Urinary System, Fluids, Electrolytes and Acid-Base Balance

Components of Urinary System

• two kidneys

• two ureters

• urinary bladder

• urethra

Functions of the Kidneys

1. excrete wastes

2. regulation of blood ionic composition

3. regulate blood pH

4. regulate blood volume

5. regulate blood pressure

6. maintenance of blood osmolarity

7. production of hormones

8. regulation of blood glucose levels

Position of Kidneys in the Body

• located just above the waist between the peritoneum and the posterior wall of the abdomen

• between the levels of the last thoracic and third lumbar vertebrae

External Anatomy of Kidneys

• renal hilus: the ureter emerges from the kidney along with blood vessels, lymphatic vessels and nerves

• three layers of tissue surrounding each kidney - fibrous capsule, perineal fat capsule, renal fascia

Fibrous Capsule

• deep layer

• sheet of collagen-rich connective tissue that is continuous with the outer coat of the ureter

• serves as a barrier against trauma and helps maintain the shape of the kidney

Perineal Fat Capsule

• middle layer

• mass of fatty tissue surrounding the fibrous capsule

• protects the kidney from trauma and holds it firmly in place

Renal Fascia

• superficial layer

• a collagenous and elastic dense irregular connective tissue that anchors the kidney to the surrounding structures and abdominal wall

Internal Kidney Anatomy

• renal cortex

• renal medulla

• parenchyma

Renal Cortex

• superficial region

• extends from the fibrous capsule to the bases of the renal pyramids and into the spaces between them

• divided into an outer cortical zone and inner junxtamedullary zone

• renal columns: portions of the renal cortex that extend between renal pyraminds

Renal Medulla

• deep region

• consists of several renal pyramids

• the base of each pyramid face the renal cortex and its apex points toward the renal hilum

Parenchyma

• within are nephrons

• filtrate formed by neprhons drains into large papillary ducts which extend through the renal papillae of the pyramids

• papillary ducts drain into minor and major calyx

Path of Blood Flow through Kidneys

renal artery —> segmental arteries —> interlobar arteries —> arcuate arteries —> cortical radiate arteries —> afferent arterioles —> glomerular capillaries —> efferent arterioles —> peritubular capillaries or vasa recta —> peritubular venules —> cortical radiate veins —> arcurate veins —> interlobar veins —> renal vein

Renal Blood Flow

the blood flow through both kidneys

Segmental Arteries

supply different segments of the kidneys

Interlobar Arteries

branches from segmental arteries

enter the parenchyma and pass through the renal lobes

Kidney Lobe

consists of a renal pyramid, some of the renal column on either side of the renal pyramid and the renal cortex at the base of the renal pyramid

Arcuate Arteries

at the bases of renal pyramids

the interlobar arteries between the renal medulla and cortex

Cortical Radiate Arteries

produced by divisions of the arcuate arteries

they radiate outward and enter the renal cortex where they give off branches called afferent glomerular artierioles

Glomerulus

a round mass of nerves or blood vessels, especially the microscopic tuft of capillaries that is surrounded by the glomerular capsule of each kidney tubule

Efferent Glomerular Arteriole

carries blood out of the glomerulus

Glomerular Capillaries

positioned between two arterioles

important for urine function

Peritubular Capillaries

surround tubular parts of nephron

Vasa Recta

extending from some efferent glomerular arterioles

supply tubular portions of nephron in the renal medulla

Cortical Radiate Veins

• receive blood from the vasa recta

• blood drains through the arcuate veins to the interlobar veins

• blood leaves kidney through a single renal vein that exits at the renal hilum and carries venous blood to the inferior vena cava

Nerve Supply of the Kidneys

• many renal nerves originate in the renal ganglion and pass through the renal plexus into the kidneys

• renal nerves apart of the sympathetic part of the autonomic nervous system

• vasomotor nerves: regulate the flow of blood through the kidney by causing vasodilation or vasocontrastriction of renal arterioles

Major Parts of Nephron

1. renal corpuscle: site where blood plasma is filtered

2. renal tubule: receives the glomerular filtrate from the renal corpuscle; the filtrate further regulated as it passes through the tubule

Cortical Nephrons

• 80-85% of nephrons

• renal corpuscles are in outer renal cortex

• have short nephron loops and extend only into the outer medulla

• blood supply comes from peritubular capillaries

Juxtamedullary Nephrons

• 15.20% of nephrons

• have long nephron loops that extend into the deepest region of renal medulla

• blood supply from peritubular capillaries and vasa recta

• produce very dilute or very concentrated urine

Glomerular Capsule Components

• double walled epithelia’s cup that surrounds the glomerular capillaries

• blood plasma filtered and then filtered fluid passes into the renal tubule

Renal Tubule Parts

1. proximal convoluted tubule (PCT)

