The Urinary System
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| The Main Organs | 1. Two kidneys
2. Two ureters.
3. Urinary Bladder
4. Urethra.
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| Main Functions of the Kidneys | To filter blood plasma, separate wastes from the useful chemicals and eliminate
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| Main Functions of the Kidneys | Regulation of blood volume/pressure by eliminating or conserving water as necessary.
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| Main Functions of the Kidneys | Regulation of the osmolarity of body fluids by controlling the amounts of
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| Main Functions of the Kidneys | Secretion of the enzyme renin, which activates hormonal mechanisms that control BP
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| Main Functions of the Kidneys | Secretion of the hormone erythropoietin, which controls the RBC count and oxygen
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| Main Functions of the Kidneys | Function w/ the lungs to regulate the PCO2 and acid/base balance of the body fluids.
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| Main Functions of the Kidneys | Contribute to homeostasis of calcium by synthesizing calcitriol (Vitamin D).
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| Main Functions of the Kidneys | In times of starvation, to carry out gluconeogenesis: by deamination of amino acids
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| Nitrogenous Wastes | A waste is any substance that is useless to the body/present in excess of the body’s
needs. A metabolic waste is a waste substance produced by the body.
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| Urea | Constitutes about 50% of the nitrogenous waste.
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| Urea | It’s a by-product of protein catabolism. More specifically, proteins are degraded
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| Uric Acid | Produced by the catabolism of nucleic acids.
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| Creatinine | Produced by the catabolism of creatinine phosphate.
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| Blood Urea Nitrogen (BUN) | An expression used to indicate the level of nitrogenous waste in the blood.
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| Blood Urea Nitrogen (BUN) | The urea concentration is normally 10 to 20 mg/dl.
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| Blood Urea Nitrogen (BUN) | An abnormally elevated BUN is called azotemia - which may indicate renal
insufficiency.
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| Blood Urea Nitrogen (BUN) | Azotemia may progress to uremia – a syndrome of vomiting, diarrhea, dyspnea and
cardiac arrhythmia stemming from the toxic effects of nitrogenous wastes.
Convulsions, coma and death can follow w/in a few days.
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| The uremic patient has two options available: | a. Hemodialysis to remove the nitrogenous wastes from the blood.
b. A kidney transplant.
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| Gross Anatomy | Each kidney weighs about 160 g, measures 10 cm long, 5 cm wide, 2.5 cm thick.
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| Gross Anatomy | The lateral surface is convex and the medial surface is concave and has a slit called
the hilum, through which renal blood/lymphatic vessels, nerves and a ureter enters.
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| Gross Anatomy | The kidney is protected by three layers of connective tissue (CT)
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| Renal Fascia | This is a fibrous layer, immediately deep to the parietal peritoneum, that binds the
kidney and associated organs to the abdominal wall.
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| Renal Fascia | The renal fascia is fused w/ the peritoneum ventrally and w/ the deep fascia of the
lumbar muscles dorsally. Thus the kidneys are suspended in place.
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| Adipose Capsule | This is a layer of fat that cushions the kidney and holds it in place.
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| Renal Capsule | This is a fibrous sac that encloses the kidney. Collagen fibers extend from the renal
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| The renal parenchyma | This is the glandular tissue that forms the urine.
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| The renal parenchyma | It encircles a medial space called the renal sinus. This sinus is occupied by
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| Renal Cortex | This is the outer part, about 1 cm thick.
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| Renal Medulla | This is the inner part.
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| Circulation | The kidneys only account for 0.4% of the body weight but receive 21% of the cardiac
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| Circulation | Each kidney is supplied by a renal artery arising from the aorta
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| The Nephron | Each kidney contains about 1.2 million functional units called nephrons.
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| nephron has two main parts | Renal Corpuscle & Renal Tubule
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| Renal Corpuscle | This is the place wherein filtration of blood plasma occurs.
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| Renal Tubule | This structure processes the filtrate into urine.
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| The renal corpuscle consists of two structures | Glomerulus & Glomerular Filtrate
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| Glomerular (Bowman’s) Capsule | This capsule has two layers:
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| Parietal(outer) Layer | Composed of simple squamous epithelium.
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| Visceral (inner) Layer | Composed of cells called podocytes that wrap around capillaries of glomerulus.
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| Glomerular Filtrate | This is the fluid that filters from the glomerular capillaries
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| Glomerular Filtrate | This filtrate collects in the capsular space (b/w the parietal/visceral layers), then
flows into the renal tubule.
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| The renal corpuscle has two poles | Vascular Pole & Urinary Pole
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| Vascular Pole | The place where the afferent arteriole enters the capsule, bringing blood to the
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| Urinary Pole | This is the place where the parietal wall of the capsule gives rise to the renal tubule.
