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The urinary system
- 1. THE URINARY SYSTEM PP 121 DEPARTMENT OF PHARMACEUTICAL BIOLOGY FACULTY OF PHARMACEUTICAL SCIENCES
- 2. LEARNING OUTCOMES • The gross anatomy of the kidney, its circulatory system and definition of a nephron. • The five major portions of a nephron, including their structural adaptations and functions in urine formation. • The microscopic structure of a renal corpuscle and its filtrationmembrane. • The components of the juxtaglomerular apparatus and itssignificance.
- 3. Kidney: External Anatomy Lie in a retroperitoneal position in the superior lumbar region; protected by lower part of rib cage Paired, bean-shaped, 12cm long x 6cm wide x 3cm thick, ~150 g each The renal hilum lies in medial surface; the ureter, blood vessels, lymphatics and nerves all join each kidney at the hilum.
- 6. Kidney: External Anatomy Covered by 3 layers of supportive tissues: –renal fascia- outer most, fibrous layer, anchor kidneys to surrounding structures. – peri renal fat capsule- a fatty mass, cushions kidneys from blows. –fibrous capsule – prevents infections in surrounding regions from spreading to the kidney
- 7. Kidney: Internal Anatomy 1. Renal cortex 2. Renal medulla • Cone-shaped tissues, renal pyramids • Renal columns, separates the pyramids • Renal pelvis, continuous with the ureter 3. Calyx • Extensions (calyces) of pelvis • collect urine draining from the papilla and empty it into the renal pelvis, then ureter.
- 9. BLOOD SUPPLY •The kidney receive 25% (1200mL) of the total cardiac output perminute 9
- 10. Nephrons • Nephrons: the structural & functional units of kidneys • Each nephron consist of a glomerulus (a high- pressure capillary bed) • and a renal tubule. • Subdivisions of renal tubule: glomerular capsule,
- 11. Nephrons • Proximal convoluted tubule (PCT), loop of Henle (descending and ascending limbs), and distal convoluted tubule (DCT). • Renal Corpuscle= Glomerulus + glomerular capsule. • Collecting ducts receive urine from many nephrons and help concentrate urine.
- 12. Nephrons • Endothelium of the glomerular capillaries = fenestrated capillary – allows fluids pass from the blood into the glomerular capsule • • Parietal layer of the glomerular capsule= simple squamous epithelium • • Visceral layer of the glomerular capsule = consists of podocytes which terminate in foot processes • – Filtrate enters the capsular space through the filtration slits between the foot processes
- 15. Proximal Convoluted Tubule (PCT) • Wall of PCT formed by cuboidal epithelial cells with microvilli on outer surface • Microvilli increases the surface area and capacity of reabsorbing water and solutes from the filtrate. • Reabsorbs all the glucose, lactate, amino acids, 65% of Na+ and obligatory water reabsorption
- 16. • Lining of PCT contains many protein channels to carry out both active and passive transport • Epithelium of PCT also prevents the reabsorption of waste products – tight junctions • 70% water, Na. 100 % glu, aa.
- 17. Loop of Henle • Thin segment: simple squamous epithelium, permeable to water • Thick segment: cuboidal epithelium • Descending limb: impermeable to Na+, permeable to water • Ascending limb: impermeable to water, permeable to Na+
- 19. Distal Convoluted Tubule, DCT • Cuboidal, lack of microvilli • Reabsorption depends on the body’s needs • Reabsorption of water & Na+ regulates by hormones (ADH and aldosterone respectively)
- 21. Collecting Duct • Heterogeneous of cells • Intercalated cells: cuboidal cells with microvilli, principal cells • (with sparse, short microvilli) • Important in maintaining the acid-base balance of theblood • Principal cells help maintain the body’s water and Na+ balance
- 24. Types of Nephron 1. Cortical nephrons – 85% located almost entirely in the cortex; only small part of loop of Henle penetrates into the medulla Efferent arterioles supply peritubular capillaries 2. Juxtamedullary nephrons – 15% Glomeruli located in the cortex-medulla junction, its loop of Henle deeps into the medulla Together with vasa recta (capillary bed), it establishes medulla osmotic gradient which important in concentrated urine production.
