maintained, some waste products ha ternal nnvironment > “Homeostasis is the maintenance of consta ” ofthe various body fluid compartments has to be tt0 be removed from the Plasma portic portion of b of blood, volume ¢ of t the haas to be regulated, the water concentration an and cleoirolyte composition of the body * fluids have to regulated etc, sc, The kidney isa major (r (not the only).organ that participates homéostasis._ - ‘ Pre lus @ | “,Runotions of the Kidney yr Pw oO Sughe kidney performs the following functions: S S* PTE A NSc (@) Regnlation of water and inorganic ~ ion balance., from the blood and their excretion in the. (b) Removal of metabolic waste products urine (c) Removal of foreign cl (¢) Gluconeogentesis- The kidney synthesizes glucose from amtino acids a precursors during prolonged fasting. (@) the kidney secretes exythropoietin, renin, 1, 25- dihydroxyvitamin Dy ( (faa Ainge (© Regulation of arterial blood pressure ase balance: e Kidney (26 TDPRI TONY Jhemicals from the blood and their excretion in the urine (elo home” nd other (g) Regulation of acid Structural Organization of th cavity. Egch kidney in a healthy man weighé 6150 gm to region of the posterior abdominal c ‘The weight of the two Kidneys is about (oe the kidney is about 25% of the cardiac output of 1,250 ml/min at rest. © The Nephron ghey ducal $uncbional vo of ata een idney. Each nephron is made up This is the basic unit of structure and function of the kidney. tial corpuscle and (1) An initial filtering component called renal \ (2) tubule that extends out from the renal nal corpuscle. Parts of Nephron connected capillary loops called the, glomorulus ‘The renal corpuscle is composed of interes A taries arise from | Glomerular capillaries) and the Bowmant’s ari "an afferent Lae. tI ss | - NS capsule. Glomerular capil ¢ reunite to form the cl t arteriole; all the smaller capillarieseS arteriole. The glomertijar capillary a capsule 1 like * whose diameter is less than of the i nan’s * endothelium has pores with @ di + filtration. Bows meter of 0.1 # fo! odocytes, that have Sfingel S envelopes the glomerulus, it is made up of cells called p+ : men bers % projections used for flitratton. These layers are separnted by basal tari ioe ae ve Sugh to allow ® membrane), ‘The spaces in the basement membrane are mot large enous ‘ iltration of plasma proteins. In addition, the strong negative clectifgal charges associated with the proteoglycan component of the basement membrane pel proteins, + their bei “vis, the basement membrane ‘rovides the : major restriction to plasma proteins getting into the glomerular filtrate. This filfrate then leaves the renal corpuscle and enters the tubule. As it flows through the tubules, i substances are added to itor removed from it, Ultimately the fluid from all the nephrons fuidfroiee “es cite \y ‘The renal tubule is made up of: : ‘The proximal convoluted tubule 2, Loop of Henle which is made up of: a. The thick descending limb further preventing their being filtered. é leaves the kidney. 1S AS b. The thin descending. limb c. Hairpin bend d. Thin ascending limb e. Thick ascending limb Piotr woreted) 3. The distal convoluted tubule WASDPRESSIN 70 OM agi w The distal convoluted tubule coalesces lo forni collecting duets. The collecting duct is 1 et ed by'cuboidal epithelium of two types: Principal (P) cells and Inteicalated (cells. I are more numerous, they a involved in Nat reabsorption and water cretion 4 Lian under Ihe influence of vasopressin. I cells are involved with acid ser and HCOs There are actually 2 types of nephrons _ nephrons and the juxtamedullary nephrons. with some differences, We ‘have: the cortical |, Types of Nephron : _ Cortical nephrons ca eet us + Bowmun’s capsule) it sa Natal sent al * thoy have their renal corpusele fenle and repre! ey have short loop of Henle hence the name ‘Corticalihe nephrons in humans. Their tubule is supplied by a network of capil een ork of capillaries called il = Giomer apillaries are connec! he peritubular capillar oa fever ular capillaries connected to the peritubul: ries in effer atteriole, after supplying the tubules with blood, the peritubula ‘coalesce { le peritubulai sce to : ilar form the veins by which blood leaves the kidney. This is a uinique feature of, renal €irculation. OG : a Juxtamedullary nephrons These have their corpuscles in the inner cortex, are supplied by straight capillari have long loops and représent about called 45% of nephrons in humans, Their tubules yasa recta which run parallel to the tubules. which is a high-pressure vessel, this 1. Renal arleries arise from thes high-pressure blood flow'to the kidney. ensures a! 1900 mil of blood per mitiyte. To put simply, 2, Both kidneys receive about 120% 20-25% of the cardiac oulpul out Be Pita passing througlt the kidney passes through glomerular capillaries i where itis completely filtered. oe : i 4, Renal ciroulation has {we, networks. of capillaries i.