The Urinary System Part 1

The Urinary System Part A

Objectives Components of the Urinary System Identification of various parts of urinary system Functions of the urinary system Describe the structure of Nephron Explain the process involved in formation of urine Composition of urine GFR Formation of Diluted and Concentrated Urine Explain how water and electrolyte balance is maintained

Components of the Urinary System

Urinary system is the main excretory system & consists of following structures 2 Kidneys, that form and secrete urine 2 Ureters, which take urine from kidneys to urinary bladder Urinary Bladder: Collection and Temporary storage site of urine Urethra: Help discharging urine from bladder to exterior.

Components of the Urinary System

Components of the Urinary System

Kidney Functions Filter 200 liters of blood daily, allowing toxins, metabolic wastes, and excess ions to leave the body in urine Kidneys produce urine Metabolic Wastes products Nitrogenous compounds Urea and Uric acid Excess ions and other subs e.g. Drugs

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Excretion of metabolic waste products and foreign chemicals

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Regulation of water and electrolyte balances

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Regulation of body fluid osmolality and electrolyte concentrations

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Regulation of arterial pressure

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Regulation of acid-base balance

Other Renal Functions

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Secretion,metabolism,and excretion of hormones

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Gluconeogenesis during prolonged fasting

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Production of rennin to help regulate blood pressure

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Production of erythropoietin to stimulate RBC production

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Activation of vitamin D

Urinary System Organs

Kidney Location and External Anatomy The bean-shaped kidneys lie in a retroperitoneal (behind peritoneum) position in the superior lumbar region and extend from the twelfth (12th) thoracic to the third (3rd) lumbar vertebrae. i.e T12 to L3 An adult’s kidney has a mass of about 150 g (5 ounces) and its average dimensions are 12 cm long, 6 cm wide, and 3 cm thick. The right kidney is lower than the left because it is crowded by the liver. The lateral surface is convex and the medial surface is concave, with a vertical cleft called the renal hilus leading to internal space within the kidney called the renal sinus. Ureters, renal blood vessels, lymphatics, and nerves enter and exit at the hilus and occupy sinus.

Kidney Location and External Anatomy

Layers of Tissue Supporting the Kidney

Renal capsule:– Transparent capsule that prevents infections in surrounding regions from spreading to the kidneys

Adipose capsule:– Fatty mass that cushions the kidney against blows and helps attach it to the body wall

Renal fascia:– Outer layer of dense fibrous connective tissue that anchors the kidney

Kidney Location and External Anatomy

Figure 25.2a

Internal Anatomy A frontal section shows three distinct regions Cortex – the light colored, granular superficial region Medulla – exhibits cone-shaped medullary (renal) pyramids Pyramids are made up of parallel bundles of urine-collecting tubules Broad Base of collecting tubules is towards Cortex and apex or papilla (nipple) points towards pelvis Pyramids are separated by Renal columns which are inward extensions of cortical tissue The medullary pyramid and its surrounding capsule constitute a lobe (approximate 8 lobes in one kidney)

Internal Anatomy

Renal pelvis –flat, funnel-shaped tube is continuous with the ureter leaving the hilus

Major calyces – Branching extensions of the pelvis form two or three major calyces (singular: calyx), each of which subdivides to form several minor calyces, cup-shaped areas that enclose the papillae. Function: Collect urine draining from papillae Empty urine into the pelvis

Urine flows through the pelvis and ureters to the bladder

Internal Anatomy

Blood and Nerve Supply

Approximately one-fourth (25%) (1200 ml) of systemic cardiac output flows through the kidneys each minute Arterial flow into and venous flow out of the kidneys follow similar paths The nerve supply is via the renal plexus

The Nephron Nephrons are the structural and functional units that form urine, (over 1 million / kidney). No Regeneration of new nephrons. 1 % loss every year after 40 years of age. Nephrons consist of: Glomerulus – a bunch of capillaries associated with a renal tubule (200 micrometer in diameter) Glomerular or Bowman’s capsule – blind, cup-shaped end of a renal tubule that completely surrounds the glomerulus Renal corpuscle1 / Malpighian body – the glomerulus and its Bowman’s capsule (Marcello Malpighi)

The Nephron

The Nephron

Anatomy of the Glomerular Capsule

The external parietal layer is a simple squamous epithelium, simply a structural layer. The visceral layer consists of highly modified, branching epithelial cells called podocytes. Extensions of the octopus-like podocytes terminate in foot processes Filtration slits – (5-25 nm) openings between the foot processes that allow filtrate to pass into the capsular space

Renal Tubule The remainder of Nephron is almos 3cm long (1.2 inch) and has 3 major parts Proximal convoluted tubule (PCT) Loop of Henle Distal convoluted tubule (DCT)

Proximal convoluted tubule (PCT) composed of cuboidal cells with numerous microvilli and mitochondria, this brush border dramatically increases the surface area and capacity for reabsorbing water and solutes from the filtrate and secreting substances into filterate.

