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Block VIII Module 1 February 25, 2010 Dr. A. Villaflor Group 2

THE KIDNEY - Regulate the composition and volume of the plasma water. - Determines the composition and volume of the extracellular fluid compartment. - Influence the intracellular fluid compartment by continuous exchange of water and solutes across all cell membranes. - Endocrine gland producing erythropoietin - Regulation of BP: Renin-AngiotensinAldosterone System (RAAS): regulates blood volume and amount of salt in the body Renal Blood supply - 21% of the cardiac output (1200 mL/min) - renal a --> interlobar a --> arcuate a --> interlobular (radial) a --> afferent arterioles --> glomerular capillaries --> efferent arterioles --> peritubular capillaries --> interlobular v --> arcuate v --> interlobar v --> renal v The Nephron - Functional unit - 1 million per kidney - Cannot regenerate - Physiologic loss of 10% per ten years after age 40 - The nephron 1. Glomerulus o tuft of capillaries o o o Lined by epithelial cells Enclosed by Bowman’s capsule Filtering structure


Filtered fluid is processed to form urine Proximal, descending limb, loop of Henle, ascending thin, ascending thick, macula densa, early distal, late distal, connecting tubule, cortical collecting, medullary collecting, large collecting ducts



Regional differences: o Cortical (peritubular capillaries surround the entire tubular system) o Juxtamedullary nephrons (vasa recta form the long efferent arterioles)

URINE FORMATION - Glomerular filtration - Tubular reabsorption - Tubular secretion Mathematical expression: Urinary excretion rate = filtration rate – reabsorption rate + secretion rate Glomerular filtration - Filtered fluid (glomerular filtrate is protein-free with no cellular elements) - GFR is about 20% f the renal plasma flow - Determined by balance of hydrostatic and colloid osmotic pressures, AND capillary filtration coefficient (Kf) (permeability and filtering surface area) Glomerular capillary membrane - Endothelium of the capillary - Basement membrane

2. Tubules o Several segments

and glucose are filtered well GFR = Kf X net filtration pressure Net filtration pressure = sum of hydrostatic and colloid osmotic forces that either favour or oppose filtration across the glomerular capillaries Kf = hydraulic conductivity and surface Forces Favoring Filtration .Increased filtration fraction 1.Decreased arterial blood pressure . Fraction of plasma filtered by glomerular capillaries (filtration fraction) Decreased glomerular hydrostatic pressure .RBF = renal artery pressure – renal vein pressure / total renal vascular resistance Renal artery pressure = systemic pressure Renal vein pressure = 3 to 4 mmHg Total renal vascular resistance = interlobar. Afferent arteriolar resistance 3.Size selective – bigger substances filters less o Water.Constriction of efferent arterioles (not less than 3-fold increase in resistance) Decreased GFR . afferent and efferent arterioles Filterability .Bowman’s capsule colloid osmotic pressure (OPb) Forces Opposing Filtration .21% of the cardiac output . Efferent arteriolar resistance Increased glomerular hydrostatic pressure .Increased glomerular capillary hydrostatic pressure HPg – determined by area of the glomerular capillaries (thickness of the membrane and the Renal - vascular resistance controlled by: Sympathetics Hormones Local internal renal control mechanisms . Na+. Increase GFR 2.Bowman’s capsule hydrostatic pressure (HPb) = 18 mmHg .Glomerular hydrostatic pressure (HPg) = 60 mmHg .1200 mL/ min .Increases arterial pressure .More that 3-fold increase in efferent arteriolar constriction or resistance Increased capillary colloid pressure . Arterial plasma colloid osmotic pressure 2.Charge selective – negative substances are filtered less o Albumin can’t pass through .Afferent arteriole constriction .Increased glomerular capillary filtration coefficient . Reduce renal plasma flow RENAL BLOOD FLOW (RBF) .Increased glomerular capillary colloid osmotic pressure 1.Dilatation of afferent arterioles .Glomerular capillary colloid osmotic pressure (OPg) = 32 mmHg Net filtration pressure = HPg – HPb – OPg + OPb = (60 – 18 – 32) mmHg = +10 mmHg GFR = Kf X (HPg – HPb – OPg + OPb) Increased GFR .Increased Bowman’s capsule hydrostatic pressure (obstruction to the urinary tract) .- Podocytes – foot-like processes (epithelial cell layer) have gaps called slit pores Primary point for restriction to plasma proteins is the basement membrane 1. Arterial pressure 2.