¢ glomeriilar™ an peritubular capillaries. ss poll 8 weer ny ce ques eon enkor pet #2 eezz . bed of about 60-70 nut . Glomerular capillaries form a high-pressure r ‘than That-of efferent because the diameter of afferent arterioles 1s greater . arteriole, Compare with other systemic capillaries which a about 25-80 mm Hg, This high pressure i needed in the kidniey beau a pressure Of cause it helps in glomerwlar filtration, s capillaries 5 6. Unlike glomerular capillaries with high pressure, peritubu to be to facilitate about 8-10 mm Hg. This has t tubule reabsorption, remember peritubular capillaries surround | When substances are reabsorbed from the tubules, they are reabsorbed i form a bow-pressuure bed of he tubules nto the peritubular capillaries and finally into the veins. High pressure will nol : favour thal. Renal blood flew is autoregulated. Urine Formation Ihe pr cess of urine formation begins with the filtration of plasma at the glomerulus | ‘The process is culled glomerular filtration and the filtrate is called glomerular filtrate or are filtered. The filtrate is very similar to ujirafiltrate because even very small particles of their large 2 plasma except it has no plasma proteins which are not filtered becaus size 1 Abecuit, ¢ they are negatively charged and so they are repelled by the negatively clvie: (fill: ation channels. However, sme low-moleculir weight proteins are filtered \ihile omg low-molecular weight substances are not filtered at all or ave partially aleium cause they are bound to plasma proteins, For instance, half the plasma fivered » gad ai/ ost all the ph Jasma fally acids are nol fillered because they are bound to plasma oh yams Ihe filtrate then pases through the tubules, During its passage, some wanted substances imino acids, “yater’and blectrolyles are absorbed into jou. On the other hand, some substances are rele tubular capillary. d this is known as tubular. secretion or /iikelghucost nis is called wbular gapillaries Intothe tubule, " 2 [from peritubular : excretion. ‘wherefore, : 1, Glomerular fillration * ' the process of urine formation involves: 2, Tubular reabsorption * ‘Tubular secretion * aby.Afferent 3 arteriole Filtration 4 Peritubular. “capivary- Tubular portion —— F Venous blood Urine Events of Urine Formation {Glomerular filtration driven event, it is determined by the net direction of "Glomerular filtration is « pressure es that favour filtration and forces that oppose filtration. forces between fore | Forces that favour filtration “this is the glomerular capillary pressure of about 60 mintig ( {some GD Dern. 1. Forces that oppose filtration i" ‘These are: a. Osmotic force of plasma proteins in the glomerulus, this is. about 2! 9mm lig e Bowman’s space, this is about 15. mms. b, ‘The hydrostatic pressure in th Now the net fillration pressure = 60 ~ (26415) = 20 mm HE, Normally, thisis positive because the glomerular capillary hydetatic pressure isalways atic pressure in Bowman *s space and the osmotic greater than the sum of the hydrost force opposing filtrationGlomerular filtration rate (GFR) This is the volume of fluid filtered froin the glomeruli into Bowman’s space per. tit tinge. It is about 125 ml Per minute of 180L/day. The total volume of, plasma is about value 31; therefore, the entire plasma is fillered about 60 times a day. GFR is nol a fixed but is subject to physiological regulation. Filtration fraction This is the fraction of the renal plasma Ge. plasma being fillered by the. glomerulus) na flow and glomerular the fillrate; il is the ratio between renal flas which becom Filta. f ‘ Filtration fraction = GFR X 100 : : Renal plasma flow 4 = 125ml/min X 100 650ml/min F = 19.2% Filjered load ‘Tlie fitered load of.a substance is the GFR multiplied by the plisma concentration of tha substance. 