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| The Renal Tubule | The renal tubule is a duct that leads away from the glomerular capsule and ends at the
tip of a medullary pyramid.
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| The Renal Tubule | The renal tubule is divided into four major areas
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| Proximal Convoluted Tubule (PCT) | a. This arises from the glomerular capsule.
b. Its made of simple cuboidal epithelium w/ prominent microvilli that assist in the
absorption.
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| Nephron Loop | The PCT straightens out to form the long U shaped nephron loop (Loop of Henle) and has 2 limbs
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| Descending Limb | This is the first part of the loop that passes from the cortex into the medulla.
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| Ascending Limb | The part of the loop (in the medulla) that turns upward/returns to the cortex.
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| Thick Segments | These segments have simple cuboidal epithelium. They form the initial part of
the descending limb and part or all of the ascending limb. Cells here are
heavily involved in active transport of salts – so they have high metabolic
activity.
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| Thin Segments | This segment has simple squamous epithelium. It forms the lower part of the
descending limb and may continue in part of the ascending limb. The cells
here have low metabolic activity and are very permeable to water.
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| Distal Convoluted Tubule (DCT) | a. This tubule is formed when the ascending limb of the nephron returns to the
cortex.
b. This tubule is shorter/less convoluted than the PCT.
c. Composed of cuboidal epithelium w/ smooth cells nearly devoid of microvilli.
d. The DCT is the end of the
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| Collecting Duct | a. The DCTs of several nephrons drain into a straight tubule called the collecting
duct which passes down into the medulla.
b. Near the papilla, several collecting ducts merge to form a large papillary duct.
About 30 of these drain from each papilla in
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| Collecting Duct | Collecting and Papillary Ducts are line w/ simple cuboidal epithelium.
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| The pathway of the flow of urine from formation of glomerular filtrate to voiding: | Glomerular capsule -- PCT --- nephron loop --- DCT ----- Collecting duct
---- Papillary Duct-----Minor Calyx --- Major Calyx --- Renal Pelvis
------ Ureter ------Urinary Bladder ----- Urethra.
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| The kidney converts blood plasma into urine in three stages | a)Glomerular Filtration
b)Tubular Reabsorption and Secretion
c)Water Conservation
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| The Filtration Membrane | Glomerular filtration is a specialized case of the capillary fluid exchange process - a
process in which water and some solutes in the blood plasma pass from the capillaries
of the glomerulus into the capsular space of the nephron.
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| The Fenestrated Endothelium of the Capillary | Endothelial cells of the glomerular capillaries are fenestrated w/ large filtration pores
about 70 to 90 nm in diameter. These pores are highly permeable, although their pores
are small enough to exclude blood cells from the filtrate.
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| The Basement Membrane | i)This membrane consists of a proteoglycan gel.
ii)This membrane excludes (does not allow to pass) molecules > 8 nm. Some smaller
molecules are also excluded by a negative electrical charge on the proteoglycan.
Example
Blood albumin is < 7 nm but its
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| Filtration Slits | The podocyte of the glomerular capsule has extensions called pedicles that wrap around
the capillaries. These processes have negatively charged filtration slits about 30 nm b/w
them, which are an additional obstacle to large anions.
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| Passage of molecules through the filtration membrane (FM) | a)Most molecules smaller than 3 nm can pass freely through the filtration membrane into
the capsular space. This includes water, electrolytes, glucose, fatty acids, amino acids,
nitrogenous wastes and vitamins.
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| Passage of molecules through the filtration membrane (FM) | b)Some molecules of low MW are retained in the blood because they are bound to
plasma proteins that can’t pass through the membrane.Example
Most calcium, iron and thyroid hormone in the blood are bound to plasma proteins that
retard their filtration by
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| Kidney infections/trauma can damage the FM | can damage the FM and allow albumin or blood cells to
filter through. Therefore, kidney disease may be marked by proteinuria (presence of
protein, especially albumin in the urine) or hematuria (blood in the urine).
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| Filtration Pressure | Glomerular filtration follows the same principles that dictate filtration in other blood
capillaries but there are important differences in the magnitude of the forces involved:
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| Filtration Pressure | a)The blood hydrostatic pressure (BHP) is much higher in the glomerulus than elsewhere
– about 60 mm Hg compared w/ 10 to 15 mm Hg in most other capillaries. This results
from the fact that the afferent arteriole is much larger than the efferent arterio
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| Filtration Pressure | b)The hydrostatic pressure in the capillary space is about 18 mm Hg, compared w/ the
slightly negative interstitial pressures elsewhere. This results from the high rate of
filtration occurring here and the continual accumulation of fluid in the capsule.
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| Filtration Pressure | c)The colloid osmotic pressure (COP) in the blood is about the same here as anywhere
else, 32 mm Hg.
