Urinary System Lecture Notes PDF

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Lecture notes on the urinary system...

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CHAPTER 23 – URINARY SYSTEM PART 2 1. URINARY SYSTEM ORGANS a. Six Organs i. 2 - Kidneys ii. 2 - Ureters iii. 1 - Bladder iv. 1 - Uretha 2. FUNCTIONS OF THE KIDNEY (890) a. Eliminates Waste i. Blood Plasma ii. Separates waste from useful chemicals iii. Returns useful substances to blood b. Regulate Blood Volume and Pressure i. By eliminating or conserving water c. Regulate the Osmolarity of Body Fluids i. By controlling the relative amounts of water and solutes eliminated 1. (electrolyte/water balance); ii. Regulates Acid/Base Balance (together with the lungs) d. Secretes i. Renin – enzyme which activates hormonal mechanisms that control blood pressure and electrolyte balance ii. Erythropoietin – a hormone which stimulates the production of red blood cells. iii. Calcitriol Synthesis – final step in synthesizing calcitriol which contributes to calcium homeostasis e. Gluconeogeneis from amino acids in extreme starvation 3. METABOLIC WASTES AND NITROGENOUS WASTES (890) a. Waste – any substance that is useless/toxic to the body or present in excess b. Metabolic Waste – waste substance produced by the body chemical reactions c. Nitrogenous Wastes i. Urea and ammonia 1. Proteins Amino Acids NH2 removed forms ammonia, liver converts to urea (less toxic) ii. Uric Acid – product of nucleic acid catabolism iii. Creatinine – product of creatine phosphate catabolism (muscle metabolism) 4. EXCRETION (891) a. Separation of wastes from body fluids and their elimination b. Four body systems carry out excretion i. Respiratory system 1. CO2 , small amounts of other gases and water ii. Integumentary system 1. Water, inorganic salts, lactic acid, urea in sweat. iii. Digestive System 1. Water, salts, CO2, lipids, bile pigments, cholesterol, other metabolic wastes, and food residue iv. Urinary System 1. Many metabolic wastes, toxins, drugs, hormones, salts, H+, and water

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5. GROSS ANATOMY OF THE KIDNEY (892) a. Connective Tissue Coverings i. Renal fascia: Fibrous capsule 1. outermost – binds it to abdominal wall Renal cortex ii. Fat capsule Renal medulla Renal papilla 1. middle layer, cushions kidney and holds it in Renal sinus Adipose tissue place Renal pelvis inMajor renal calyx sinus iii. Fibrous capsule: Minor calyx Renal column 1. Encloses kidney protecting it from trauma and Renal pyramid Ureter Renal blood infection vessels 2. Collagen fibers extend from fibrous capsule to renal fascia b. Renal Cortex i. Renal Cortex (0uter) c. Renal Medulla i. Renal Medulla (Inner) d. Renal Pyramids, i. 6 – 10 with broad base facing cortex and renal papilla facing sinus (medulla) e. Renal Columns i. Extensions of the cortex that project inward toward sinus f. Papilla g. Renal Sinus – at the medial concave hilum i. Contains blood and lymphatic vessels, nerves, and urine-collecting structures ii. Adipose fills the remaining cavity and holds structure into place. h. Lobe of kidney i. One pyramid and its overlaying cortex i. Minor calyxes i. Cup that collects urine from each papilla j. Major calyxes i. Convergence of two or three minor calyces k. Renal pelvis i. Convergence of 2 or 3 major calyces l. Ureter i. A continuation of the pelvis that drains the urine down to the urinary bladder 6. POSITION AND ASSOCIATED STRUCTURES (892) a. Position i. Lies at the posterior abdominal wall ii. Right kidney is slightly lower due to large right lobe of liver iii. Rib 12 crosses the middle of the left kidney iv. Retroperitoneal along the Ureters, urinary bladder, renal artery and vein, and adrenal glands (sits in its own sack) b. Shape and Size i. Size of a fist ii. Lateral surface is convex iii. Medial is concave with a slit called the hilum 1. Receives renal nerves, blood vessels, lymphatic, and Ureters 2