11 is a way of measuring:tho amount of the substance filtered into Bowinan’s ss Ris 18 Space. For instance, glucose GFR is 180L/day and plasma glucose concentration is 1/1, 805/day) is the filtered load of glucose. Once we kifow the veted then 180L/day X 1g/L (= fillered load of a substance we can compare it to the amount of the substance aiid tell whelher the subslance has undergone net tubular absorption or nel seeretion. Fitors regulating (affecting) GFR Tubuloglomerular feedback mechanism ‘Tubuloglomerular feedback is the influence of feedback signals from the renal tubules Jomerular filtration. As the rate of flow through the ascending limb of Henle’s loop ons! aid ain 0Noases, glomerular filtration in the same nephrog decreases. Macula je concentration and alters the GFR by vasoconstricting” NGhior Fthe sodium 1 chloride “concentration is high, there alensa aR Rithe sodiul or Pasodiatin, rioles. "ifthe reduces the GFR, if it is low, there is an afferent jolar constriction that. is‘afferent ar es the GFR. anteriolar dilation that now increas fe- Glomerular balance Jncrease in Causes an increase i Ai ¢ in GFR causes an i he reabsorption of solutes, and cor of water, primarily i the proximal tul ibule, so'that in general the percentage of the solute reabsorbed is held const i : ant. This process is $iomerulotubular balarice”. paitioularly Prominent for Na+. (Thue’s ealareo othe, Glomerular capillary pressure W774 Wve and is BOSS he higher the glomerular capillary pressure, the higher the SRR vice versa. Colloidal osmotic pressure Thie colloidal osmotic pressure is one ofthe forces that oppose filtration. Therefore, the higher colloidal osmotic pressure exerted by the proteins, the lower the GFR. Bawman’s space hydrostatic pressure Tiie higher the hydrostatic pressure in Bowman’s space, the lower the GFR. \ Renal blood flow — This is the most necessary factor for GFK ‘The higher the renal blood flow, the, higher the GFR and vi vice versa. ‘Afferent arteriolar constriction or dilation 1 of the afferent arteriole reditces blood flow to the glomerulus and this reduces GER. Dilation does the opposite. oe . f “ ~ Systemic arterial pressure Tho ambired ingedny micraaview Ft beken Gbminlkg Increase or decrease of mean arterial pressure (MAP) beyond 180 mm Hig or below 60 Cénstriction vim Hg respeclively has a corresponding effect on GFR. This is because autoregulatory mechanism fails in this range Sympathetic stimulation Mild sympathetic stimulation does not Shrong sympathetic stimulation causes al ent arleriole, The GFR is initially increased but is decre itect GFR because of autoregulatory mechanism. vent and effer ent arteriolar constriction with d more effect on the ef subsequently. Surface area of capillary membrane , the higher the GFR, vice vers The higher the surface area of capillary memb Permeability of capillary membrane al states peability The higher the permeability, the higher the Gk, vice versa. P thophysiologic: he peri Uke hypoxia, lack of blood supply, or presence of « toxin can imerease the Pe 2 thal even plasma proteins are filtered and excreted in ur ine. ——rt‘Tubular reabsorption ‘Thigis the second stage in urine formation, whereb! inté: the peritubular capillaries. This process var! ie nces are red bsorbed y needed substa .s for different sul reabsorbed while 0! pstances based on their pstances, Some thers are substances are completely reabsorbed, some are partially nol:reabsorbed at all. Therefore, there are three ¢! asses of su degtee of reabsorption thus: CD High threshold substances ‘Tiiese are completely reabso when their plasma concentration is very bed, and so do not normally appear in the urine excep! high and in renal diseases. B xamples ‘are gftcose, aunino acids, vitamins. @ Law threshold substances ‘These substances are partially reabsorbed so they appear in urine even under normal ne a e urea, uric acid and phosphate conditions, Examples a (@xion ~ threshold substances GaAlynine = vade pdxay of muscles mebets "These are not absorbed at all and are therefore freely excreted in, the urine. mples age creatinine. Substances that are veabsorbed are actually transported by a particular igansport mechanism (Diflusion, active transport etc.). It therefore goes without saying, ihat the extent of