Urinary system

Functions of the Kidneys

Filter blood and excrete toxic metabolic wastes.
Regulate blood volume, pressure, and osmolarity.
Regulate electrolytes and acid-base balance.
Secrete erythropoietin, which stimulates the production of red blood cells.
Help regulate calcium levels by participating in calcitriol synthesis.
Clear hormones from blood.
Detoxify free radicals.
In starvation, they synthesize glucose from amino acids.

Waste

any substance that is useless to the body or present in excess of the body's needs

Metabolic waste

waste substance produced by the body

Urea formation

Proteins → amino acids → NH2 removed → forms ammonia, liver converts ammonia to urea

Uric acid

product of nucleic acid catabolism

Creatinine

product of creatine phosphate catabolism

Blood urea nitrogen (BUN)

level of nitrogenous waste in blood
Normal concentration of blood urea is 10 to 20 mg/dL

Azotemia

elevated BUN; may indicate renal insufficiency

Uremia

syndrome of diarrhea, vomiting, dyspnea, and cardiac arrhythmia stemming from the toxicity of nitrogenous waste; treatment is hemodialysis or organ transplant

Excretion

separating wastes from body fluids and eliminating them.
Four body systems carry out excretion.
• Respiratory system—CO2, small amounts of other gases, and water.
• Integumentary system—water, inorganic salts, lactic acid, urea in sweat.
• Digestive system—water, salts, CO2, lipids, bile pigments, cholesterol, and other metabolic waste.
• Urinary system—many metabolic wastes, toxins, drugs, hormones, salts, H+, and water.

Kidney Position

• Lie against posterior abdominal wall at level of T12 to L3.
• Right kidney is slightly lower due to large right lobe of liver.
• Rib 12 crosses the middle of the left kidney.
• Retroperitoneal along with ureters, urinary bladder, renal artery and vein, and adrenal glands.

Renal parenchyma

glandular tissue that forms urine.
• Appears C-shaped in frontal section.
• Encircles renal sinus.

Renal sinus

cavity that contains blood and lymphatic vessels, nerves, and urine-collecting structures.
• Adipose fills the remaining cavity and holds structures in place.

Two zones of renal parenchyma

• Outer renal cortex.
• Inner renal medulla

Renal columns

extensions of the cortex that project inward toward sinus

Renal pyramids

6 to 10 with broad base facing cortex and renal papilla facing sinus

Lobe of kidney

one pyramid and its overlying cortex

Minor calyx

cup that nestles the papilla of each pyramid; collects its urine

Major calyces

formed by convergence of 2 or 3 minor calyces

Renal pelvis

formed by convergence of 2 or 3 major calyces

Ureter

a tubular continuation of the pelvis that drains urine down to the urinary bladder

Renal Circulation

Kidneys are only 0.4% of body weight but receive about 21% of cardiac output (renal fraction).
Renal circulation:
• Renal artery divides into segmental arteries that give rise to:
• Interlobar arteries: up renal columns, between pyramids.
• Arcuate arteries: over pyramids.•
Cortical radiate arteries: up into cortex.
• Branch into afferent arterioles: each supplying one nephron.
•Leads to a ball of capillaries—glomerulus
• Blood is drained from the glomerulus by efferent arterioles.
• Most efferent arterioles lead to peritubular capillaries.
• Some efferents lead to vasa recta—a network of blood vessels within renal medulla.
• Capillaries then lead to cortical radiate veins or directly into arcuate veins.
• Arcuate veins lead to interlobar veins which lead to the renal vein.
• Renal vein empties into inferior vena cava.
In the cortex, peritubular capillaries branch off of the efferent arterioles supplying the tissue near the glomerulus, the proximal and distal convoluted tubules.
In the medulla, the efferent arterioles give rise to the vasa recta, supplying the nephron loop (loop of Henle) portion of the nephron.

The Nephron

Each kidney has about 1.2 million nephrons.
Each composed of two principal parts.
• Renal corpuscle: filters the blood plasma.
• Renal tubule: long, coiled tube that converts the filtrate into urine.
Renal corpuscle consists of the glomerulus and a two-layered glomerular (Bowman) capsule that encloses glomerulus.
• Parietal (outer) layer of glomerular capsule is simple squamous epithelium.
• Visceral (inner) layer of glomerular capsule consists of elaborate cells called podocytes that wrap around the capillaries of the glomerulus.
• Capsular space separates the two layers of glomerular capsule.