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| Filtration Pressure | d)The glomerular filtrate is nearly protein free and has no significant COP.
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| Filtration Pressure | Therefore, there is a high outward pressure of 60 mm Hg, opposed by two inward
pressures of 18 and 32 mm Hg, giving a net filtration pressure (NFP) of
60out - 18in - 32in = 10 mm Hgout
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| Glomerular Filtration Rate | Glomerular filtration rate (GFR) is the amount of filtrate formed per minute by the
two kidneys combined.
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| Glomerular Filtration Rate | This is a rate of about 180 L/day in males
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| Glomerular Filtration Rate | 150 L/day in females
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| Glomerular Filtration Rate | An average adult reabsorbs 99% of the filtrate into the blood and excretes 1 to 2 L of urine/day.
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| Regulation of Glomerular Filtration | GFR must be precisely controlled.The only way to regulate GFR from moment to moment is to change glomerular BP,
which is achieved by three homeostatic mechanisms: renal autoregulation,
sympathetic control and hormonal control.
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| Renal Autoregulation | Renal autoregulation is the ability of the nephrons to adjust their own blood flow/GFR
w/out external (nervous or hormonal) control.
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| The Myogenic Mechanism | a. stabilizing GFR based on the tendency of smooth muscle to contract when stretched.
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| The Myogenic Mechanism | b. When arterial BP rises, it stretches the afferent arteriole. The arteriole contracts
and thus prevents blood flow into the glomerulus from dramatically changing.
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| Tuboglomerular Feedback | In this mechanisms, the juxtaglomerular apparatus (JGA) monitors fluid entering
the DCT and adjusts the GFR to maintain homeostasis.
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| Juxtaglomerular Cells (JG cells) | (a) enlarged smooth muscle cells found in afferent arteriole/to some extent in the efferent arteriole.
(b) When stimulated by the macula dense, the JG cells dilate or constrict
(c) These JG cells contain granules of renin,
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| The Macula Densa | This is a patch of slender, closely spaced epithelial cells at the start of the
DCT, directly across from the JG cells.
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| Mesangial Cells | (a) These cells are found in the cleft b/w the afferent and efferent arterioles
and among capillaries in the glomerulus.
(b) They are connected to the macula densa and JG cells by gap junxtions and
may mediate communication b/w those cells.
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| Sympathetic Control | a)Sympathetic nerve fibers heavily innervate the renal blood vessels.
b)In strenuous exercise or acute conditions like circulatory shock, the sympathetic
nervous system and adrenal epinephrine constrict the afferent arterioles.
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| Sympathetic Control | i)This reduces GFR and urine production.
ii)It also redirects blood from the kidneys to the heart, brain and skeletal muscles
where its more urgently needed.
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| Hormonal Control: The Renin-Angiotensin Mechanism | a)When BP decreases, the sympathetic nerves also stimulate the JG cells to secrete the
enzyme renin.
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| Mechanism of Conversion of Renin to Angiotensin II | i)Renin converts a plasma protein angiotensinogen to angiotensin I.
ii)In the lungs, angiotensin converting enzyme (ACE), converts angiotensin I to
angiotensin II.
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| Physiological effects of Angiotensin II | i)Stimulates widespread vasoconstriction, which increases MAP throughout the body.
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| Physiological effects of Angiotensin II | ii)Constricts both afferent/efferent arterioles – which has a net effect of decreasing
GFR/water loss.
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| Physiological effects of Angiotensin II | iii)Stimulates NaCl/water reabsorption by the PCT.
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| Physiological effects of Angiotensin II | iv)Stimulates the adrenal cortex to secrete aldosterone, which in turn promotes
sodium/water retention by the DCT/collecting duct.
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| Physiological effects of Angiotensin II | v)Stimulates secretion of antidiuretic hormone (ADH) which promotes water
reabsorption.
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| Physiological effects of Angiotensin II | vi)Stimulates the sense of thirst and encourages water intake.
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| Sodium | i)Sodium reabsorption is key to everything else because it creates an osmotic/electrical
gradient that drives the reabsorption of water/other solutes.
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| Sodium | Sodium is the most abundant cation in the glomerular filtrate – and is reabsorbed by
both trancellular and paracellular routes.
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| Chloride | Chloride is reabsorbed through both the transcellular/paracellular routes.
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| Chloride reabsorption is favored by two factors | Negative chloride ions tend to follow the positive Na+ ions by electrical
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| Glucose | Glucose is cotransported w/ Na+ by carriers called sodium glucose transport proteins.
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| Glucose | Glucose is then removed from the basolateral surface of the cell by facilitated
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| Glucose | Normally all glucose in the tubular fluid is reabsorbed and there is none in the urine.