reabsoxplion of a substance depends on the transport amechanism it amploys. Many renal transport systems, like other transport systems, have amaximum fate at which a substance is transported and thus reabsorbed, this maximum value is For glucose if is about 375 mg/minute in men and n, If this Tm is exceeded, glucose is nol completely reabsorbed known as transpo imum 800 mg/minute in wo -s0 i appears in urine (glycosuria). This isthe ease in diabetes mellitus. “It is not only at the level of renal tubule that we have a critical value for substances to {be reabsorbed, it is also present in.the plasma or blood. That means there is a level a © substance must not exceed in blood if it is to totally reabsorbed, if this level is exceeded, lathe subslance is still filtered but is not completely reabsorbed. That level in plasma is “called renal threshold for that substance. For example, renal threshold for ghicose is 180 enal threshold for that ; mg%, glucose is completely reabsorbed from tubular fluid if its level in plasmna or blood is not beyond 180 mg%, if this level is exceeded in plasma, ghicose is not completely reabsorbed from tubular fluid so it appears in urine. ) Mechanisms and sites of tubular reabsorption ‘Tubular reabsorption takes place in almost all the segments of a nephron and tlie pro can be active or passive. @ srular fillvate is a continuous process, each lime the isotonic 7 Since the formation of glont fluid entering the U-shaped portion of the nephron leaves this portion, itis hypotonic ntinuous deposition of NaCl “because of loss of NaCl info the:renal interstitium, This inthe renal interstitium isa called a mtultiplier effect. This leads to accumulation of NaCl yin the renal interstitium. 5 Urea, a waste amino acid’ metabolism also contributes to the osmolarity of the renal m/1) of the interstitium, mdeed, ureéi contributes about 40% of the osmolarity (800 most Nal and or Bisbal quince eo. (OD - © Waker Aten ny are Yeatnestocd Ue, % 20 mogm|L mov re Yer) water ebibivwyspe eval mesallary Hoterstitiam when the “kids holming bh maxiradlly bones “rine. Urea is passively reabsorbed from the: Hngltubutes, bpt this passive reabsorption > proximal tubule and the janer partion of the medullary’ collecting duct. Apart from the proximal convoluted wij (POM and the inner portion of the ‘colle ihe tu ath ‘passively ‘out of the proximal tubule and baggaero, the inipériieability of iteploop of iMente ane DCT fo urea, urea is increasingly cjpoen ed inthe tubular fluid ajwater moved in the loop and distal tubule. Héwever, When the tubular fluid reaches the ‘occurs only in ff duet, the tmeable, to urea, a, Thus; urge moves w lis ‘innerfnedullary portion of the collecting duct, trea diffuses. passively into thé: | “iinterglium of the pyramids, adding to its hyperosmolarity. Coustigreurrent Exchangers ‘The 4) racla also have U-shaped configuration like the U-shaped portion of the mnepliyon. blood flow in the vasit rela is also of the countercurrent pattern. Vasa recta runs parallel to loop of Henle, Its descending limb runs along the ascending limb of Henle idop and its As blood in the v ns along wilh scending limb of Henle loop. recla flows from the corlico-medullary junétion into the deeper Inyers of the medulla, the blood traverse areas of increasing osmotic. cohcentration. Since the vasa recta consist of loops of capillaries, its wall freely: permeable to water and electrolytes. Thus, as blood in the vasa recta moves i to the deeper layers of the medulla, ils contents equi ‘condtintrated. By the time the blood in the vasa recta reaches'the level of the papilla, its osmotic concentration is 1,200 milliosmoles. The vasa recta then curve.round the loop je of Henle nd blood flowing through it moves from the papilla tegion back to the cortico- medullary junction. As it does this, {he blood passes through areas of decreasing osmotic [concentration. Mast of the solutes gained by the blood on entry into the medulla is lost / ‘into the interstitium on exil. However, all the solute gained by the vasa recta is not given : ‘up on exit from the medulla. A very small quantity of soluie- is removed. The asa recta, by giving up the electrolylcs il gained on entry as it moves out of the dulla, is said to act as countercurrent exchangers, This process prevents the blood _flovy fo this part of the kidney