Renal (uriniferous) tubule

duct leading away from the glomerular capsule and ending at the tip of the medullary pyramid.
Divided into four regions.
• Proximal convoluted tubule, nephron loop (loop of Henle), distal convoluted tubule: parts of one nephron.
• Collecting duct receives fluid from many nephrons.

Proximal convoluted tubule (PCT)

arises from glomerular capsule.
• Longest and most coiled region.
• Simple cuboidal epithelium with prominent microvilli for majority of absorption.

Nephron loop (loop of Henle)

is long U-shaped portion of renal tubule.
• Descending limb and ascending limb.
• Thick segments have simple cuboidal epithelium.
• Initial part of descending limb and part or all of ascending limb; heavily engaged in the active transport of salts and have many mitochondria.
• Thin segment has simple squamous epithelium.
• Forms lower part of descending limb; cells very permeable to water.

Distal convoluted tubule (DCT)

begins shortly after the ascending limb reenters the cortex.
• Shorter and less coiled than PCT; cuboidal epithelium without microvilli; DCT is the end of the nephron

Collecting duct

receives fluid from the DCTs of several nephrons as it passes back into the medulla.
• Numerous collecting ducts converge toward the tip of the medullary pyramid.

Papillary duct

formed by merger of several collecting ducts.
• 30 papillary ducts end in the tip of each papilla.
• Collecting and papillary ducts lined with simple cuboidal epithelium

Flow of fluid from 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

Juxtamedullary nephrons

• 15% of all nephrons.
• Very long nephron loops, maintain salinity gradient in the medulla and help conserve water.
• Efferent arterioles branch into vasa recta around long nephron loop.

Cortical nephrons

• 85% of all nephrons.
• Short nephron loops.
• Efferent arterioles branch into peritubular capillaries around PCT and DCT

Renal plexus

nerves and ganglia wrapped around each renal artery.
• Follows branches of renal artery into the parenchyma of the kidney; issues nerve fibers to blood vessels and convoluted tubules of the nephron.
• Carries sympathetic innervation.
• Stimulation reduces glomerular blood flow and rate of urine production.
• Respond to falling blood pressure by stimulating the kidneys to secrete renin, an enzyme that activates hormonal mechanisms to restore blood pressure.
• Kidneys also receive parasympathetic innervation of unknown function

Kidneys convert blood plasma to urine in four stages

• Glomerular filtration.
• Tubular reabsorption.
• Tubular secretion.
• Water conservation

Glomerular filtrate

the fluid in the capsular space; similar to blood plasma except that it has almost no protein

Tubular fluid

fluid from the proximal convoluted tubule through the distal convoluted tubule; substances have been removed or added by tubular cells

Urine

fluid that enters the collecting duct; undergoes little alteration beyond this point except for changes in water content

Glomerular filtration

a special case of capillary fluid exchange in which water and some solutes in the blood plasma pass from the capillaries of the glomerulus into the capsular space of the nephron

Filtration membrane

three barriers through which fluid passes.
• Fenestrated endothelium of glomerular capillaries; 70 to 90nm filtration pores—small enough to exclude blood cells; highly permeable

Basement membrane

• Proteoglycan gel, negative charge, excludes molecules greater than 8 nm; albumin repelled by negative charge.
• Blood plasma is 7% protein, the filtrate is only 0.03% protein

Filtration slits

• Podocyte cell extensions (pedicels) wrap around the capillaries to form a barrier layer with 30 nm filtration slits.
• Negatively charged which is an additional obstacle for large anions.
Almost any molecule smaller than 3 nm can pass freely through the filtration membrane.
• Water, electrolytes, glucose, fatty acids, amino acids, nitrogenous wastes, and vitamins. Some substances of low molecular weight are bound to the plasma proteins and cannot get through the membrane.
• Most calcium, iron, and thyroid hormone.
• Unbound fraction passes freely into the filtrate

Filtration Pressure

Filtration pressure depends on hydrostatic and osmotic pressures on each side of the filtration membrane

Blood hydrostatic pressure (BHP)

• High in glomerular capillaries (60 mm Hg compared to 10to 15 in most other capillaries).
• Because afferent arteriole is larger than efferent arteriole: a large inlet and small outlet.