2. nephron loop

3. distal convoluted tubule (DCT)

Proximal Convoluted Tubule (PCT)

• attached to glomerular capsule

• tightly coiled

Nephron Loop

• extends into the renal medulla

• returns to renal cortex

• includes descending and ascending limb

Distal Convoluted Tubule (DCT)

• located farther from the glomerular capsule

• empties into a collecting duct

Filtration Fraction

the fraction of blood plasma in the afferent glomerular arterioles of the kidneys that become glomerular filtrate

Three Basic Functions Performed by the Nephron

• glomerular filtration

• tubular reabsorption

• tubular secretion

Glomerular Filtration

• water and most solutes in blood plasma move across the wall of glomerular capillaries where they are filtered and move into the glomerular capsule and into the renal tube

• takes place in glomerulus

Tubular Reabsorption

• renal tube reabsorb 99% of filtered water and useful solutes

• water and solutes return to the blood as it flows through the peritubular capillaries and vasa recta

Tubular Secretion

• as filtered fluid flows through the renal tubules and collecting ducts they secrete other materials into the fluid

• removes a substance from the blood

Reabsorption

the return of substances into the bloodstream

Absorption

entry of new substances into the body and occurs in digestive tract

Filtration Membrane

• permits situation of water and small solutes but prevents filtration of most blood plasma proteins and blood cells

• consists of glomerular endothelial cells, basement membrane, and filtration slit

Glomerular Endothelial Cells

• very leaky because it permits all solutes in the blood plasma to exit glomerular capillaries but prevents filtration of blood cells

Mesangial Cells

• located among glomerular capillaries in the cleft between afferent and efferent glomerular arterioles

• help regulate glomerular filtration

Basement Membrane

• layer of acellular material between the endothelium and the podocytes

• consists of minute collagen fibers and negatively charged glycoproteins

• the pores allow water and most small solutes to pass through

• glycoproteins repel blood plasma proteins so they cannot be filtered

Filtration Slit

• formed by a podocyte

• pedicels extend from each podocyte and wrap around glomerular capillaries

• filtration slit: spaces between pedicels

• slit membrane: extends across each filtration slit, permits passage of molecules including water, glucose, vitamins, amino acids, and very small blood plasma protiens

Net Filtration Pressure

• the pressure that determines the direction and rate of filtration in the glomerulus, calculated by the difference between the hydrostatic pressure and the osmotic pressure in the glomerular capillaries and Bowman's capsule.

• NFP = GBHP - CHP - BCOP

Glomerular Blood Hydrostatic Pressure (GBHP)

• the blood pressure in glomerular capillaries

• 55mmHg

• promotes filtration by forcing water and solutes in blood plasma through filtration membrane

Capsular Hydrostatic Pressure (CHP)

• hydrostatic pressure exerted against the filtration membrane by fluid already in the capsular space and renal tubule

• opposes filtration and represents a back pressure of 15mmHg

Blood Colloid Osmotic Pressure (BCOP)

• due to presence of proteins in blood plasma also opposes filtration

• 30mmHg

Loss of Blood Plasma Proteins

• can cause edema - an abnormally high volume of interstitial fluid

• glomerular capillaries are damaged and become so permeable that blood plasma proteins enter glomerular filtrate

• as a result the filtrate exerts a colloid osmotic pressure that draws water out of blood

• NFP increase and blood colloid osmotic pressure decreases

• blood volume decreases and interstitial fluid increases

Glomerular Filtration Rate (GFR)

amount of filtrate formed in all renal corpuscles of both kidneys each minute

Mechanisms that Regulate GFR Functions

1. adjust blood flow into and out of glomerulus

2. alter the glomerular capillary surface area available for filtration

Regulate GFR

• renal autoregulation

• neural regulation

• hormonal regulation

Renal Autoregulation

• maintains a nearly consistent renal blood flow and GFR despite normal changes in blood pressure