Renal Tubule

Loop of Henle – a hairpin-shaped loop of the renal tubule Proximal part is similar to the proximal convoluted tubule Proximal part is followed by the thin segment (simple squamous epithelium) freely permeable to water and the thick segment (cuboidal to columnar cells)

Distal convoluted tubule (DCT) – cuboidal cells without microvilli that function more in secretion than reabsorption

Connecting Tubules The distal portion of the distal convoluted tubule nearer to the collecting ducts Two important cell types are found here Intercalated cells Cuboidal cells with microvilli Function in maintaining the acid-base balance of the body

Principal cells Cuboidal cells without microvilli Help maintain the body’s water and salt balance

Renal Tubule

Nephrons

Cortical nephrons – 85% of nephrons; located in the cortex Juxtamedullary nephrons: (Juxta  Near) Are located at the cortex-medulla junction Have loops of Henle that deeply invade the medulla Have extensive thin segments Are involved in the production of concentrated urine

Nephrons

Nephrons (scanning Electron Microscopic picture, 90x)

Capillary Beds of the Nephron

Every nephron has two capillary beds Glomerulus Peritubular capillaries

Each glomerulus is: Fed by an afferent arteriole Drained by an efferent arteriole

Capillary Beds of the Nephron

Blood pressure in the glomerulus is high because: Arterioles are high-resistance vessels Afferent arterioles have larger diameters than efferent arterioles

Fluids and solutes are forced out of the blood throughout the entire length of the glomerulus

Capillary Beds of the Nephron

Peritubular beds are low-pressure, porous capillaries adapted for absorption that: Arise from efferent arterioles Cling to adjacent renal tubules Empty into the renal venous system

Vasa recta – long, straight efferent arterioles of juxtamedullary nephrons

Capillary Beds

Vascular Resistance in Microcirculation

Afferent and efferent arterioles offer high resistance to blood flow Blood pressure declines from 95mm Hg in renal arteries to 8 mm Hg in renal veins

Vascular Resistance in Microcirculation

Resistance in afferent arterioles: Protects glomeruli from fluctuations in systemic blood pressure

Resistance in efferent arterioles: Maintains high glomerular pressure Reduces hydrostatic pressure in peritubular capillaries

Structural Details of Glomerulus Glumerular capillaries are supplied by an afferent arteriole and drained by a slightly smaller efferent arteriole Three cellular layers separate blood from the glomerular filtrate in Bowman's capsule: Inner Capillary endothelium (70-90 nm pores) Middle basal lamina.((250-350 nm thick) (No visible gaps or pores) rich in negatively charged glycosaminoglycans such as heparan sulfate.

Outer Specialized epithelium of the capsule made up of podocytes cover the glomerular capillaries. (5-25nm pores)

Mesangial cells are found in the interstitial space between endothelial cells of the glomerulus . The mesangial cells are contractile and play a role in the regulation of glomerular filtration Glomerular capillary endothelium – fenestrated epithelium that allows solute-rich, virtually protein-free filtrate to pass from the blood into the glomerular capsule

Structural Details of Glomerulus

Structural Details of Glomerulus

Structural Details of Glomerulus

Scheme of filtration barrier (blood-urine) in the kidney. B. The endothelial cells of the glomerulus; 1. pore (fenestra). C. B. Glomerular basement membrane: 1. lamina rara externa 2. lamina densa 3. lamina rara interna D. Podocytes: 1. enzymatic and structural protein 2. filtration slit 3. diaphragma

Juxtaglomerular Apparatus (JGA)

Where the distal tubule lies against the afferent (sometimes efferent) arteriole Arteriole walls have juxtaglomerular (JG) cells Enlarged, smooth muscle cells Have secretory granules containing renin Act as mechanoreceptors

Juxtaglomerular Apparatus (JGA)