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| The Myogenic Mechanism | Conversely, when BP decreases, the afferent arteriole relaxes and allows blood to
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| Tubular Reabsorption and Secretion | Conversion of the glomerular filtate to urine involves the removal and addition of
chemicals by tubular reabsorption and secretion.
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| Proximal Convoluted Tubule | The PCT reabsorbs about 65% of the glomerular filtrate, while it also removes
substances from the blood and secretes them into the tubule for disposal in the urine.
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| Tubular Reabsorption | i)This is the process of reclaiming water/solutes from the tubular fluid and returning
them to the blood. The PCT reabsorbs a greater variety of chemicals than any other
part of the nephron.
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| Transcellular Route | Substances pass through the cytoplasm and out the base of the epithelial cells.
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| Paracellular Route | 1. Here substances pass b/w the epithelial cells.
2. The “tight” junctions b/w the epithelial cells are quite leaky and allow for
water, minerals, urea, etc. to pass b/w the cells.
3. Substances that pass enter the ECF and are taken up by the peritubul
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| Nitrogenous Wastes | Urea diffuses through the tubule epithelium with water.The nephron reabsorbs 40 to 60% of the urea in the tubular fluid – but since it
reabsorbs 99% of the water, urine has a much higher urea concentration than blood
or glomerular filtrate.kidney
remov
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| Nitrogenous Wastes | The PCT reabsorbs nearly all the uric acid entering it but later parts of the nephron
secrete it back into the tubular fluid.
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| Nitrogenous Wastes | Creatinine is not reabsorbed. It is too large to diffuse through water channels in the
plasma membrane and there are no transport proteins for it. Therefore all creatinine
filtered by the glomerulus is excreted in the urine.
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| Water | i)The kidneys reduce about 180 L of glomerular filtrate to 1 to 2 L of urine/day – so
clearly water reabsorption is an important function.
ii)About two thirds of the water is reabsorbed by the PCTiii)of water reabsorption is regulated by
hormones accor
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| Tubular Secretion | Tubular secretion is a process in which the renal tubule extracts chemicals from the
capillary blood and secretes them into the tubular fluid.
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| Tubular Secretion | Tubular secretion in the PCT/nephron loop serves two purposes:
Waste Removal
Acid-base Balance
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| Waste Removal | a. Urea, uric acid, bile salts, ammonia, catecholamines, prostaglandins and some
creatinine are secreted into the tubule. Tubular secretion of uric acid
compensates for its earlier reabsorption in the PCT and accounts for all the uric
acid in the urine
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| Acid-base Balance | Tubular secretion of H+/ HCO3- ions serves to regulate the pH of body fluids.
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| The Nephron Loop | 1. The main function of the nephron loop is to produce a salinity gradient that enables
the collecting duct to concentrate the urine and conserve water.
2. In addition, the nephron loop reabsorbs about 25% of the Na+, K+ and Cl- and 15%
of the water in
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| The Distal Convoluted Tubule and Collecting Duct | a)Fluid arriving in the DCT still contains about 20% of the water and 7% of the salts
from the glomerular filtrate. If this were all passed as urine, it would amount to 36
L/day – therefore a great deal of fluid reabsorption must still occur.
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| The Distal Convoluted Tubule and Collecting Duct | b)The DCT and collecting duct reabsorb variable amounts of water/salts and are
regulated by several hormones – most importantly: aldosterone, atrial natriuretic peptide,
antidiuretic hormone and parathyroid hormone.
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| Principal Cells | a. These are the most abundant.
b. They have receptors for the hormones mentioned.
c. These cells are mainly involved in salt/water balance.
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| Intercalated Cells | a. These are fewer in number.
b. They have a high number of mitochondria, reabsorb K+, secrete H+ into the
tubule lumen.
c. Primarily involved in acid-base balance.
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| Aldosterone | a)This is a steroid hormone secreted by the adrenal cortex under the following
conditions:
i)When the blood Na+ concentration falls
ii)Increase blood K+ concentration
iii)Decrease in BP. Initially a decrease in BP stimulates the kidney to secrete reni
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| Atrial Natriuretic Peptide (ANP) | a)This hormone is secreted by the atrial myocardium of the heart in response to high BP.i)It dilates the afferent arteriole and constricts the efferent arteriole, thus increasing the
glomerular filtration rate.iii)It inhibits the secretion of ADH and the
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| Antidiuretic Hormone | a)ADH is secreted by the posterior lobe of the pituitary gland in response to dehydration
and increasing blood osmolarity.
b)In short, it makes the collecting duct more permeable to water, so water in the tubular
fluid reenters the tissue fluid and blo
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| Parathyroid Hormone | a)A calcium deficiency stimulates the parathyroid glands to secrete PTH – which acts in
several ways to restore calcium homeostasis.
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