- 25. Juxtagmedullary nephron Cortical nephron Peritubular capillaries Vasa recta capillaries Loop of Henle Loop of Henle 21
- 26. Nephron Capillary Beds • Glomerulus-produces the filtrate –Fenestrated capillary –Fed and drained by afferent and efferent arterioles respectively –Its blood pressure is high due to (i) high resistance in arterioles (ii) afferent arteriole has a larger diameter than the efferent –High blood pressure forces fluid and solute out of the blood into the glomerular capsule –Most of the filtrate (99%) is reabsorbed by the renal tubule cells and returned to the blood to the peritubular capillary beds
- 27. Nephron Capillary Beds Peritubular capillaries – reclaims most of that filtrate – Arise from the efferent arterioles of cortical nephrons – Low pressure, porous capillaries readily absorb solutes and water from the tubule cells Vasa recta- serving the loops of Henle of juxtamedullary nephrons – Arise from the efferent arterioles of juxtamedullary nephrons. – Concentrate urine.
- 28. Juxtaglomerular Apparatus Regulate the filtrate formation rate & systemic blood pressure. 3 cellular components: 1. Granular cells (juxtaglomerular cells) – Smooth muscle cells with secretory granules containing renin – Act as mechanoreceptors that sense BP in the afferentarteriole • Found between the vascular pole of the renal corpuscle and the returning distal convoluted tubule of the same nephron
- 31. Juxtaglomerular Apparatus 2. Macula densa cells – Chemoreceptors that respond to changes in the NaCl content of the filtrate, rich in ascending limb of loop of Henle 3. Extra-glomerular mesangial cells – Pass signals between macula densa and granular cells
- 33. The Filtration Membrane •Lies between the blood and the interior of the glomerular capsule •A porous membrane - passage of water and solutes smaller than plasma protein •3 layers: (i) fenestrated endothelium of the g. capillary (ii) visceral membrane/podocytes layer of the g. capsule (iii) between i & ii , the basement membrane composed of the basal lamina. •Fenestrations allow passage of all plasma components except blood cells. • Basement membrane restricts passage of large proteins/macromolecules.
- 35. Mechanism of Urine Formation • Step 1: Glomerular filtration • Step 2: Tubular reabsorption • Step 3: Tubular secretion • • Kidney regulates the volume, composition, and pH of the blood and eliminate nitrogenous metabolic wastes.
- 36. Step 1: Glomerular Filtration • Glomerular filtration = passive process • Glomeruli = filters, its products=filtrate – Filtrate components =similar to plasma but essentially protein free and devoid of RBC • Diameter of afferent arterioles --> efferent arterioles high -> glomerular BP allow for efficient filtration • Water, glucose, aminoacids and nitrogenous waste pass freely from blood into the glomerular capsule
- 37. Tubular Reabsorption • Tubular reabsorption = selective transepithelial process that begins as the filtrate enters the proximal tubules • All organic nutrients e.g glucose and amino acid are completely reabsorbed. • Reabsorption of water and many ions is continuously regulated and adjusted. • Reabsorption process may be passive or active
- 38. Tubular Secretion • Adding substances to the filtrate, either from the blood or tubule cells • Major site: PCT • An active process that important in eliminating drugs, metabolites, end products, excess ions and in maintaining the acid-base balance of the blood.
- 39. Tubular Secretion 1. Eliminating drugs, metabolites that bound to plasma proteins • - Plasma proteins not filtered the substances they bind are not filtered and so must be secreted. 2. Eliminating unwanted substances or end products that have been reabsorbed by passive process • E.g urea and uric acid
- 40. Step 3: Tubular Secretion • 3. Ridding the body of excess potassium ions • All potassium ions present in the filtrate is reabsorbed in the PCT and ascending loop of Henle • – Excess potassium ions is secreted through aldosterone- driven active tubular secretion into the DCT and collecting ducts • 4. Controlling blood pH • When blood pH ↓, the renal tubule actively secrete more H+ into the filtrate; retain & generate more HCO3- • – When blood pH ↑, Cl- is reabsorbed
- 41. Controlling Blood pH • • When pH ↓, the renal tubule cells secrete more H+ into the filtrate and retain and generate more HCO3- pH rises to its normal range • • When blood pH ↑, Cl- & H+ are reabsorbed pH drops to its normal range
- 44. In the thick ascending limb- Sodium is pumped out and chloride follows; making the medulla more concentrated and saltier. Water leaves passively from the thin descending limb because of the surrounding Na concentration this causes the GFR more concentrated. Water is also moves out of the collecting ducts. Countercurrent multiplication in the kidneys is the process of using energy to generate an osmotic gradient that enables you to reabsorb water from the tubular fluid and produce concentrated urine.
