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• Is to regulate plasma and interstitial fluid composition by formation of urine • More specifically, kidneys regulate:
– Volume of blood plasma, which contributes to BP – Waste products in blood – Concentration of electrolytes in blood
• Including Na+, K+, HCO3- , and others
– Plasma pH (H+)
Structure of Urinary System
• Paired kidneys are on both sides of vertebral column below diaphragm
– About size of fist
• Urine flows from kidneys into ureters which transport it to urinary bladder
Structure of Kidney
• Cortex contains many capillaries and outer parts of nephrons • Medulla consists of renal pyramids separated by renal columns • Pyramids empty urine into minor calyces which unite to form a major calyx
Structure of Kidney
• Pyramids empty urine into minor calyces which unite to form a major calyx
Structure of Kidneys continued • Major calyces join to form renal pelvis which collects urine – Conducts urine to ureters which empty into bladder – Bladder has a smooth muscle wall called the detrussor muscle 17-7 .
Micturition Reflex (Urination) continued • Actions of internal and external urethral sphincters are regulated by reflex center located in sacral part of spinal cord • Filling of bladder activates stretch receptors that send impulses to micturition reflex center – This activates Parasympathetic neurons causing slight contraction of detrusor muscle that pushes open the internal urethral sphincter creating sense of urgency – There is voluntary control over external urethral sphincter (relaxes) – Urination is then consciously initiated 17-9 .
25 million nephrons/kidney • Is a long tube and has associated blood vessels . responsible for forming urine – >1.The Nephron • Is the structural/functional unit of kidney.
Nephron Tubules and Blood Vessels .
Glomerular (Bowman's) Capsule • Surrounds glomerulus • Is where glomerular filtration occurs – Capsule collects and directs filtrate into Proximal Convoluted Tubule 17-16 .
Glomerular Filtration • Glomerular capillaries and Bowman's capsule form a filter for blood – Glomerular capillaries are fenestrated (ie: have large pores between their endothelial cells) • Big enough to allow any plasma molecule to pass • 100-400 times more permeable than other capillaries 17-20 .
Glomerular Filtration continued • To enter tubule filtrate must pass through narrow slit diaphragms formed between pedicels (foot processes) of podocytes of glomerular capsule 17-21 .
a lot of protein appears in the urine (=proteinuria).glomerulonephritis 17-22 .Glomerular Filtration continued • Plasma proteins are mostly excluded from the filtrate because of their large size and negative charge – The slit diaphragms are lined with a basement membrane composed of negative charges which repel negatively-charged proteins – Some protein (especially albumin) normally enters the filtrate but most is reabsorbed by receptormediated endocytosis • In some diseases.
whose filtration was driven by blood pressure 17-25 .Glomerular Ultrafiltrate • Is the fluid that enters glomerular capsule.
125 ml/min in men – Totals about 180L/day (45 gallons) • So most filtered water must be reabsorbed or death would ensue from water lost through urination 17-26 .Glomerular Filtration Rate (GFR) • Is volume of ultrafiltrate produced by both kidneys/min – Averages 115 ml/min in women.
Measurement of Renal Blood Flow • Not all blood delivered to glomerulus is filtered into glomerular capsule – 20% is filtered. rest passes into efferent arteriole and back into circulation – Substances that aren't filtered can still be cleared by active transport (tubular secretion) into tubules further down nephron tubules 17-58 .
Regulation of GFR • GFR is controlled by extrinsic and intrinsic (autoregulation) mechanisms • Vasoconstriction or dilation of afferent arterioles affects rate of blood flow into glomeruli and thus GFR 17-27 .
Sympathetic Effects • Sympathetic activity during exercise constricts afferent arterioles – Extrinsic regulation of GFR – Significantly slows GFR – Helps maintain blood volume and pressure and shunts blood to heart and muscles 17-28 .
afferent arterioles dilate • When mean arterial pressure (MAP) increases.Renal Autoregulation (Intrinsic) • Allows kidney to maintain a constant GFR over a wide range of fluctuating BPs • Achieved via effects of locally produced chemicals on afferent arterioles • When mean arterial pressure (MAP) drops to 70 mm Hg. afferent arterioles constrict 17-29 .