from carrying away the high solute concentration that the coifMiei current mullipliors have buill up in the renal interstitial tissues. By giving up on Ari the solutes it gained on entry, the vasa recta help to preserve the osmotic “eongeattestion gradient carlicr established by the U-shaped nephrons. The other imp whant role of the vasa recta is that by removing on exit a very: small quantity of the: . sfincotatte ta the-renai ineasimun, i eset ; Se * fala Solutes in the interstitin : i Role of Antidiuretic heeinione When Synoltrity of tfeibody Nuids increas ove normal (that is, the solutes in the “body Nelte Necome too.rongentrated), the posterior piluilary gland secfetes ni re ADM, _nnich mgeesises the perineal, of the asta aba sand collecting ducts ro water. this ter lo be reabsorbed and decreases utite voluime but cloee “allows large amounts of Water to be res Nol markedly alter the rate of renal excretion of the solutes, fluid osmolarity is reduced, , thereby reducing. the which eauses large When there is excess waler in the body and extracellular the seeretion,of ADH by ithe posterior pituitary decreases, of the distal fubute and eolicciing ducts io water, “permeat 0 amounts of dilute urine lo be excreted. Thus, the presence of absence of. ADH 2 fermines, lo a latge'extent, whether the kidney excretes dilute or a congentrated determines: : ‘urine. ‘Micturition : the urinary bladder, that is, th process of urination. femplyin; gictrirition is process ob ent yi on: volved in micturitio oe Dita uni the pressure rises to a critical Value, + bladder, Rese Hig Sa snjcuriton reflex which empties the bladder. : called the ex calle 4 neuronal refl Gi @ 74 graph of the intravesical prebssure against the volume of urine inside the bladkic called a cystrometrogram wing also acute pressure waves (dashed spikes) caused by Normal cystometrogram, sho | : micturition reflexes. Wher there is no urine in the bladder, the pressure in the bladder js almost zero. As urinelaccumulstes in the bladder, bladder pressure rises. When volume of urine in se bladder is about 100m, intravesical pressure is between 5 and 10,cm of water. 4s the volume of urine increases up to about 300 to 400ml, there is only a small and gradual rie in intravesical pressure. As bladder volume increases beyond 400ml, there is a'sharp ical pressure. As the blaclder is distended with increasing volume of icturition Waves in the itcrease in intray ufine, intermittent waves of pressure rise occur. ‘These are eysiomeiroyram and this is caused by the micturition reflex. Micturition Reflex AS Ae atin becomes distended with urine, the stretch receptors’ in its walls are ted and [his gives rise fo a wave of contraction of the detrusor muscles. This leads to the spinal cord. If the person is not stimijl 5 nge lo micturale. Afferent impulses tr (othe urge lo micturale, Afferent ft one a a to volt yet, inhibilory impulses are sent from the verebral cortex so that there is reaa vo ye a Tea pads to ge and reduced parasympathetic discharge. This Je and contraction of the internal urethral sphintelgr and in the bladder wid the inoreased sympathetic relaxation of the detrusor muse! the uige to void off. More urine continues to accumulate micturition reflex is repeated. When the volume of urine in the bl the intravesical pressure starts to rise steeply. This gives rise lo frequent and. intense | desire to void. At this point, it is not easy to suppress the urge for too long, Witen the i individual is ready to'void, there are facilitatory impulses from the higher centers leading to inci eased parasympathetic discharge and reduced sympathetic discharge. The | diaphragm ¢. escends and { respiration is arrested in the inspiratory phase. The abdontinal tee muscles contract and the external sphincter relaxes. The increased pressure due to} a, rt contractioi: of.the detrusor muscles, the increased intra-abdominal pressure due lo. ¢ ion of! ladder is above 4001, shragmatic descent and contraction of le abdominal muscles and the rela +. val and external uréthral sphincters leads to emptying of the bladder: Diures. Diuresis is the , »>2% age of a large volume of urine. There are two types of diuresis: Fluid dfure.i. tssmetimes called water diuresis) Fluid jada dunce mM "2) Osmotic diures.. ‘v. solute diuresis) Oxooboe| eSvhe Acris Ruid Diuresis ‘This is