• works through myogenic mechanism and tubuloglomerular feedback

Myogenic Mechanism - When BP Increases

• stretches the walls of the afferent glomerular arteriole

• stretch triggers contraction of smooth muscle

• afferent arteriole constricts

• renal blood flow decreases

• GFR returns to normal

Myogenic Mechanism - When BP Decreases

• less stretching of smooth muscle

• afferent arterial relaxes and dilates

• renal blood flow increases

• GFR increases towards normal

Tubuloglomerular Feedback - when GFR high

• filtrate flows more rapidly through renal tubules

• less time to absorb Na, Cl, and water

• macula densa defects increased delivery of these substances

• inhibits release of nitric oxide (NO)

• less NO causes afferent arterioles to constrict

• less blood enters the glomerulus

• GFR decreases back towards normal

Role of ANS Overview

• kidney blood vessels receive sympathetic ANS fibres

• sympathetic nerves release noreponephrine

• causes vasoconstriction

Role of ANS - At Rest

• sympathetic stimulation is low

• afferent and efferent arterioles remain dilated

Role of ANS - Moderate Sympathetic Stimulation

• both arterioles constrict equally

• blood flow into and out of glomerulus decreases

• GFR decreases slightly

Role of ANS - Strong Sympathetic Stimulation

• afferent arteriole constriction predominates

• blood flow to glomerulus decreases greatly

• GFR falls significantly

Role of Angiotensin II in Regulating GFR

• reduces GFR

• powerful vasoconstrictor

• decreases renal blood flow

Role of Atrial Natriuretic Peptide (ANP)

• increases GFR

• secreted by atria of the heart

• released when atria are stretched

• relaxes glomerular mesangial cells

• increases the capillary surface area available for filtration

Tubular Reabsorption

• the return of most of the filtered water and many filtered solutes from the nephron back into the bloodstream

• reabsorption occurs along the renal tubule with the PCT making the largest contribution

Tubular Secretion

• the transfer of materials from the blood and tubule cells into the glomerular filtrate

• helps remove substances from the body through urine

Substances Secreted

• hydrogen ions

• potassium

• ammonium ions

• creatine

Tubular Secretion Functions

• helps regulate blood pH by secreting H+

• eliminates unwanted substances through urine

Paracellular Reabsorption

• substance moves between adjacent tubule cells through leaky tight junctions

• passive process

• water and some ions move

Transcellular Reabsorption - Substances Move

• through the apical membrane of a tubule cell

• across the cytosol

• through the basolateral membrane

• into the interstitial fluid

Why Reabsorption of Na+ is Important

• a large number of sodium ions pass through the glomerular filters

• one of the major solutes filtered through kidneys

• reabsorption of Na drives the reabsorption of water through osmosis

Role of Sodium Pump in Reabsorption of Na+

• renal tubule cells contain sodium-potassium ATPase pumps in the basolateral membrane

• use ATP to pump Na out of the tubule cells into the interstitial fluid

• keep concentration of Na+ low inside the cells

Primary Active Transport

• uses energy directly from ATP hydrolysis

• pumps substances across membrane

Secondary Active Transport

• uses the electrochemical gradient of an ion rather than ATP directly

• couples movement of one ion down its gradient to move another substance against its gradient

Symporters

move two or more substances in the same direction

Antiporters

move two or more substances in opposite directions

Transport Maximum

• the max rate at which transport proteins can move a substance

• measured in mg/min

• every transporter has an upper limit to how quickly it can work

Renal Threshold

• when blood glucose rises above 200mg/mL the renal symporters cannot reabsorb all of the filtered glucose

• glucose begins apprearing in the urine because the transport max has been exceeded

Obligatory Water Reabsorption

• water follows reabsorbed solutes via osmosis

• occurs in proximal tubule depending on the limb of the nephron loop

• nephron segments are always permeable to water

Facultative Water Reabsorption

• 20% of water reabsorption

• regulated by antidiuretic hormone (ADH)

• occurs in the late distal tubule, collecting duct

Glucosuria

the presence of glucose in the urine

Na+ Symporters

• located in the apical membrane of PCT cells

• transport Na+ and another substance together in the tubule cell

• reabsorb glucose, amino acids, lactic acids, water-soluble vitamins, phosphate, sulfate

in Na—Glucose Symporter

• two Na+ ions and one glucose molecule enter the cell together

• then glucose leaves the cell through the basolateral membrane by facilitated diffusion and enters the peritubular capillaries

Na+/H+ Antiporters

• located in the apical membrane

• move Na+ into the PCT cell while moving H+ out of the tubular lumen

• a form of secondary active transport

• results: Na+ reabsorption and H+ secretion

Role of Na+ Symporters in Reabsorptions

• are responsible for reclaiming important filtered nutrients that would otherwise be lost in urine