7. RENAL CIRCULATION (893) a. Kidneys account for only 0.4% of body weight b. They receive about 20% - 21% of the cardiac output (renal fraction) i. Renal artery 1. Divides into segmental arteries that give rise to ii. Interlobar Arteries up the renal columns between pyramid iii. Arcuate Arteries – base of pyramids iv. Interlobular Arteries – up into the cortex branch into afferent arterioles v. Afferent Arterioles – each supplying one nephron 1. Leads to a ball of capillaries in the glomerulus. vi. Cortex 1. Peritubular capillaries branch off of the efferent arterioles supplying the tissue near the glomerulus, the proximal and distal convoluted tubules vii. Medulla 1. The efferent arterioles give rise to the vasa recta, supplying the nephron loop 8. THE NEPHRON (894) a. Each kidney has about 1.2 million nephrons b. Nephron composed of two principal parts i. Renal corpuscle – filters the blood plasma

Key Flow of blood Flow of filtrate Afferent arteriole Blood flow Efferent arteriole (a)

Parietal layer Capsular space Podocytes of visceral layer Glomerulus Proximal convoluted Glomerular tubule capillaries (podocytes and capillary wall removed)

Blood flow

1. Consists of the glomerulus (capillaries) and a two-layered glomerular (Bowman) capsule that encloses the glomerulus a. Parietal (outer) layer of the Bowman Capsule is simple squamous epithelium b. Visceral (inner) layer of the Bowman capsule consists of elaborate cells called podocytes that wrap around the capillaries of the glomerulus. c. Capsular space – separates the 2 layers of the Bowman capsule ii. Renal (uriniferous) tubule – long coiled tube that converts the filtrate into urine 1. Duct that leads away from the glomerular capsule and ends at the tip of the medullary pyramid 2. Dived into Four Regions 3

Glomerular filtrate collects in capsular space, flows into Proximal Convoluted (PCT) – arises from the glomerular capsule proximal convoluteda. tubule. Note Tubule the vascular and i. Longest and most coiled region urinary poles. Note the afferent arteriole is larger than Simple cubodial epithelium with prominent microvilli for majority of ii. the efferent arteriole.

reabsortion b. Nephron Loop (Loop of Henle) – long U-shaped portion of the renal tubule i. Descending limb and ascending limb ii. Thick segments have simple cubodial epithelium 1. Initial part of descending limb and part or all of ascending limb 2. Heavily engaged in the active transport of salts and have many mitochondria iii. Thin segment have simple squamous epithelium 1. Forms lower part of descending limb 2. Cells very permeable to water c. Distal Convoluted Tubule (DCT) i. Shorter and less coiled that PCT ii. Simple cuboidal epithelium without microvilli iii. DCT is the end of the nephron d. Collecting Duct – receives fluid from the DCTs of several nephrons as it passes back into the medulla i. Numerous collecting ducts converge toward the tip of the medullary pyramid ii. Papillary Duct – formed by merger of several collecting ducts 1. Collecting and papillary ducts lined with simple cuboidal epithelium

9. FLOW OF FLUID a. The point where the glomerular filtrate is formed to the point where urine leaves the body glomerular capsule → proximal convoluted tubule → nephron loop → distal convoluted tubule → collecting duct → papillary duct → minor calyx → major calyx → renal pelvis → ureter → urinary bladder → urethra 10. MICROSCOPIC ANATOMY OF THE NEPHRON a. Cortical Nephrons i. 85% of all nephrons ii. Short nephron loops iii. Efferent arterioles branch into pertubular capillaries around PCT and DCT b. Juxtamedullary Nephrons i. 15% of all nephrons ii. Very long nephron loops iii. Maintain salinity gradient in the medulla iv. Helps conserve water v. Efferent arterioles branch into vasa recta around the long nephron loop c. Renal Plexus – Nerves and ganglia wrapped around each renal artery i. Issues nerve fibers to the blood vessels and convoluted tubules of the nephron 1. Sympathetic innervations (nerves) from the abdominal aortic plexus a. Stimulation reduces glomerular blood flow and rate of urine production 2. Parasympathetic innervations from the vagus nerve