due to ingestion of large «, eon, "he excess fluid is absorbed int iye vlood. volun : and a reduction 6f the plasma ton{oti. ‘The increased blood \ olume leads to ‘ity of { uid. This can be’ vater, soft drinks, tea or sis Jeads to jin increase in blood! increase ‘W cardiac output and therefore increase im glomerular filtration rate, The diurtic hormone (ADI reduced puicma tonicity causes 2 reduction or cessation of a result of this, the walls of Ue distal convotuted tubule and, Water. ‘This leads fo a Jos: ~f.Jot 01 water leading to water release into "ne blood. As 4 ollecting duct eve imperimeable to ic Lene, hence the diuresis. Tea, apart from us hish production of hypetou! ontains theobrowr ine which causes dilatation of the renat ble ad ye: sels eacling renal bloo-t/Tow. So, the diuretic effect of the tea is not just asa esl . se, etalon plasma whiel inl na Nedle al jaload flo content, C0} Ke of a large quantity of Wea can ¢ yw and therefore increased glomert water content but also, fo an increase i slay filealion of hypotonicily of ren " y because of its larg pecause:of its effect 0 ih siaresis 18 7 ‘ a 50 causes dite ADH release, Hence the oom bined a a ol content: Aleoliol suBereseS hibitory effect of alcohol , ¢ of its alcohol £0 ; or beer and the inhibitory ef i becaus ates ed toni nicity.of “effects of hyper” a 4on pl release makes beer to produce a greater diuresis than an equal volume’ of ‘will produce, Aes 3 “sollte Diuresis ym 'S sometimes called osmotic diuresis. It is due to the presence of unabsorbed : wee bia ‘molecules in the tubular Iumen. Excess sodium, glucose oF UFE ne c ome re osmotically active. Since the excess cannot be reabsorbed, they draw ht Hetiives 80 that the excess solute and the retained water is excreted leading ioe 'arge volume of urine, This is the basis of the polyuria in diabetes mellitus. _ Mannitol isalso an osmotic sohite) diuretic. ILis not reabsorbed from the tubular lumen one itis filtered; hence mannitol infusion causes osmotic diuresis. ‘The latter is the basis ~ alte ise of mannitol infu: * caluse diuresis. They are knot n in clinical medicine to reduce oedema. Certain drugs mas diuretics. An example is furosemide. » Characteristics of Urine ;» The characteristics of urine include the physical and chemical aspects that are often evaluated as part of a urinalysis lor 4 ) Amount—normal urinary output per 24 hours Is I to 2. liters. Many factors can significantly ch&inge output. Excessive Sweating or loss of fluid through diarrhea will decrease urinary output (oliguria) to conserve body water. Excessive fluid intake will crease urinary t (polyuria). Consumption of alcohol will. also increase output iuise alcohol inhibits the secretion of ADH, and the kidneys will reabsorb less water. Color—the typical yellow color of urine (from urochrome, a breakdown product of bile) is offen referred to as “straw” or “amber.” Concentrated urine is a deeper yellow (amber) {han is dilute urine. Freshly voided urine is also clear rather than cloudy. Specific gravity—the normal range is 1.010 to 1.025; this is a measure of the dissolved naterials in urine. The Specific gravity of distilled water is 1.000, meaning that there re no solutes present, Therefore, the higher ie specific gravity number, the more ue dissolved material is present. Someone who has been exercising strenuously and has lost "body water in sweat will usually produice less urine, which will be more: concentrated land have a higher specific gravity. The specific gravity of the urine'is an indicator of the i ting ability of the kidneys: ‘The kidneys must excrete the waste products that aintly formed in as little water as possible 5% water, whick_is ‘the solvent for waste oT Foducts because they may well | . | Constituents—urine is approximately 9: will Be excreted in urine | products and_salts. Salts are not considered true waste p! ' be utilized by the body when needed, but excess amounts Pes wastes —as their name indic oy liver cells when exce ainine Comes from the metabolism of creatin Uric acid comes from the DNA and RNA. Although these are waste products, there is always a t of cach in the blood, Other non-mtrogeno! seid products inciide ! nts of urobilin from the hemoglobin of old RBC pH range of urine is between ¢ of 6.0. Diet nfluence on urine pif ore ne high-protein dict will resu