- 45. Renal Functions o Filter 200 liters of fluid from the blood stream each day! o Excretory functions – excrete toxins, metabolic wastes, excess ions while returning needed substances to the blood. o Regulate blood volume & chemical composition o Regulate water-salt and acid-base balances o Gluconeogenesis o Produces renin (regulates blood pressure) o Produces erythropoietin (stimulates RBC production). o Metabolizes vitamin D to its active form
- 46. urination reflex’ Micturition reflex The micturition reflex is one of the autonomic reflexes, but the release of urine is regulated by voluntary neural mechanisms that involve centers in the brain and spinal cord. The micturition reflex is a bladder-to-bladder contraction reflex for which the reflex center is located in the pontine micturition center (PMC). The Pontine micturition center (PMC, also known as Barrington's nucleus) is a collection of neuronal cell bodies located in the rostral pons in the brainstem involved in the supraspinal regulation of micturition. When activated, the PMC relaxes the urethral sphincter allowing for micturition to occur
Editor's Notes
- The urinary system consists of two kidneys, two ureters, the urinary bladder, and the urethra. The formation of urine is the function of the kidneys, and the rest of the system is responsible for eliminating the urine. Body cells produce waste products such as urea, creatinine, and ammonia, which must be removed from the blood before they accumulate to toxic levels. As the kidneys form urine to excrete these waste products, they also accomplish several other important functions: 1. Regulation of the volume of blood by excretion or conservation of water 2. Regulation of the electrolyte content of the blood by the excretion or conservation of minerals 3. Regulation of the acid–base balance of the blood by excretion or conservation of ions such as H ions or HCO3 ions 4. Regulation of all of the above in tissue fluid The process of urine formation, therefore, helps maintain the normal composition, volume, and pH of both blood and tissue fluid by removing those substances that would upset the normal constancy and balance of these extracellular fluids.
- https://www.youtube.com/watch?v=805VoHIIQCs
- The two kidneys are located in the upper abdominal cavity on either side of the vertebral column, behind the peritoneum (retroperitoneal). The upper portions of the kidneys rest on the lower surface of the diaphragm and are enclosed and protected by the lower rib cage. Each kidney has an indentation called the hilus on its medial side. At the hilus, the renal artery enters the kidney, and the renal vein and ureter emerge
- INTERNAL STRUCTURE OF THE KIDNEY In a coronal or frontal section of the kidney, three areas can be distinguished The lateral and middle areas are tissue layers, and the medial area at the hilus is a cavity. The outer tissue layer is called the renal cortex; it is made of renal corpuscles and convoluted tubules. These are parts of the nephron . The inner tissue layer is the renal medulla, which is made of loops of Henle and collecting tubules (also parts of the nephron). The renal medulla consists of wedge-shaped pieces called renal pyramids. The tip of each pyramid is its apex or papilla. The third area is the renal pelvis; this is not a layer of tissues, but rather a cavity formed by the expansion of the ureter within the kidney at the hilus. Funnel shaped extensions of the renal pelvis, called calyces (singular: calyx), enclose the papillae of the renal pyramids. Urine flows from the renal pyramids into the calyces, then to the renal pelvis and out into the ureter The renal arteries deliver to the kidneys of a normal person at rest 1.2 litres of blood per minute, a volume equivalent to approximately one-quarter of the heart’s output. Thus, a volume of blood equal to all that found in the body of an adult human being is processed by the kidneys once every four to five minutes.
- The two kidneys lie on the posterior wall of the abdomen, outside the peritoneal cavity. Each kidney of the adult human weighs about 150 grams and is about the size of a clenched fist. Each human kidney contains about 800,000 to 1,000,000 nephrons, each of which is capable of forming urine. The kidney cannot regenerate new nephrons. Therefore, with renal injury, disease, or normal aging, the number of nephrons gradually decreases. After age 40 years, the number of functioning nephrons usually decreases about 10% every 10 years; thus, at age 80 years, many people have 40% fewer functioning nephrons than they did at age 40 years. This loss is not life-threatening because adaptive changes in the remaining nephrons allow them to excrete the proper amounts of water, electrolytes, and waste products,
- The kidneys are embedded in adipose tissue that acts as a cushion and is in turn covered by a fibrous connective tissue membrane called the renal fascia, which helps hold the kidneys in place
- The papillae are bundles of collecting ducts that transport urine made by nephrons to the calyces of the kidney for excretion.
- The renal columns also serve to divide the kidney into 6–8 lobes and provide a supportive framework for vessels that enter and exit the cortex. The pyramids and renal columns taken together constitute the kidney lobes.