Hydrostatic pressure in capsular space

18 mm Hg due to high filtration rate and continual accumulation of fluid in the capsule

Colloid osmotic pressure (COP) of blood

• About the same here as elsewhere: 32 mm Hg. Glomerular filtrate is almost protein-free and has no significant COP. Higher outward pressure of 60 mm Hg, opposed by two inward pressures of 18 mm Hg and 32 mm Hg. Net filtration pressure: 60out − 18in − 32in \= 10 mm Hg out.
• High BP in glomerulus makes kidneys vulnerable to hypertension.
• It can lead to rupture of glomerular capillaries, produce scarring of the kidneys (nephrosclerosis), and atherosclerosis of renal blood vessels, ultimately leading to renal failure.

Glomerular filtration rate (GFR)

amount of filtrate formed per minute by the two kidneys combined.
• GFR \= NFP × Kf ≈ 125 mL/min or 180 L/day (male).
• GFR \= NFP × Kf ≈ 105 mL/min or 150 L/day (female).
• Net filtration pressure (NFP)
.• Filtration coefficient (Kf) depends on permeability and surface area of filtration barrier. Total amount of filtrate produced per day equals 50 to 60 times the amount of blood in the body.
• 99% of filtrate is reabsorbed since only 1 to 2 L urine excreted per day.

If GFR too high

• Fluid flows through renal tubules too rapidly for them to reabsorb the usual amount of water and solutes.
• Urine output rises.
• Chance of dehydration and electrolyte depletion.

If GFR too low

• Wastes are reabsorbed.
• Azotemia may occur.

GFR control is achieved by three homeostatic mechanisms

• Renal autoregulation.
• Sympathetic control.
• Hormonal control.
GFR controlled by adjusting glomerular blood pressure from moment to moment.

Renal autoregulation

the ability of the nephrons to adjust their own blood flow and GFR without external (nervous or hormonal) control.
Enables kidney to maintain a relatively stable GFR in spite of changes in systemic blood pressure.
Two methods of autoregulation: myogenic mechanism and tubuloglomerular feedback.

Myogenic mechanism

based on the tendency of smooth muscle to contract when stretched.

If arterial blood pressure increases

• Afferent arteriole is stretched.
• Afferent arteriole constricts and prevents blood flow into the glomerulus from changing.

If arterial blood pressure falls

• Afferent arteriole relaxes.
• Afferent arteriole dilates and allows blood to flow more easily into glomerulus, so that flow rate remains similar and filtration remains stable

Tubuloglomerular feedback

glomerulus receives feed back on the status of downstream tubular fluid and adjusts filtration rate accordingly.
• Regulates filtrate composition, stabilizes kidney performance, and compensates for fluctuations in blood pressure.

Juxtaglomerular apparatus

complex structure found at the end of the nephron loop where it has just reentered the renal cortex.
• Loop comes into contact with the afferent and efferent arterioles at the vascular pole of the renal corpuscle.

Macula densa

patch of slender, closely spaced sensory cells in nephron loop.
• When GFR is high, filtrate contains more NaCl.
• When macula densa absorbs more NaCl, it secretes ATP.
• ATP is metabolized by nearby mesangial cells into adenosine.
• Adenosine stimulates nearby granular cells

Granular (juxtaglomerular) cells

modified smooth muscle cells wrapping around arterioles (close to macula densa).
• Granular cells respond to adenosine by constricting afferent arterioles; constriction reduces blood flow which corrects GFR
• Mesangial cells might also contract, constricting capillaries and further limiting GFR
Granular cells also contain granules of renin, which they secrete in response to drop in blood pressure.
• Participate in the renin-angiotensin-aldosterone system that works to control blood volume and pressure.
Renal autoregulation regulates GFR but cannot keep it entirely constant.
• Rises in blood pressure will cause a rise in GFR.
• If mean arterial pressure drops below 70 mm Hg, filtration and urine output cease.

If GFR rises

• More NaCl is reabsorbed, and more adenosine is produced locally.
• Adenosine stimulates JG cells to contract which constricts afferent arteriole, reducing GFR to normal.