Macula densa (dense spot) Tall, closely packed cells of distal convoluted tubule Lie adjacent to JG cells Function as chemoreceptors or osmoreceptors Respond to changes in NaCl content of filterate

Mesanglial cells: Have phagocytic and contractile properties Influence capillary filtration PLAY

Urinary System: Anatomy Review

Juxtaglomerular Apparatus (JGA)

Filtration Membrane

Filter that lies between the blood and the interior of the glomerular capsule It is composed of three layers Fenestrated endothelium of the glomerular capillaries Visceral membrane of the glomerular capsule (podocytes) Basement membrane composed of fused basal laminae of the other layers

Filtration Membrane

Filtration Membrane (scanning Electron Microscopic picture, 3000x)

Filtration Membrane

Mechanisms of Urine Formation Kidney blood Supply = 1200ml /min Approx 650 ml is plasma, out of which 1/5th or 100-125ml is forced in the renal tubules. So The kidneys filter the body’s entire plasma volume 60 times each day The filtrate: The filtrate contains all plasma components except protein The filtrate loses water, nutrients, and essential ions to become urine

The urine contains metabolic wastes and unneeded substances

Mechanisms of Urine Formation

Urine formation and adjustment of blood composition involves three (3) major processes Glomerular filtration Tubular reabsorption Secretion

1- Glomerular Filtration Glomerular filtration is a passive process in which hydrostatic pressure forces fluids and solutes through a membrane. Filtration does not consume metabolic energy, so Glomeruli act as simple mechanical filters The glomerulus is more efficient than other capillary beds because of following: Filtration membrane significantly more permeable to water and solutes Posses a large surface area

High Glomerular blood pressure Approx. 55 mm Hg as compared to 18 mm Hg or less in other capillary beds

It has a higher net filtration pressure

Plasma proteins are not filtered and are used to maintain oncotic pressure 1 of the blood

Net Filtration Pressure (NFP) The pressure responsible for filtrate formation NFP, responsible for filtrate formation, involves forces acting at the glomerular bed. Glomerular hydrostatic pressure (HPg) (The glomerular blood pressure) is the chief force pushing water and solutes out of the blood and across the filtration membrane. The HPg is opposed by two forces that inhibit fluid loss from glomerular capillaries. These filtration-opposing forces are colloid osmotic (oncotic) pressure of glomerular blood (OPg) capsular hydrostatic pressure (HPc) exerted by fluids in the glomerular capsule.

NFP = HPg – (OPg + HPc)

Glomerular Filtration Rate (GFR)

The total amount of filtrate formed per minute by the kidneys Factors governing filtration rate at the capillary bed are: Total surface area available for filtration Filtration membrane permeability Net filtration pressure

Glomerular Filtration Rate (GFR)

In adults the normal GFR in both kidneys is 120– 125 ml/min. Huge amounts of filtrate can be produced due to large surface area and greater permeability, even with the usual modest NFP of 10 mm Hg. A drop in glomerular pressure of only 18% stops filtration altogether. GFR is directly proportional to the NFP Changes in GFR normally result from changes in glomerular blood pressure

Glomerular Filtration Rate (GFR)

Regulation of Glomerular Filtration

If the GFR is too high: Needed substances cannot be reabsorbed quickly enough and are lost in the urine

If the GFR is too low: Everything is reabsorbed, including wastes that are normally disposed of

Regulation of Glomerular Filtration GFR is regulated by Two controls Intrinsic Controls (Renal autoregulation) Extrinsic controls

These two types of controls serve two different (and sometimes opposing) needs. The kidneys need Constant GFR. Body Needs  Constant Blood Volume Constant B.P

Intrinsic controls Act locally within the kidney to maintain GFR

The extrinsic controls Act by the nervous and endocrine systems to maintain blood pressure.

In extreme changes of blood pressure (mean arterial pressure less than 80 or greater than 180 mm Hg), extrinsic controls take priority over intrinsic controls.

