channels. channels. See alsoSee also diureticdiuretic

absorbed absorbed osmotically osmotically along with along with solutes solutes

reabsorptioreabsorption n (descending(descending))

reabsorption reabsorption (regulated by (regulated by ADH, viaADH, via argininearginine vasopressin rec vasopressin receptor 2eptor 2))

BicarbonateBicarbonate Helps Helps maintain maintain acid-base acid-base balance. balance.

reabsorptioreabsorption (80-90%) n (80-90%)

reabsorptioreabsorption (thick n (thick ascending) ascending)

reabsorption reabsorption (intercalated (intercalated cells, via cells, via band 3band 3 and and pendrinpendrin) )

PotassiumPotassium Varies upon Varies upon dietary dietary needs needs

reabsorptioreabsorption (65%) n (65%)

reabsorptioreabsorption (20%, n (20%, thick thick ascending, ascending, Na-K-2Cl Na-K-2Cl symportersymporter) )

secretion secretion (common, (common, via via Na+/K+-Na+/K+-ATPaseATPase, , increased increased by by aldosteronealdosterone), ), or or reabsorptioreabsorption (rare, n (rare, hydrogen pohydrogen potassium tassium ATPaseATPase

CalciumCalcium Uses Uses calcium calcium ATPaseATPase, , sodium-calcisodium-calcium exchangum exchangerer

reabsorptioreabsorption n

reabsorptioreabsorption (thick n (thick ascending) ascending) via via passive transpassive transportport

MagnesiumMagnesium Calcium Calcium and and magnesium magnesium compete, compete, and an and an excess of excess of one can one can lead to lead to excretion of excretion of the other. the other.

reabsorptioreabsorption n

reabsorptioreabsorption (thick n (thick ascending) ascending)

reabsorptioreabsorption n

PhosphatePhosphate Excreted as Excreted as titratabletitratable acid acid

reabsorptioreabsorption (85%) via n (85%) via sodium/phossodium/phosphate phate cotransportecotransporterr Inhibited Inhibited by by parathyroid parathyroid hormonehormone

Acid base homeostasisAcid base homeostasis::

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

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

Water homeostasisWater homeostasis::

Water homeostasis is determined by :Water homeostasis is determined by :

water intakewater intake

extrarenal water loss.extrarenal water loss.

Solute loadSolute load

Kidney ability to produce concentrated or Kidney ability to produce concentrated or

diluted urinediluted urine

The minimum urine volume is determined by The minimum urine volume is determined by

solute load to be excreted and may be as low solute load to be excreted and may be as low

as 400 ml/ d.as 400 ml/ d.

The maximum urine volume is determined by The maximum urine volume is determined by

water load to be excreted and may be as mnch water load to be excreted and may be as mnch

as 20-25 L/ d.as 20-25 L/ d.

Osmolal clearance ( C osm) represent Osmolal clearance ( C osm) represent

volume of urine that would be required volume of urine that would be required

for isoosmolal clearance of solute load.for isoosmolal clearance of solute load.

Free water clearanceFree water clearanceNegative free water Negative free water clearanceclearance

Difference between actual Difference between actual urine flow rate and flow urine flow rate and flow rate calculated for rate calculated for isosmotic excretion .isosmotic excretion .Measure diluting abilityMeasure diluting abilityIn excess that required for In excess that required for isoosmolal urineisoosmolal urineC H2O= V-C osmoC H2O= V-C osmo

Measure concentrating Measure concentrating abilityabilityWater reabsorbed from Water reabsorbed from tubular fluid during tubular fluid during production of concetrated production of concetrated hypertonic urinehypertonic urineC H2O= C osmo - V C H2O= C osmo - V

Two main process are involved in in water Two main process are involved in in water reabsorptionreabsorption

Isosmotic reabsorption of water from PCT:Isosmotic reabsorption of water from PCT:

About 80% returned to the body by PCTAbout 80% returned to the body by PCT

Active solute reabsorption from the filterate is Active solute reabsorption from the filterate is accompanied by passive reabsorption of an accompanied by passive reabsorption of an osmotically equivelant amount of waterosmotically equivelant amount of water

Differential reabsorption of water and solute Differential reabsorption of water and solute from the loop of Henle, DCT, CD: two from the loop of Henle, DCT, CD: two mechanism are involvedmechanism are involved

Countercurrent multiplicationCountercurrent multiplicationCountercurrent Countercurrent exchangeexchange

Active processActive process

In loop of HenleIn loop of Henle

In absence of ADHIn absence of ADH

Lead to production of diluted urine Lead to production of diluted urine

(low osmolarity) and increase (low osmolarity) and increase

plasma osmolality.( in loop of Henle plasma osmolality.( in loop of Henle

reab of Na & Cl without water).reab of Na & Cl without water).