If GFR falls

• Macula relaxes afferent arterioles and mesangial cells.
• Blood flow increases and GFR rises back to normal.

Sympathetic Control

Sympathetic nerve fibers richly innervate the renal blood vessels.
Sympathetic nervous system and adrenal epinephrine constrict the afferent arterioles in strenuous exercise or acute conditions like circulatory shock.
• Reduces GFR and urine output.
• Redirects blood from the kidneys to the heart, brain, and skeletal muscles.
• GFR may be as low as a few milliliters per minute.

Renin-Angiotensin-Aldosterone Mechanism

The renin-angiotensin-aldosterone mechanism is a system of hormones that helps control blood pressure and GFR.
In response to a drop in blood pressure, baroreceptors in carotid and aorta stimulate the sympathetic nervous system.
Sympathetic fibers trigger release of renin by kidneys' granular cells.
Renin converts angiotensinogen, a blood protein, into angiotensin I.
In lungs and kidneys, angiotensin-converting enzyme (ACE) converts angiotensin I to angiotensin II

Angiotensin II

active hormone that increases BP.
• Potent vasoconstrictor raising BP throughout body.
• Constricts efferent arteriole raising GFR despite low BP.
• Lowers BP in peritubular capillaries enhancing reabsorption of NaCl and H2O.
• Stimulates adrenal cortex to secrete aldosterone, which promotes Na+ and H2O reabsorption in DCT and collecting duct.
• Stimulates Na+ and H2O reabsorption in PCT.
• Stimulates posterior pituitary to secrete ADH which promotes water reabsorption by collecting duct.
• Stimulates thirst

The Proximal Convoluted Tubule

PCT reabsorbs about 65% of glomerular filtrate, removes some substances from blood, and secretes them into tubular fluid for disposal in urine.
• Prominent microvilli and great length.
• Abundant mitochondria provide ATP for active transport.
• PCTs alone account for about 6% of one's resting ATP and calorie consumption.

Tubular reabsorption

process of reclaiming water and solutes from tubular fluid and returning them to blood.
Two routes of reabsorption
Reabsorbed fluid is ultimately taken up by peritubular capillaries.
Potassium, magnesium, and phosphate ions diffuse through the paracellular route with water. Phosphate is also cotransported into the epithelial cells with Na+. Some calcium is reabsorbed through the paracellular route in the PCT, but most Ca2+ reabsorption occurs later in the nephron. Glucose is cotransported with Na+ by sodium-glucose transport (SGLT) proteins—normally all glucose is reabsorbed.

Transcellular route

• Substances pass through cytoplasm of PCT epithelial cells and out their base.

Paracellular route

• Substances pass between PCT cells.
• Junctions between epithelial cells are leaky and allow significant amounts of water to pass through.
• Solvent drag—water carries a variety of dissolved solutes with it.

Sodium reabsorption is key

• Creates an osmotic and electrical gradient that drives there absorption of water and other solutes.
• Na+ is most abundant cation in filtrate.
• Creates steep concentration gradient that favors its diffusion into epithelial cells.
• Two types of transport proteins in the apical cell surface are responsible for sodium uptake.
• Symports that simultaneously bind Na+ and another solute such as glucose, amino acids, or lactate.
• Na+-H+ antiport that pulls Na+ into the cell while pumping out H+ into tubular fluid.
• Sodium is prevented from accumulating in epithelial cells by Na+-K+ pumps in the basal surface of the epithelium.
• Pumps Na+ out to extracellular fluid.
• Na+ is picked up by peritubular capillaries and returned to blood.
• The Na+-K+ pumps (at the base) are examples of primary active transport—they use ATP.
• The symports on the apical surface are examples of secondary active transport—they do not directly consume ATP, but are dependent on the primary transport Na+-K+ pumps at the base of the cell to establish the sodium concentration gradient.
Negative chloride ions follow the positive sodium ions by electrical attraction.
• Various antiports in the apical cell membrane that absorb Cl− in exchange for other anions they eject into the tubular fluid: K+-Cl− symport.