11. URINE FORMATION AND WATER CONSERVATION 4

a. Urine Formation (1) i. (I) Glomerular Filtration 1. Glomerular filtrate - The fluid in the capsular space a. Similar to blood plasma except that it has almost no protein and blood cells b. Urine Formation (2) 1. (2) Tubular Fluid Reabsorption and Secretion – fluid from the proximal convoluted tubule through the distal convoluted tubule a. Secretion b. Substances removed or added by tubular cells c. Urine Formation (3) 1. Urine a. Fluid that enters the collecting duct i. Undergoes little alteration beyond this point except for changes in water content 12. GLOMERULAR FILTRATION MEMBRANE (urine formation 1) i. Glomerular Filtration - Water and some solutes in the blood plasma pass from the capillaries of the glomerulus into the capsular space of the nephron Filtration membrane has 3 barriers through which fluid passes (898) 1. Fenestated endothelium of glomerular capillaries i. 70 – 90 nm filtration pores exclude blood cells ii. Highly permeable 2. Basement membrane a. Proteoglycan gel, negative charge, excludes molecules greater than 8nm b. Albumin repelled by negative charge c. Blood plasma is 7% protein, the filtrate is only 0.03% protein 3. Visceral glomerular capsule layer (has filtration slits) a. Made up of podocytes b. Podocyte cell extensions (pedicels) wrap around the capillaries to form a barrier layer with 30nm filtration slits c. Negatively charged which is an additional obstacle for large anions ii. Filtration membrane almost any molecule smaller than 3nm can pass freely through the filtration membrane 1. Water 2. Electrolytes 3. Glucose 4. Fatty acids 5. Amino acids 6. Nitrogenous wastes 7. And Vitamins iii. Some substances of low molecular weight are bound to the plasma proteins and cannot get through the membrane 1. Most calcium 2. Iron 3. And Thyroid hormone a. Unbound fraction passes freely into the filtrate 13. FILTRATION PRESSURE (899) 5

a. Blood Hydrostatic Pressure (BHP) (out) i. Much higher in glomerular capillaries, 60mm Hg, compared to 10 50 15 in most other capillaries ii. Because afferent arteriole is larger than efferent arteriole iii. Larger inlet and smaller outlet b. Hydrostatic pressure in capsular space (Capsular Pressure) (out) i. 18mm Hg due to high filtration rate and continual accumulation of fluid in the capsule c. Colloid Osmotic Pressure (COP) of blood i. About 32mm Hg (in) ii. Glomerular filtrate is almost protein-free and has no significant COP

BHP 60 out COP 32 in CP 18 in

iii. Higher outward pressure of 60mm Hg, opposed by two inward pressures of 18 mm Hg and 32 mmHg NET FILTRATION PRESSURE 60OUT – 18IN – 32IN = 10 MM Hg OUT 14. THE FORCES INVOLVED IN GLOMERULAR Blood hydrostatic pressure (BHP) Colloid osmotic pressure (COP) FILTRATION Capsular pressure (CP) Net filtration pressure (NFP) a. High BP in glomerulus makes kidneys vulnerable to hypertensive damage i. It can lead to 1. rupture of glomerular capillaries 2. produce scarring of the kidneys (nephrosclerosis) 3. Atherosclerosis of renal blood vessels 4. Ultimately leading to renal failure 15. GLOMERULAR FILTRATION RATE (GFR) – a. The amount of filtrate formed per minute by the two kidneys combined i. GFR = 125mL/min. or 180 L/day (male) ii. GFR = 105 mL/min or 150 L/day (female) b. Net filtration pressure (NFP)

NFP 10 out

60 mm Hg -32 mm Hginout -18 mm Hgin 10 mm Hgout

c. Filtration coefficient (Kf) depends on permeability and surface area of filtration barrier. 99% of filtrate is reabsorbed since only 1 to 2 urine excreted per day 16. REGULATION OF GLOMERULAR FILTRATION a. GFR too high i. Fluid flows through the renal tubules too rapidly for them to reabsorb the usual amount of water and solutes ii. Urine output rises iii. Chance of dehydration and electrolyte depletion iv. Flow of tubular fluid increases and more NaCl is reabsorbed v. Macula densa stimulated JG cells with a paracrine vi. JG cells contract which constricts afferent arteriole, reducing GFR to normal OR vii. Mesangial cells may contract, constricting the capillaries and reducing filtration