- BLOOD VESSELS OF THE KIDNEY: The pathway of blood flow through the kidney is an essential part of the process of urine formation. Blood from the abdominal aorta enters the renal artery, which branches extensively within the kidney into smaller arteries. The smallest arteries give rise to afferent arterioles in the renal cortex. From the afferent arterioles, blood flows into the glomeruli (capillaries), to efferent arterioles, to peritubular capillaries, to veins within the kidney, to the renal vein, and finally to the inferior vena cava. https://www.youtube.com/watch?v=_gMXdqpuWMY Interlobular artery makes branches and invades into the bowmans capsule
- https://www.youtube.com/watch?v=EZhYTnRiPaA The nephron is the structural and functional unit of the kidney. Each kidney contains approximately 1 million nephrons. It is in the nephrons, with their associated blood vessels, that urine is formed. Each nephron has two major portions: a renal corpuscle and a renal tubule.
- Renal Corpuscle A renal corpuscle consists of a glomerulus surrounded by a Bowman’s capsule. The glomerulus is a capillary network that arises from an afferent arteriole and empties into an efferent arteriole. Bowman’s capsule (or glomerular capsule) is the expanded end of a renal tubule; it encloses the glomerulus. The inner layer of Bowman’s capsule is made of podocytes; the name means “foot cells,” and the “feet” of the podocytes are on the surface of the glomerular capillaries. The arrangement of podocytes creates pores, spaces between adjacent “feet,” which make this layer very permeable. The renal tubule continues from Bowman’s capsule and consists of the following parts: proximal convoluted tubule (in the renal cortex), loop of Henle (or loop of the nephron, in the renal medulla), and distal convoluted tubule (in the renal cortex). The distal convoluted tubules from several nephrons empty into a collecting tubule. Renal corpuscle- blood filtering component of nephron Peritubular capillaries surround the proximal and distal tubules, as well as the loop of Henle, where they are known as vasa recta
- https://www.youtube.com/watch?v=fAOkr4SXbTM Podocytes (or visceral epithelial cells) are terminally differentiated cells lining the outer surface of the glomerular capillaries.
- These two layers are formed from one continuous sheet of cells that differ in structure and function. The parietal layer comprises Bowman's capsule and the cells are squamous, whereas the visceral layer is composed of the podocytes that have a more cuboidal shape and play a role in filtration of blood. Proximal tubules require more active transport mechanisms than other renal cell types because they reabsorb 80% of the filtrate that passes through the glomerulus, including glucose, ions, and nutrients. As such, they contain more mitochondria than any other structure in the kidney. Epithelial cells in the proximal convoluted tubule (PCT) reabsorb components of the glomerular filtrate that have nutritional significance (e.g., glucose, ions and amino acids). To facilitate absorption, these cells have numerous microvilli, Mv, along their apical surface. First, the proximal convoluted tubule - which is the longest part of the renal tubule - has a simple tall cuboidal epithelium, with a brush border (microvilli). The epithelium almost fills the lumen, and the microvilli increases the surface area by 30-40 fold. The DCT is lined with simple cuboidal cells that are shorter than those of the proximal convoluted tubule (PCT). The lumen appears larger in DCT than the PCT lumen because the PCT has a brush border (microvilli). The tissue type of the loop is simple squamous epithelium. The "thick" and "thin" terminology does not refer to the size of the lumen, but to the size of the epithelial cells. The loop is also sometimes called the Nephron loop. The collecting ducts are composed of two cell types: principal and intercalated cells. Principal or light cells are the most numerous and are characterized by a pale cytoplasm with sparse organelles. Principal cells increase in size from the cortex to the medulla and are largest in the papillary ducts. Intercalated cells are epithelial cells traditionally associated with the regulation of acid-base homeostasis in distal segments of the kidney tubule
- Loop of Henle, long U-shaped portion of the tubule that conducts urine within each nephron of the kidney of reptiles, birds, and mammals. The principal function of the loop of Henle is in the recovery of water and sodium chloride from urine. This function allows production of urine that is far more concentrated than blood, limiting the amount of water needed as intake for survival. Anatomically, the loop of Henle can be divided into three main segments: the thin descending limb, the thin ascending limb, and the thick ascending limb (sometimes also called the diluting segment). The first segment of the loop, the thin descending limb, is permeable to water, and the liquid reaching the bend of the loop is much richer in salt and urea than the blood plasma is. As the liquid returns through the thin ascending limb, sodium chloride diffuses out of the tubule into the surrounding tissue, where its concentration is lower. In the third segment of the loop, the thick ascending limb, the tubule wall can, if necessary, effect further removal of salt, even against the concentration gradient, in an active-transport process requiring the expenditure of energy.