The Three Processes of Urine Formation Urine is formed by three Processes: .Tubular Secretion: movement of wastes/excess materials from blood into renal tubules .Tubular Reabsorption: movement of nutrients from renal tubules back into blood .Glomerular Filtration: movement of materials from glomerulus into nephron .
only 1–2 L of urine excreted/24 hours • Urine volume varies according to needs of body • Minimum of 400 ml/day = urine necessary to excrete metabolic wastes (obligatory water loss) 17-33 .Reabsorption of Salt and H2O • The PCT returns most molecules and H2O from filtrate back into peritubular capillaries by tubular reabsorption: – About 180 L/day of ultrafiltrate produced.
to passively follow Na+ • Water then follows salt by osmosis 17-35 .Proximal Convoluted Tubule • Ultrafiltrate in PCT is isosmotic to blood (300 mOsm/L) • Thus reabsorption of H2O by osmosis cannot occur without active transport (AT) – Is achieved by AT of Na+ out of filtrate • Loss of + charges causes Cl.
Cl-.Significance of PCT Reabsorption • ~65% Na+. depending on level of body hydration 17-37 . and H2O is reabsorbed in PCT and returned to bloodstream • An additional 20% is reabsorbed in descending loop of Henle • Thus 85% of filtered H2O and salt are reabsorbed early in nephron – This is at a constant rate and independent of body hydration levels – The remaining 15% is reabsorbed variably.
Concentration Gradient in Kidney • In order for H2O to be reabsorbed. interstitial fluid of kidney must be hypertonic to ultrafiltrate • Osmolality of medullary interstitial fluid (12001400 mOsm) is 4X that of renal cortex and plasma (300 mOsm) – This concentration gradient results largely from loop of Henle which allows interaction between descending and ascending limbs 17-38 .
Descending Limb Loop of Henle • Is permeable to H2O • Is impermeable to. salt • Because deep regions of medulla are hypertonic. and does not actively transport. H2O diffuses out of filtrate into interstitial fluid – This reabsorbed H2O is then collected by capillaries 17-39 .
thick part provides active transport of salt out of filtrate – AT of salt causes interstitial fluid to become hypertonic to ultrafiltrate 17-40 .Ascending Limb Loop of Henle • Is impermeable to H2O but permeable to salt.
Countercurrent Multiplier System • Countercurrent flow and proximity allow descending and ascending limbs of LH to interact in way that causes osmolality to build in medulla 17-43 .
it causes even higher osmolality around descending limb (positive feedback) 17-43 . causing more H2O to diffuse out of filtrate – This raises osmolality of filtrate in descending limb which causes more concentrated filtrate to be delivered to ascending limb – As this concentrated filtrate is subjected to AT of salts.Countercurrent Multiplier System • Salt pumping in thick ascending limb raises osmolality around descending limb.
trapping some in medullary interstitial fluid • Reabsorbs H2O coming out of descending limb • Traps solutes but allows water to be reabsorbed back into systemic circulation 17-44 . H2O (via aquaporins) • Recirculates salt.Vasa Recta • Permeable to salt.
Effects of Urea • Urea contributes to high osmolality in medullary region – Deep region of collecting duct is permeable to urea and it is reabsorbed – Ascending limb absorbs urea – Thus urea is trapped in medullary area 17-45 .
Collecting Duct (CD) • Plays important role in water conservation • Is impermeable to salt • Permeability to H2O depends on levels of ADH 17-47 .
Antidiuretic Hormone • Is secreted by posterior pituitary in response to dehydration • Stimulates opening of aquaporins (water channels) of collecting duct (CD) • When ADH is high. H2O is drawn out of CD by high osmolality of medullary interstitial fluid – And then reabsorbed by vasa recta 17-48 .
Renal Clearance • Refers to ability of kidney to remove substances from blood and excrete them in urine • Occurs by filtration and by secretion • Secretion is opposite of reabsorption--substances from vasa recta are transported into tubule and excreted • Reabsorption decreases renal clearance. secretion increases clearance 17-51 .
Renal Clearance • Excretion rate = (filtration rate + secretion rate) .reabsorption rate 17-52 .
Renal Clearance of Inulin Since it is not reabsorbed nor secreted. the amount of inulin in the urine is an exact indication of GFR 17-55 .
Renal Clearance of a Molecule Also Secreted 17-60 .
Glucose and Amino Acid Reabsorption • Filtered glucose and amino acids are normally completely reabsorbed from ultrafiltrate – Occurs in PCT by cotransport with Na+ • Transporter displays saturation if ligand concentration in ultrafiltrate is too high – Level that saturates carriers and achieves maximum transport rate is transport maximum (Tm) – Glucose and amino acid transporters aren’t saturated under normal conditions 17-61 .