Passive processPassive process

In DCT and CDIn DCT and CD

In presence of ADHIn presence of ADH

In abscence of ADH the In abscence of ADH the

collecting duct impermeable collecting duct impermeable

to waterto water

Produce conc.urine and Produce conc.urine and

plasma is dilutedplasma is diluted

Endocrine function:Endocrine function:

HormonesHormones producedproduced by the by the kidnekidne

Renine – erythropoietin- Renine – erythropoietin- prostaglandins- kinin-vit D- prostaglandins- kinin-vit D- natriuretic peptidesnatriuretic peptides

Hormones thatHormones that controlcontrol kidney functionkidney function

Aldosterone- PTH- ADH- Aldosterone- PTH- ADH- calcitonin- natriuretic H- calcitonin- natriuretic H- thyroid H- glucocorticoid- thyroid H- glucocorticoid- somatomedinsomatomedin..

HormonesHormones catabolised catabolised by the by the kidneykidney

PTH- calcitonin- insulin- PTH- calcitonin- insulin- somatomedin- GIT hormones- somatomedin- GIT hormones- vasopressin- hypothamic RH- vasopressin- hypothamic RH- prolactin- angiotensin II.prolactin- angiotensin II.

AldosteroneAldosterone

Aldosterone is a Aldosterone is a steroid hormonesteroid hormone ( (mineralocorticoidmineralocorticoid family) produced by the outer-section ( family) produced by the outer-section (zona glomerulosazona glomerulosa) of the ) of the adrenal cortexadrenal cortex in the in the adrenal glandadrenal gland, and acts on the , and acts on the distal tubulesdistal tubules and and collecting ductscollecting ducts of the of the kidneykidney to cause the conservation to cause the conservation of of sodiumsodium, secretion of , secretion of potassiumpotassium, increased water , increased water retention, and increased retention, and increased blood pressureblood pressure. Aldosterone is . Aldosterone is part of the part of the renin-angiotensin systemrenin-angiotensin system..

Its activity is reduced in Its activity is reduced in Addison's diseaseAddison's disease and increased and increased in in Conn syndromeConn syndrome..

vasopressinvasopressin

Arginine vasopressinArginine vasopressin ( (AVPAVP), also known as ), also known as vasopressinvasopressin, , argipressinargipressin or or antidiuretic antidiuretic hormonehormone ( (ADHADH), is a ), is a hormonehormone found in most found in most mammalsmammals, including humans., including humans.[1][1] Vasopressin Vasopressin is a is a peptide hormonepeptide hormone. It is derived from a . It is derived from a preprohormonepreprohormone precursor that is synthesized in precursor that is synthesized in the hypothalamus and stored in vesicles at the the hypothalamus and stored in vesicles at the posterior pituitary. posterior pituitary.

vasopressinvasopressin

Arginine vasopressinArginine vasopressin ( (AVPAVP), also known as ), also known as vasopressinvasopressin, , argipressinargipressin or or antidiuretic antidiuretic hormonehormone ( (ADHADH), is a ), is a hormonehormone found in most found in most mammalsmammals, including humans., including humans.[1][1] Vasopressin Vasopressin is a is a peptide hormonepeptide hormone. It is derived from a . It is derived from a preprohormonepreprohormone precursor that is synthesized in precursor that is synthesized in the hypothalamus and stored in vesicles at the the hypothalamus and stored in vesicles at the posterior pituitary. posterior pituitary.

One of the most important roles of AVP is to One of the most important roles of AVP is to

regulate the body's retention of water; it is regulate the body's retention of water; it is

released when the body is dehydrated and released when the body is dehydrated and

causes the causes the kidneyskidneys to conserve water, thus to conserve water, thus

concentrating the concentrating the urineurine, and reducing urine , and reducing urine

volume. In high concentrations, it also volume. In high concentrations, it also

raises blood pressure by inducing moderate raises blood pressure by inducing moderate

vasoconstrictionvasoconstriction. .

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

Erythropoietin or EPOErythropoietin or EPO

Is a Is a glycoproteinglycoprotein hormonehormone that controls that controls erythropoiesiserythropoiesis, or red blood cell production. It is , or red blood cell production. It is a a cytokinecytokine for for erythrocyteerythrocyte ( (red blood cellred blood cell) ) precursors in the precursors in the bone marrowbone marrow. It is produced by . It is produced by the the kidneykidney, and is the , and is the hormonehormone that regulates that regulates red blood cellred blood cell production. It also has other known production. It also has other known biological functions. For example, erythropoietin biological functions. For example, erythropoietin plays an important role in the brain's response to plays an important role in the brain's response to neuronal injury. EPO is also involved in the neuronal injury. EPO is also involved in the wound healing process. wound healing process.