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b. GFR too low i. Wastes reabsorbed ii. Azotemia may occur iii. Afferent arterioles and mesangial cells relax iv. Blood flow increases and GFR rises back to normal c. GFR Control i. By adjusting glomerular blood pressure constantly ii. Is achieved by three homeostatic mechanisms 1. Renal Autoregulation a. Methods of Autoregulation (2) i. Myogenic mechanism 1. Based on the tendency of smooth muscle to contract when stretched a. Increased arterial blood pressure stretches the afferent arteriole i. Arteriole constricts and prevents blood flow into the glomerulus from changing much (Vasoconstriction) b. When arterial blood pressure falls i. The afferent arteriole relaxes (Vasodilatation) ii. Allows blood flow more easily into the glomerulus iii. Filtration remains stable ii. Tubulaoglomerular feedback 1. Mechanism by which glomerulus receives feedback on the status of the downstream tubular fluid and adjusts filtration to regulate the composition of the fluid, stabilize its own performance, and compensates for fluctuation in systemic blood pressure a. Juxtaglomerular apparatus i. Complex structure found at the very end of the nephron loop where it has just reentered the renal cortex ii. 3 kinds of cells occur (Macula Densa, Juxtaglomerular, and Mesangial cells) iii. Macula densa – Patch of slender, closely spaced epithelial cells at the end of the nephron loop on the side of the tubules facing the arterioles Senses variations in flow or fluid composition and secretes a paracrine that stimulates JG cells iv. Juxtaglomerular (JG) Cells – enlarged smooth muscle cells on the afferent arteriole directly across from macula densa Stimulated by the macula paracrine secretions They dilate or constrict the arterioles v. Mesangial Cells in cleft between afferent and efferent arterioles and among capillaries of the glomerulus 7

Connected to the macula dens and JG cells by gap junctions and communicate by means of paracrines  Provide supportive matrix for glomerulus constrict or relax capillaries to regulate flow b. Loop comes into contact with the afferent and efferent arterioles at the vascular pole of the renal corpuscle i. Renal autoregulation cannot compensate for extreme blood pressure variation 1. Over a MAP range of 90 to 180 mm Hg, the GFR remains quite stable 2. Below 70 mm Hg, glomerulur filtration and urine output cease 3. Occurs in hypovolemic shock c. Nephrons adjust their blood flow and GFR without external (nervous or hormonal) control d. Enables them to maintain a relatively stable GFR in spite of changes in systemic arterial blood pressure 2. Sympathetic Control a. Sympathetic nervous system and adrenal epinephrine constrict the afferent arterioles in strenuous exercise or acute conditions like circulatory shock i. Reduces GFR and urine output ii. Redirects blood from the kidneys to the heart, brain, and skeletal muscles 3. Hormonal Control – Renin-Angiotensin-Aldosterone Mechanism a. Renin i. Renin secteted by JG cells if drops dramatically ii. Renin converts angiotensinogen a blood protein, into angiotensin I iii. In the lung and kidneys, angiotensin – converting enzyme (ACE) converts angiotensin I to angiotensin II the active hormone 1. Works in several ways to restore fluid volume and BP b. Angiotensin II i. Potent vasoconstrictor, raises BP throughout body 1. Constricts efferent arteriole, raises GFR despite low BP 2. Lowers BP in peritubular capillaries enhancing reabsorption of NaCl and H20 ii. Stimulates adrenal cortex to secrete aldosterone promoting Na+ and H2O reabsorption in DCT and collecting duct iii. Stimulates posterior pituitary to secrete ADH which promotes water reabsorption by the collecting duct 1. Stimulates thirst and H2O intake 

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17. NEGATIVE FEEDBACK CONTROL OF GFR Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