Maintain nutrient supply .Increase GFR 1.Decrease GFR 1.Maintain oxygen delivery . Prostaglandins Angiotensin – prevents drop in GFR AUTOREGULATION OF GFR AND RENAL BLOOD FLOW Intrinsic feedback mechanisms aimed to keep RBF and GFR in constant levels .Ensure relatively constant NaCl delivery to the distal tubules and helps prevent spurious fluctuation in renal excretion 1. Sympathetic activation 2. Afferent arteriolar dilatation – increase GFR 2. Norepinephrine/epinephrine 3.Allow precise control of renal excretion of water and solutes – prevent extreme changes in renal excretion Glomerulotubular balance .Arteriolar resistance Control Renal blood flow Net ultrafiltration pressure Increased afferent Decreased afferent Increased efferent Decreased efferent Physiologic control of GFR and RBF . Efferent arteriolar feedback mechanism .Uses the juxtaglomerular complex – macula densa cells (initial distal tubule) and the juxtaglomerular cells (walls of the afferent and efferent arterioles Drop in NaCl delivery to the distal tubule --Signal to the macula densa 1. Increase renin release from the juxtaglomerular cells – angiotensin cascade – increase GFR Myogenic Autoregulation of RBF and GFR . Afferent arteriolar feedback mechanism 2. Endothelin .Remove waste products of metabolism .Ability of individual blood vessels to resist stretching during increased arterial pressure High protein intake increases RBF and GFR High blood glucose increases RBF and GFR . Endothelial-derived nitric oxide 2.Tubules increase reabsorption rate in response in GFR Tubuloglomerular feedback .

9 180 4.320 180 4.318 0 2 Urine Excretory rate 25.560 25. H+) Glucose (g/day) Bicarbon ate (mEq/day ) Sodium (mEq/day ) Amount Filtered Amount reabsorb ed Amount Excreted % of Filtered load Reabsorb ed 100 >99.410 150 99.Physiologic and pharmacologic factors with effects on glomerular hemodynamics Afferent arteriolar resistance Renal sympathetic nerves Epinephrine Adenosine Cyclosporine NSAIDs Angiotensin II Efferent arteriolar resistance Renal blood flow Ultrafiltration pressure Kf GFR ? ? Endothelin-1 High protein diet Nitric Oxide Atrial natriuretric peptide (ANP) Prostaglandins E2/I2 Calcium channel blockers ACE inhibitor / angiotensin receptor blockers ? ? ? ? ? = glomerular filtration – tubular secretion + tubular reabsorption Glomerular filtrate flow Proximal tubule  loop of Henle  distal convoluted tubule  collecting tubules  collecting ducts  URINE Final urine composition Tubular reabsorption (most substances. urea. Na+) Tubular secretion (K+.4 . glucose.

Active transport o Primary o Secondary (co-transport.Transcellular .440 46.Quantitatively large o Small change in GFR and tubular reabsorption can potentially cause a large urinary excretion of that substance o Not true in reality. facilitated diffusion . for precise control of the composition of the body fluids Transport mechanisms .4 0 180 23.4 50 99. GFR and reabsorption is closely coordinated to prevent large fluctuations in urinary excretion .1 50 0 Tubular reabsorption .Chloride (mEq/day ) Urea (g/day) Creatinin e (g/day) 19.Highly selective o Tubular segments control the rate of reabsorption of each substance independently.Paracellular .Passive o Osmosis o Diffusion.8 1.8 19.260 23. counter transport) .Ultrafiltration (bulk-flow) – hydrostatic and colloid osmotic forces .