An intermediate is created by An intermediate is created by phospholipase-A2phospholipase-A2, , then passed into one of either the then passed into one of either the cyclooxygenase pathwaycyclooxygenase pathway or the or the lipoxygenase pathwaylipoxygenase pathway to form either to form either prostaglandin and thromboxane or prostaglandin and thromboxane or leukotrieneleukotriene. . The cyclooxygenase pathway produces The cyclooxygenase pathway produces thromboxanethromboxane, , prostacyclinprostacyclin and prostaglandin and prostaglandin D, E and F. The lipoxygenase pathway is D, E and F. The lipoxygenase pathway is active in active in leukocytesleukocytes and in and in macrophagesmacrophages and and synthesizes leukotrienes.synthesizes leukotrienes.

TypesTypes

Following is a comparison of the prostaglandin Following is a comparison of the prostaglandin

types types Prostaglandin I2Prostaglandin I2 (PGI2), (PGI2), Prostaglandin E2Prostaglandin E2

(PGE2) and (PGE2) and Prostaglandin F2αProstaglandin F2α (PGF2α). (PGF2α).

Type Type ReceptorReceptor Function Function

PGI2PGI2

IP IP vasodilationvasodilation inhibit inhibit platelet aggregationplatelet aggregation bronchodilatationbronchodilatation

PGE2PGE2

EP1EP1bronchoconstrictionbronchoconstriction GI tractGI tract smooth musclesmooth muscle contraction contraction

EP2EP2bronchodilatationbronchodilatation GI tractGI tract smooth musclesmooth muscle relaxation relaxation vasodilatationvasodilatation

EP3EP3↓ ↓ gastricgastric acid secretion acid secretion ↑ ↑ gastricgastric mucusmucus secretion secretion uterusuterus contraction (when pregnant) contraction (when pregnant) GI tractGI tract smooth musclesmooth muscle contraction contraction lipolysislipolysis inhibition inhibition

↑ ↑ autonomicautonomic neurotransmittersneurotransmitters [6][6]

Unspecified Unspecified hyperalgesiahyperalgesia[6][6] pyrogenicpyrogenic

PGF2αPGF2α FP FP uterusuterus contraction contraction bronchoconstrictionbronchoconstriction

Vitamin DVitamin D

Vitamin D3 has several forms:Vitamin D3 has several forms: Cholecalciferol, (which is an inactive, unCholecalciferol, (which is an inactive, un

hydroxylatedhydroxylated form of vitamin D3) form of vitamin D3) Calcidiol (also called 25-hydroxyvitamin D3), Calcidiol (also called 25-hydroxyvitamin D3),

which is the form measured in the blood to which is the form measured in the blood to assess vitamin D status assess vitamin D status

Calcitriol (also called 1,25-dihydroxyvitamin Calcitriol (also called 1,25-dihydroxyvitamin D3), which is the active form of D3. D3), which is the active form of D3.

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

MetabolismMetabolism

7-Dehydrocholesterol is the precursor of vitamin 7-Dehydrocholesterol is the precursor of vitamin D3 and forms cholecalciferol only after being D3 and forms cholecalciferol only after being exposed to solar UV radiation.exposed to solar UV radiation.

Cholecalciferol is then hydroxylated in the liver Cholecalciferol is then hydroxylated in the liver to become calcidiol (25-hydroxyvitamin D3).to become calcidiol (25-hydroxyvitamin D3).

Next, calcidiol is again hydroxylated, this time in Next, calcidiol is again hydroxylated, this time in the kidney, and becomes calcitriol (1,25-the kidney, and becomes calcitriol (1,25-dihydroxyvitamin D3). Calcitriol is the most dihydroxyvitamin D3). Calcitriol is the most active hormone form of vitamin D3.active hormone form of vitamin D3.

Laboratory testsLaboratory tests::Glomerular function tests:Glomerular function tests:

clearanceclearance

Creatinine clearance test. Creatinine clearance test. This test evaluates how efficiently the kidneys clear a This test evaluates how efficiently the kidneys clear a

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

Calculation of CCalculation of CCrCr

The urinary flow rate is still calculated per minute, The urinary flow rate is still calculated per minute, hence hence

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