High GFR

Reduced GFR

Rapid flow of filtrate in renal tubules

Constriction of afferent arteriole

Sensed by macula densa

Paracrine secretion

18. BASIC STAGES OF URINE FORMATION a. Conversion of glomerular filtrate to urine involves the removal and addition of chemicals by tubular reabsorption and secretion i. Occurs through PCT to DCT ii. Tubular fluid is modified b. Steps involved include i. Tubular Reabsorption ii. Tubular Secretion Water conservation also occurs in the renal tubules 19. PROXIMAL CONVOLUTED TUBULE a. PCT reabsorbs about 65% of glomerular filtrate, removes some substances from the blood, and secretes them into the tubular fluid for disposal in urine i. Prominent microvilli and great length ii. Abundant mitochondria provide ATP for active transport iii. PCTs alone account for about 6% of one’s resting ATP and calorie consumption b. Tubular reabsorption – process of reclaiming water and solutes from the tubular fluid and returning then to the blood i. Sodium Reabsoprtion – is the key to everything else 1. Creates an osmotic and electrical gradient that drives the reabsorption of water and other solutes 2. Most abundant cation in filtrate 3. Creates steep concentration gradient that favors its diffusion into the epithelial cells 4. Symports Proteins – Simultaneously bind Na+ and another solute such as glucose, amino acids, or lactate 5. Na+ - H+ antiport proteins – pulls Na+ into the cell while pumping out H+ into tubular fluid ii. Sodium is prevented from accumulating in the epithelial cells by Na+ - K+ pumps (active transport) in the basal surface of the epithelium 1. Pupmps Na+ out into the extracellular fluid 2. Picked up by peritubular capillaries and returned to the bloodstream 9

3. Secondary active transport – Na+ transporting symports in apical cell membrane are passive a. Considered an example of secondary active transport for their dependence on the Na+ - K+ pumps at the base of the cell iii. Chloride ions follow the positive sodium ions by electrical attraction iv. Use various antiport systems; exchange with other anions v. Potassium, magnesium and phosphate ions diffuse through the paracellular route with water vi. Phosphate is also cotransported into the epithelial cells with Na+ vii. Some calcium is reabsorbed through the paracellular rout in the PCT, but most Ca2+ occurs later in the nephron loop viii. Glucose is cotransported with Na+ by sodium-glucose transport (SGLT) proteins ix. Urea diffuses through the tubule epithelium with water – reabsorbs 40% - 60% in tubular fluid 1. Kidneys remove about half of the urea from the blood; creatinine is not reabsorbed at all x. 2/3 of water in filtrate is reabsorbed by the PCT (180 L of glomerular filtrate reduced to 1 or 2 L urine each day) xi. Reabsorption of all the salt and organic solutes makes the tubule cells and tissue fluid hypertonic 1. Water follows solutes by osmosis through both paracellular and transcellular routes through water channels called aquaporins 2. In PCT, water is reabsorbed at constant rate called obligatory water reabsorption c. 2 Routes of reabsorption i. Transcellular route 1. Substances pass through the cytoplasm of the PCT epithelial cells and out their base ii. Paracellular route 1. Substances pass between PCT cells 2. Solvent drag – water carries with it a variety of dissolved solutes Taken up by the peritubular capillaries 20. TRANSPORT MAXIMUM a. There is a limit to the amount of solute that the renal tubules can reabsorb b. Limited by the number of transport proteins in the plasma membrane c. If all transporters are occupied as solute molecules pass i. Excess solutes appear in urine d. Transport maximum is reached when transporters are saturated e. Each solute has its own transport maximum i. Any blood glucose level above 220 mg/dL results in glycosuria f. Tubular secretion – process in which renal tubule extracts chemicals from capillary blood and secretes them into tubular fluid g. Two purposes in proximal convoluted tubule and nephron loop i. Waste Removal 1. Urea, uric acid, bile acids, ammonia, catecholamines, prostaglandins, and a little creatinine are secreted into the tubule 2. Secretion of uric acid compensates for its reabsorption earlier in PCT 3. C...