Glycosuria • Is presence of glucose in urine • Occurs when glucose > 180-200mg/100ml plasma (= renal plasma threshold) – Glucose is normally absent from urine because plasma levels stay below this level – Hyperglycemia has to exceed renal plasma threshold to cause glycosuria – Diabetes mellitus occurs when chronic hyperglycemia results in glycosuria 17-62 .
Renal Control of Electrolyte Balance • Kidneys regulate levels of Na+. and PO4-3 by matching excretion to ingestion • Control of plasma Na+ is important in regulation of blood volume and pressure • Control of plasma of K+ is important in proper function of cardiac and skeletal muscles 17-64 . HCO3-. H+. Cl-. K+.
Control of Electrolyte Balance Role of Aldosterone in Na+/K+ Balance • 85% filtered Na+ and K+ reabsorbed before DCT – Remaining (15%) is variably reabsorbed in DCT and CD according to bodily needs • Regulated by aldosterone (controls K+ secretion/excretion and Na+ reabsorption/retention) • In the absence of aldosterone secretion. some of the remaining 15% of Na+ is reabsorbed in DCT and CD • When aldosterone is high in circulation ALL remaining Na+ is reabsorbed (thus none in the urine) 17-65 .
all K+ is reabsorbed and none excreted K+ Secretion 17-66 .• Is the only way K+ is excreted in urine • Is directed by aldosterone and occurs in DCT and CD – High blood K+ or low blood Na+ will increase circulatory aldosterone and thus K+ secretion – In absence of aldosterone.
Control of Electrolyte Balance The Juxtaglomerular Apparatus (JGA) • A specialized region in each nephron where afferent arteriole comes in contact with ascending limb and distal convoluted tubule 17-67 .
Control of Electrolyte Balance Renin-Angiotensin-Aldosterone System (RAAS) • Begins with release of renin from granular cells of afferent arteriole due to low blood volume (thus pressure) and low flow in afferent arteriole: – Renin converts plasma angiotensinogen to angiotensin I • Which is then converted to Angio II by angiotensin-converting enzyme (ACE) in lungs • Angio II stimulates release of aldosterone from adrenal cortex • Aldosterone stimulates Na+ reabsorption • Chloride and water follows and blood pressure is increased 17-68 .
Control of Electrolyte Balance • Is region of ascending limb in contact with afferent arteriole • Work opposite of RAAS • Cells respond to levels of Na+ in ultrafiltrate Macula Densa Cells – Inhibit renin secretion when Na+ levels are high – Causing less aldosterone secretion. thus more Na+ excretion – Lowers BP 17-71 .
Control of Electrolyte Balance Atrial Natriuretic Peptide (ANP) • • • • Is produced by atria due to stretching of walls Acts opposite to aldosterone Stimulates salt and H2O excretion Acts as a diuretic and a natriuretic 17-73 .
in severe acidosis.Control of Electrolyte Balance Na+. and H+ Relationship • Na+ reabsorption in DCT and CD creates electrical gradient for H+ or K+ secretion – Hyperkalemia can cause acidosis because K+ is secreted at expense of H+ • Comparatively. H+ is secreted at expense of K+ results in hyperkalemia 17-75 . K+.
and excrete excess H+ 17-76 .Renal Acid-Base Regulation • Kidneys help regulate blood pH by excreting H+ and/or reabsorbing HCO3• Most H+ secretion occurs across walls of PCT in exchange for Na+ reabsorption (Na+/H+ antiporter) • Normal urine is slightly acidic (pH = 5-7) because kidneys reabsorb almost all HCO3.
congestive heart failure. or edema • Increase volume of urine by increasing proportion of glomerular filtrate that is excreted 17-81 .Diuretics • Are used to lower blood volume because of hypertension.
Diuretics • Loop diuretics are most powerful.is reabsorbed • Osmotic diuretics increase osmotic pressure of filtrate 17-81 . inhibit ActiveTransport of salt in thick ascending limb of LH Thiazide diuretics inhibit NaCl reabsorption in 1st part of DCT • Carbonic anhydrase inhibitors prevent H2O reabsorption in PCT when HCOs.
Sites of Action of Clinical Diuretics 17-82 .