potassium. provides feedback control of GFR and blood flow .Thin ascending limb of the loop – less reabsorptive function . and chloride .Impermeable to water and urea .Intercalated cells o Secrete hydrogen and reabsorbed bicarbonate H2O + CO2  H2 CO3  HCO3 + H+ Absorbed secreted . simple diffusion occurs . moderately permeable to solutes.Principal cells o Sodium reabsorption and potassium secretion  K+ enters the cell because of the sodium-potassium ATPase  High intracellular K+ allows diffusion into the luminal fluid .Diluting segment Late distal tubule and cortical collecting tubule . highly reabsorptive function.Avid reabsorption of sodium.Thick ascending limb of the loop – high metabolic activity.Juxtaglomerular complex – first part of the distal tubule. impermeable to water Distal tubule .Descending part of the thin segment – highly permeable to water.Solute and water transport in the loop of Henle .

increase reabsorption rate 4.Final site for urine processing .Permeability to water is controlled by ADH . Glomerulotubular balance o Most basic controlling mechanism for tubular reabsorption o Intrinsic ability of the tubules to increase reabsorption rate in response to increased tubular load o Occur independently of hormones o Prevent overloading of the distal segments when GFR increases 2. increases plasma protein and thus increases capillary reabsorption rate 3. H2O reabsorption. Peritubular capillary and renal interstitial fluid physical forces o High arterial pressure increases peritubular o capillary hydrostatic pressure --. H2O reabsorption.Medullary collecting duct . K+ secretion  NaCl.Increases renin release and angiotensin II formation . Colloid osmotic pressure of the plasma o Systemic plasma colloid osmotic pressure increase peritubular capillary colloid osmotic pressure increases reabsorption o Higher filtration fraction means greater fraction of plasma filtered.  H+ secretion H2O reabsorption Angiotensin Proximal tubule Antidiuretic hormone Atrial natriuretic peptide Parathyroid hormone Distal tubule/ Collecting duct Distal tubule/ Collecting duct Proximal tubules. thick ascending loop of Henle/ Distal tubules NaCl reabsorption PO42reabsorption Ca++ reabsorption Sympathetic Nervous System .Secretes H+ against a large concentration gradient – role in acid-base regulation The relative degree of reabsorption of solute versus the reabsorption of water in a tubular segment.Activation increases sodium reabsorption in the proximal tubule.Permeable to urea . determines the concentration of that solute in the tubular fluid Regulation of tubular reabsorption 1. Renal interstitial hydrostatic and colloid osmotic pressure o Increase renal interstitial fluid hydrostatic pressure decreases interstitial fluid colloid osmotic pressure.decrease reabsorption rate High resistance of the afferent and efferent arterioles decreases capillary hydrostatic pressure --. GFR decreased .Activation constricts the afferent and efferent arterioles. decreases net reabsorption Hormone Aldosterone Site of Action Distal tubule/ Collecting duct Effects  NaCl. the ThAL .increase tubular reabsorption REGULATION OF ECF OSMOLARITY AND SODIUM CONCENTRATION Osmolarity .