Nitrogenous wastes

• Nephron reabsorbs about half of urea in tubular fluid.
• Concentration remaining in blood is safe.
• PCT reabsorbs uric acid, but later portions of the nephron secrete it.
• Creatinine is not reabsorbed—it is passed in urine.
Each day, kidneys reduce 180 L of glomerular filtrate to 1 or2 L of urine. Two-thirds of water in filtrate is reabsorbed in PCT. Reabsorption of solutes makes the tubule cells and tissue fluid hypertonic to tubular fluid.
• Water follows solutes by osmosis through both paracellular and transcellular routes.
• Transcellularly, water uses channels called aquaporins.
• In PCT, water is reabsorbed at constant rate called obligatory water reabsorption.

Uptake by the Peritubular Capillaries

Peritubular capillaries reabsorb water and solutes that leave the basal surface of the tubular epithelium.
• Reabsorption occurs by osmosis and solvent drag. Three factors promote osmosis into the capillaries.
• High interstitial fluid pressure due to accumulation of reabsorbed fluid in extracellular space.
• Low blood hydrostatic pressure in peritubular capillaries due to narrowness of efferent arterioles.
• High colloid osmotic pressure in blood due to presence of proteins that were not filtered.

The Transport Maximum

The amount of solute that renal tubules can reabsorb is limited by the number of transport proteins in tubule cells' membranes. If all transporters are occupied, any excess solute passes by and appears in urine. Transport maximum is reached when transporters are saturated. Each solute has its own transport maximum.
• Any blood glucose level above 220 mg/dL results in glycosuria.

Tubular secretion

renal tubule extracts chemicals from capillary blood and secretes them into tubular fluid

Purposes of secretion in PCT and nephron loop include

• Acid-base balance:
• Secretion of varying proportions of hydrogen and bicarbonate ions helps regulate pH of body fluids.
• Waste removal:
• Urea, uric acid, bile acids, ammonia, and a little creatinine are secreted into the tubule.
• Clearance of drugs and contaminants:
• Examples include morphine, penicillin, and aspirin.
• Some drugs must be taken multiple times per day to keep up with renal clearance

The Nephron Loop

Primary function of nephron loop is to generate salinity gradient that enables collecting duct to concentrate the urine and conserve water.
Electrolyte reabsorption from filtrate.
• Thick segment reabsorbs 25% of Na+, K+, and Cl− in filtrate.
• Ions leave cells by active transport and diffusion.
• NaCl remains in the tissue fluid of renal medulla.
• Water cannot follow since thick segment is impermeable.
• Tubular fluid very dilute as it enters distal convoluted tubule.

The Distal Convoluted Tubule and Collecting Duct

Fluid arriving in the DCT still contains about 20% of the water and 7% of the salts from glomerular filtrate.
• If this were all passed as urine, it would amount to 36 L/day. DCT and collecting duct reabsorb variable amounts of water and salt and are regulated by several hormones.
• Aldosterone, atrial natriuretic peptide, ADH, and parathyroid hormone.
Summary:
• PCT reabsorbs 65% of glomerular filtrate and returns it to peritubular capillaries.
• Much reabsorption by osmosis and cotransport mechanisms linked to active transport of sodium.
• Nephron loop reabsorbs another 25% of filtrate.
• DCT reabsorbs Na+, Cl−, and water under hormonal control, especially aldosterone and ANP.
• The tubules also extract drugs, wastes, and some solutes from the blood and secrete them into the tubular fluid.
• DCT completes the process of making urine.
• Collecting duct conserves water.

Urine Formation III: Water Conservation

The kidney eliminates metabolic wastes from the body but prevents excessive water loss. As the kidney returns water to the tissue fluid and bloodstream, the fluid remaining in the renal tubules passes as urine and becomes more concentrated.

Collecting Duct

Collecting duct (CD) begins in the cortex where it receives tubular fluid from several nephrons. CD runs through medulla, and reabsorbs water, making urine up to four times more concentrated. Medullary portion of CD is more permeable to water than to NaCl. As urine passes through the increasingly salty medulla, water leaves by osmosis, concentrating urine.

The Countercurrent Multiplier

The ability of kidney to concentrate urine depends on salinity gradient in renal medulla.
• Four times more salty in the renal medulla than the cortex.
Nephron loop acts as countercurrent multiplier.
• Multiplier: continually recaptures salt and returns it to extracellular fluid of medulla which multiplies the osmolarity of adrenal medulla.
• Countercurrent : because of fluid flowing in opposite directions in adjacent tubules of nephron loop.