- In the renal system, peritubular capillaries are tiny blood vessels, supplied by the efferent arteriole, that travel alongside nephrons allowing reabsorption and secretion between blood and the inner lumen of the nephron. Peritubular capillaries surround the proximal and distal tubules, as well as the loop of Henle, where they are known as vasa recta
- Macula densa cells- Juxtamedullary cells- a special type smooth muscle like cells- on the afferent arteriole cells Juxtamedullary cells- releases renin- into afferent arteriole then it goes through the efferent arterioles Trigger for release of renin -Low blood pressures in afferent arterioles is sensed by juxtamedullary cells and thus releases renin - sympathetic nerve endings on the juxtaglomerular cells - low sodium in distal convoluted tubules- this is sensed by the macula densa cells – this causes the macula densa to release hormone to justamedullary cells
- Amount Color Specific gravity pH Composition Nitrogenous wastes 1–2 liters per 24 hours; highly variable depending on fluid intake and water loss through the skin and GI tract Straw or amber; darker means more concentrated; should be clear, not cloudy 1.010–1.025; a measure of the dissolved material in urine; the lower the value, the more dilute the urine Average 6; range 4.6–8.0; diet has the greatest effect on urine pH 95% water; 5% salts and waste products Urea—from amino acid metabolism Creatinine—from muscle metabolism Uric acid—from nucleic acid metabolism
- The tubuloglomerular feedback mechanism: The juxtaglomerular complex consists of macula densa cells in the initial portion of the distal tubule and juxtaglomerular cells in the walls of the afferent and efferent arterioles. The macula densa is a specialized group of epithelial cells in the distal tubules that comes in close contact with the afferent and efferent arterioles. The macula densa cells contain the Golgi apparatus, which consists of intracellular secretory organelles directed toward the arterioles, suggesting that these cells may be secreting a substance toward the arterioles.
- This decrease in sodium chloride concentration initiates a signal from the macula densa that has two effects (Figure 27-11): (1) it decreases resistance to blood flow in the afferent arterioles, which raises glomerular hydrostatic pressure and helps return GFR toward normal; and (2) it increases renin release from the juxtaglomerular cells of the afferent and efferent arterioles, which are the major storage sites for renin. Renin released from these cells then functions as an enzyme to increase the formation of angiotensin I, which is converted to angiotensin II. Finally, angiotensin II constricts the efferent arterioles, thereby increasing glomerular hydrostatic pressure and helping return GFR toward normal.
- Nitrogenous wastes—as their name indicates, all of these wastes contain nitrogen. Urea is formed by liver cells when excess amino acids are deaminated to be used for energy production. Creatinine comes from the metabolism of creatine phosphate, an energy source in muscles. Uric acid comes from the metabolism of nucleic acids, that is, the breakdown of DNA and RNA. Although these are waste products, there is always a certain amount of each in the blood. Box 18–5: Blood Tests and Kidney Function describes the relationship between blood levels of these waste products and kidney function. Other non-nitrogenous waste products include small amounts of urobilin from the hemoglobin of old RBCs (see Fig. 11–4), and may include the metabolic products of medications. Table 18–3 summarizes the characteristics of urine. When a substance not normally found in urine does appear there, there is a reason for it. The reason may be quite specific or more general. Table 18–4 lists some abnormal constituents of urine and possible reasons for each (see also Box 18–6: Urinary Tract Infections).
- If the glomerular filtration rate declined by 50 % (e.g., because of a loss of one kidney) and the amount of K+ filtered across the glomerular kidney be able to maintain K+ balance? If so, how would this maintenance of K+ balance occur? If not, would the person become hyperkalamic? Normally, K+ excretion is determined primarily by the rate of K+ secretion by the late distal tubule and collecting duct and is largely independent of the GFR and the filtered load of K+. (1 mark) When 50% of the nephrons are lost, the late distal tubules and collecting ducts in the remaining functioning nephrons secrete more K+ so that K+ excretion and plasma [K+] are maintained at normal levels. (1 mark) However, if 80% to 85% of the nephrons are lost and GFR falls below 15% to 20% of normal. (1 mark) K+ secretion by the distal tubule and collecting duct cannot increase enough to maintain constant urinary K+ excretion. (1 mark) Hyperkalemia ensues. (1 mark)
- Na and Cl are reabsorbed by the thick ascending limb of the Henle loop. If a diuretic that inhibits NaCl reabsorption (e.g., furosemide) in the thick ascending limb was given to an individual, what would happen to water reabsorption by this segment? Furosemide would have no effect on water reabsorption in the thick ascending limb. (1 mark) Because, this segment of the nephron is relatively impermeable to water. (1 mark) Water is not reabsorbed even when NaCl reabsorption rates are high. (1 mark) Furosemide increases water excretion by reducing the osmolality of the medullary interstitial fluid, (1 mark) Which in turn reduces water reabsorption from the descending thin limb of Henle’s loop and medullary collecting duct. (1 mark)