Controlled by fluid intake o Regulated by factors that control thirst .Alters renal excretion of water independently of the rate of solute excretion . if ADH is absent. (hypoosmotic).Excess body water – urine osmolarity can reach to 50 mOsm/L (dilute) . High osmolarity of the renal medullary interstitium – provides the osmotic gradient needed for water reabsorption in the presence ofADH Medullary interstitium surrounding the collecting ducts are NORMALLY HYPEROSMOTIC The presence of ADH in high levels move water from the collecting tubules to the interstitium Water is reabsorbed back into the blood by the VASA NRECTA --.Secreted by the posterior pituitary gland .Descending limb of the loop of Henle – water reabsorbed by osmosis making the tubular fluid hypertonic (until it equilibrates with the surrounding interstitial fluid of the renal medulla) – about 4x the original glomerular filtrate osmolarity - Ascending limb of the loop of Henle – both the thin and the thick segments.Glomerular filtrate osmolarity is about the same as plasma (300 mOsm/L) . Osmolarity can be as low as 100 mOsm/L – 1/3 that of plasma.Vasopressin .minimal amounts of concentrated urine Creation of a hyperosmotic renal medullary interstitium .Results from the continuous reabsorption of solutes and failure of water reabsorption from the distal tubules . K+.Large amounts of dilute urine is excreted. until the early distal convoluted tubule Hypoosmolarity of the fluid in this segment is independent of the presence of ADH SUMMARY: .Proximal tubule – water and solutes are in equal proportions reabsorbed . making the distal tubules which are continually reabsorbing solutes to be impermeable to water Concentrating the urine Requirements: 1.Excretion of a dilute or oncentration urine made without major changes in the excretion of solute (Na+ or K+) Antidiuretic hormone (ADH) . ACTIVE reabsorption of Na+. High levels of ADH 2.Operation of the COUNTERCURRENT mechanism .Renal excretion of water o Controlled by factors that influence GFR and tubular reabsorption Renal ways of excreting water .Allows more water reabsorption on the distal and collecting tubules and decreases the urine output Diluting the urine . Tubular fluid becomes dilute as it ascends the loop.- Total concentration of solutes in the ECF Amount of solutes divided by the volume of ECF Regulated by ECF water - Total body water . and Cl.while impermeable to water.Fluid leaving the ascending limb of the loop and early distal tubule is ALWAYS DILUTE REGARDLESS OF THE LEVEL OF ADH .Body water deficit – urine osmolarity can go as high as 1200 to 1400 mOsm/L (concentrated) .

As the fluid reach the inner medullary collecting duct.Reabsorption: as water flows into the ascending limb. it maintains its absorptive capacity through bulk flow due to the colloid osmotic and hydrostatic pressures that favour reabsorption in these capillaries.Urea from the medullary interstitium (from the inner medullary collecting duct) diffuses back into this segment Countercurrent mechanism 1. into the distal and cortical collecting duct – zero urea absorption due ti impermeability of these tubules. The ‘U’ shape capillary prevents the loss of solutes from the interstitium. Water diffusion out of the blood b. ADH increases the permeability of this segment to urea. Interstitial fluid osmolarity of the renal medullary area – 1200 to 1400 mOsm/L 3. the same as the plasma 2.Passively reabsorbed from the inner medullary collecting ducts .Tubular fluid becomes dilute ADH Supraoptic and paraventricular nuclei of hypothalamus  synthesis Posterior pituitary  storage Calcium entry in the nerve endings increase to affect membrane permeability when hypothalamic nuclei are stimulated  ADH release AV3V – anteroventral region of the 3rd ventricle (subfonical organ and the organum vasculosum of the lamina terminalis) - - . (permeable to ure). but preserves it by the diffusion of fluid and solutes into and out of the medullary interstitium and the blood. urea concentration inside the tubules increases. COUNTER CURRENT EXCHANGER The vasa recta does not create the medullary hyperosmolarity. It has accumulated large amounts of solutes in greater excess of water Role of Urea .Urea contributes about 40% (500 mOsm/L) of the renal medullary interstitium osmolarity . and consequent water reabsorption to the interstitium.- - Special anatomical arrangement of the loops of Henle and vasa recta (specialised peritubular capillaries) --. Interstitial fluids osmolarity in all parts of the body – 300 mOsm/L. THIN ASCENDING LOOP Impermeable to water More permeable to NaCl Some passive diffusion of NaCl in to the interstitium .Impermeable to water . with ADH.25% of human nephrons are JUXTAGLOMERULAR – loops of Henle and vasa recta extending deep into the medulla. before returning back to the cortex Role of the collecting ducts interstitium and water diffuses back into the vasa recta. In the ascending limb of the vasa recta. Plasma flowing form the descending limb of the vasa recta becomes hyperosmotic a. solutes diffuse back into the THICK ASCENDING LOOP . Solute diffusion from the renal interstitium into the blood 2.The tubular fluid becomes more dilute as it flows to the thick segment .Active transport of electrolytes . Though it minimizes solute loss from the interstitium. STEPS… 1. urea now diffuses into the interstitium.

- Osmoreceptors – neuronal cells excited by changes in ECF osmolarity. .