• after entering PCT cell, substances move across the basolateral membrane into the interstitial fluid and then into the peritubular capillaries

Role of Na+ Symporters in Reabsorptions Functions

• reabsorbing 100% of filtered glucose and amino acids under normal conditions

• transporting Na+ together with glucose, amino acids, lactic acid, water-soluble vitamins, phosphate, sulfate

• ensure soluble nutrients are returned to the bloodstream

Na+ Reabsorption

• Na+ enters the PCT through na/h antiporter

• H+ is simultaneously secreted into the tubular fluid

• Na+ then pumped out of the cell into the interstitial fluid and enters the peritubular capillaries

H+ Secretion

• inside PCT cell

• CO2 combines with water

• the enzyme carbonic anhydrase forms carbonic acid

• H2CO3 dissociates into H+ and HCO3-

HCO3- Reabsorption

• secreted H+ combines with filtered HCO3- in the tubular fluid to form carbonic acid

• carbonic acid breaks down into CO2 and H2O

• CO2 diffuses back into PCT cell

• inside the cell: CO2 combines with H2O again which dissociates into H+ and HCO3-, then HCO3- leaves the cell through facilitated diffusion into the bloodstream

• result: for every H+ secreted, one Na+ and one HCO3- are reabsorbed

Water Reabsorption

• reabsorption of Na+ and other solutes increases osmolarity

• osmotic gradient

• water is reabsorbed by transcellular route and paracellular route

• PCT cells are permeable to water because they contain many aquaporin-1 water channels, which greatly increase water movement across the apical and basolateral membrane

Osmotic Gradient

• water moves from the tubular fluid into the peritubular capillaries by osmosis to restore osmotic balance

How Production of Ammonia (NH3) in PCT cells can increase the Level of Bicarbonate ions in the blood

• PCT cells can produce ammonia by demoninating the amino acid glutamine

• this reaction also produces bicarbonate ions

• NH3 quickly binds with H+ to form ammonium ions (NH4)

• NH4 can substitute for H+ on the na/h antiporters and is secreted into the tubular fluid

• newly formed HCO3- moves through the basolateral membrane and enters bloodstrem

• this increases the amounf of bicarbonate in the blood providing additional buffering capacity in blood plasma

Reabsorption of the Loop of Henle

• allows the kidneys to regulate the volume and osmolarity of blood fluids independently because water reabsorption is not always coupled with solute reabsorption

• descdening limb

• ascending limb

• Na+—K+—2Cl- Symporter

Descending Limb

• reabsorbs 15% of filtered water

• water reabsorbed by osmosis

• as water leaves tubular fluid its osmolarity remains balanced with the surrounding environment

Ascending Limb

• reabsorbs 25% of filtered Na, K, and Ca, 35% of filtered Cl, 10% of filtered HCO3- and variable amounts of Mg2

• the apical membrane is virtually impermeable to water

• because ions are reabsorbed but water is not the tubular fluid becomes progressively less concentrated as it moves up the ascending limb

Role of Na+—K+—Cl- Symporter

• located in thick ascending limb

• reabsorbs 1 Na, 1 K, and 2 Cl

• main effect is reabsorption of Na and Cl

• K largely leaks back into the lumen creates a relative negative change in the interstitial fluid promoting paracellular reabsorption of Na and K

How Loop of Henle Regulates Volume and Osmolarity

• in descending limb: water is reabsorbed reducing the volume of tubular fluid

• in ascending limb: solutes are reabsorbed without water decreasing the osmolarity of the tubular fluid

Role of Na+—Cl- Symporters

• by the time fluid reaches the early distal convoluted tubule (DCT), 80% of filtered water has been reabsorbed

• early DCT reabsorbs: 5% of filtered Na and 5% of filtered Cl

• sodium-potassium pumps and Cl leakage channels in the basolateral membrane then move Na and Cl into the peritubular capillaries, completing their reabsorption

Role of Parathyroid Hormone (PTH) in Ca2+ Reabsorption

• early DCT is a major site where PTH stimulates the reabsorption of Ca2+

• the amount of Ca2+ reabsorption in the early DCT varies according to the body’s needs

• PTH increasing calcium reabsorption when needed

Principal Cells

• located in the late distal convoluted tubule and throughout the collecting duct

• contain receptors for aldosterone and ADH

• reabsorb Na

• secrete K

• intercalated cells

Hormones that Regulate Tubular Reabsorption and Secretion

• angiotensin II

• aldosterone

• ADH

• ANP

• PTH