Fluid flowing downward in descending limb

• Passes through environment of increasing osmolarity.
• Most of descending limb very permeable to water but not to NaCl.
• Water passes from tubule into the ECF leaving salt behind.
• Concentrates tubular fluid to 1,200 mOsm/L at lower end of loop.

Fluid flowing upward in ascending limb

• Impermeable to water.
• Reabsorbs Na+, K+, and Cl− by active transport pumps into ECF.
• Maintains high osmolarity of renal medulla.
• Tubular fluid becomes dilute: 100 mOsm/L at top of loop.

Recycling of urea adds to high osmolarity of deep medulla

• Lower end of collecting duct is permeable to urea but neither thick segment of loop nor DCT is permeable to urea.
• Urea is continually cycled from collecting duct to the nephron loop and back.
• Urea remains concentrated in the collecting duct and some of it always diffuses out into the medulla adding to osmolarity.

Urinalysis

examination of physical and chemical properties of urine

Appearance

varies from clear to deep amber depending on state of hydration.
• Yellow color due to urochrome pigment from breakdown of hemoglobin (RBCs).
• Cloudiness or blood could suggest urinary tract infection, trauma, or stones; or might just be contamination with other fluids.

Pyuria

pus in the urine

Hematuria

blood in urine due to urinary tract infection, trauma, or kidney stones

Odor

bacteria degrade urea to ammonia, some foods and diseases impart particular aromas

Specific gravity

compares urine sample's density to that of distilled water.
• Density of urine ranges from 1.001 to 1.028 g/mL

Osmolarity (blood \= 300 mOsm/L)

• Ranges from 50 mOsm/L to 1,200 mOsm/L in dehydrated person

pH

range: 4.5 to 8.2, usually 6.0 (mildly acidic)

Chemical composition

95% water, 5% solutes
•Normal: urea, NaCl, KCl, creatinine, uric acid, phosphates, sulfates, traces of calcium, magnesium, and sometimes bicarbonate, urochrome, and a trace of bilirubin
•Abnormal: glucose, free hemoglobin, albumin, ketones, bile pigments.

Urine Volume

Normal volume for average adult—1 to 2 L/day
• Low output from kidney disease, dehydration, circulatory shock, prostate enlargement.
• Low urine output of less than 400 mL/day, the body cannot maintain a safe, low concentration of waste in the plasma(leads to azotemia)

Polyuria

output in excess of 2 L/day

Oliguria

output of less than 500 mL/day

Anuria

0 to 100 mL/day

Glycosuria

glucose in the urine

Diabetes

any metabolic disorder resulting in chronic polyuria

Diabetes mellitus type 1, type 2, and gestational diabetes

• High concentration of glucose in renal tubule.
• Glucose opposes the osmotic reabsorption of water.
• More water passes in urine (osmotic diuresis).
• Glycosuria

Diabetes insipidus

• ADH hyposecretion causes not enough water to be reabsorbed in the collecting duct.
• More water passes in urine

Diuretics

any chemical that increases urine volume
• Some increase GFR—e.g., caffeine dilates the afferent arteriole.
• Some reduce tubular reabsorption of water—e.g., alcohol inhibits ADH secretion.
• Some act on nephron loop (loop diuretic): inhibit Na+-K+-Cl−symport.
• Impairs countercurrent multiplier reducing the osmotic gradient in the renal medulla.
• Collecting duct unable to reabsorb as much water as usual.
• Diuretics are commonly used to treat hypertension and congestive heart failure by reducing the body's fluid volume and blood pressure.

Urine Storage and Elimination

Urine is produced continually.
Does not drain continually from the body.
Urination is episodic—occurring when we allow it.
Made possible by storage apparatus and neural controls for timely release.

Ureters

retroperitoneal, muscular tubes that extend from each kidney to the urinary bladder.
• About 25 cm long.
• Pass posterior to bladder and enter it from below.
• Flap of mucosa at entrance of each ureter acts as a valve into bladder.
• Keeps urine from backing up into ureter when bladder contracts.
Three layers of ureter- adventitia, muscularis, mucosa
• Lumen very narrow, easily obstructed by kidney stones