Intrinsic Controls (Autoregulation)

The kidney can maintain a nearly constant GFR despite fluctuations in systemic arterial blood pressure by adjusting its own resistance to blood flow , by a process called renal autoregulation Renal autoregulation involves two types of controls:  Myogenic mechanism  Tubuloglomerular feedback mechanism

Myogenic mechanism

It is based on the tendency of vascular smooth muscle to contract when stretched1. Increasing systemic blood pressure causes the afferent arterioles to constrict, which restricts blood flow into the glomerulus and prevents glomerular blood pressure from rising to damaging levels. Declining systemic blood pressure causes dilation of afferent arterioles and raises glomerular hydrostatic pressure. Both responses help maintain a normal GFR

Myogenic mechanism

Tubuloglomerular feedback mechanism This feedback mechanism is “directed” by the macula densa cells of the juxtaglomerular apparatus. These cells respond to filtrate NaCl concentration (which varies directly with filtrate flow rate). GFR, time for reabsorption so filtrate.

concentration of NaCl in the

Macula densa cells release vasoconstrictor chemical (probably ATP) that causes intense constriction of the afferent arteriole. blood flow into the glomerulus, which the NFP and GFR, time for filtrate processing (NaCl absorption). slowly flowing low NaCl concentration, ATP release inhibited,  vasodilation of the afferent arterioles. so flow into the glomerulus, thus in the NFP and GFR.

blood to

Tubuloglomerular feedback mechanism

Limitations of Intrinsic control mechanisms

Maintain constant blood flow through the kidneys over a range of about 80 to 180 mm Hg. However, the intrinsic controls cannot handle extremely low systemic blood pressure, e.g that might result from serious hemorrhage. Once the mean systemic blood pressure drops below 80 mm Hg, autoregulation stops.

Extrinsic Controls

The purpose of the extrinsic controls regulating the GFR is to maintain systemic blood pressure. Which is sometimes harmful to kidneys. Two control mechanisms involved Neural Mechanism Neural renal controls serve the needs of the body as a whole

Hormonal Mechanism

Neural (Sympathetic NS) Mechanism When the sympathetic nervous system is at rest: Renal blood vessels are maximally dilated Autoregulation mechanisms continue to regulate blood flow

Under stress: Norepinephrine is released by the sympathetic nervous system Epinephrine is released by the adrenal medulla These substances act on alpha-adrenergic receptors on vascular smooth muscle, inhibiting filtrate formation by strongly constricting afferent arterioles.

Indirect activation of the renin - angiotensin mechanism by stimulating the macula densa cells. ( Filtrate) The sympathetic nervous system also directly stimulates the granular cells to release renin.

Hormonal (Renin-Angiotensin) Mechanism Is triggered when the granular cells release renin Renin acts enzymatically on angiotensinogen (a plasma globulin made by the liver) to convert angiotensin I Angiotensin I is converted to angiotensin II by angiotensin converting enzyme (ACE) associated with capillary endothelium in various body tissues, especially lungs. Angiotensin II acts in five ways to stabilize systemic blood pressure and extracellular fluid volume.  As a potent vasoconstrictor, it activates smooth muscle of arterioles throughout the body, raising mean arterial blood pressure.

Angiotensin II actions

1. It stimulates reabsorption of sodium, both directly by acting on renal tubules and indirectly by triggering the release of aldosterone from the adrenal cortex. water follows sodium osmotically, blood volume and blood pressure rise. 2. It stimulates the hypothalamus to release ADH hormone and activates the hypothalamic thirst center, both of which increase blood volume. 3. It also increases fluid reabsorption by decreasing peritubular capillary hydrostatic pressure by efferent arterioles constriction 4. Finally,it targets the mesangial cells, that contract and reduce the GFR by decreasing the total surface area of glomerular capillaries available for filtration.

Renin Release

Renin release is triggered by: Reduced stretch of the granular cells. A drop in mean systemic blood pressure below 80 mm Hg (hemorrhage, dehydration, etc.) reduces the stretch of the granular cells and stimulates them to release more renin

Stimulation of the granular cells by activated macula densa cells to releases renin, this signal may be Increased release of PGE2 (Vasodilator) Decreased release of ATP (Vasoconstrictor) or both

Direct stimulation of the Granular cells via β1-adrenergic receptors by renal nerves

Other Factors Affecting Glomerular Filtration Prostaglandins (PGE2 and PGI2) Vasodilators produced in response to sympathetic stimulation and angiotensin II to counteract over vasoconstriction. Are thought to prevent renal damage when peripheral resistance is increased

Nitric oxide – vasodilator produced by the vascular endothelium Adenosine – vasoconstrictor of renal vasculature Endothelin – a powerful vasoconstrictor secreted by tubule cells Urinary System: Glomerular Filtration PLAY Intrarenal angiotensin II  Vasoconstrictor