Filter blood, producing about 200 L of filtrate, allowing toxins, metabolic wastes, and excess ions to leave the body in urine

Regulate volume and chemical makeup of the blood

Maintain the proper balance between water and salts, and acids and bases

Production of renin to help regulate blood pressure and erythropoietin to stimulate RBC production

Activation of vitamin D

Assist the liver in detoxifying

The kidneys lie in a retroperitoneal position in the superior lumbar region

The right kidney is lower than the left………

The lateral surface is convex; the medial surface is concave

Ureters, renal blood vessels, lymphatics, and nerves enter and exit at the hilus

fibrous capsule-tight to kidney

adipose tissue cushions outside of that

fascia anchors the kidneys in place

three regions

cortex on the outside

medulla under the cortex

can divide the medulla into pyramids

pelvis

starts as minor calyces, then major calyces

feeds into the ureter

renal arteries

about 25% of  cardiac output goes into these

many branches feed all the kidney tissue

renal veins trace the opposite pattern

network of nerves regulates and adjusts blood flow 

Each kidney has about a million nephrons

The number of nephrons does not increase after birth

The kidney grows because the existing nephrons increase in size

When they are damaged they are not replaced

You need about 1/3 to be functional to ensure survival

About 99% of the liquid filtered out of the blood is returned to the blood

spherical structure

capsule

capillary network - glomerulus

a tubular structure that encloses a tangle of capillaries at its beginning

with a capillary bed between the two 

efferent afferent

the efferent arteriole leads into another capillary bed

the glomerulus 

the peritubular capillaries 

so…every  nephron has TWO associated capillary beds

tangle of capillaries – part of the nephron

a unique formation – fed and drained by arterioles

the afferent leads in and the efferent leads out

pressure in the glomerulus is high because the incoming arteriole diameter is larger than the efferent

arise from efferent arterioles – are nearby the nephron

these are LOW pressure

empty into nearby venules

blood pressure is high in the renal arteries and very low in the renal veins

blood pressure is high in the renal arteries and very low in the renal veins

Afferent arteriole leads in

Efferent arteriole leads out

this is two layers

epithelial tissue lines the capsule and wraps back around to cover over the glomerulus

in this case there is a definite space between the layers

that is where the filtrate will accumulate after it passes out of the pores and between the SLITS

The external parietal layer is a structural layer

The visceral layer consists of modified, branching epithelial cells

Porous endothelium of the glomerular capillaries - PORES

Visceral membrane of the glomerular capsule which has the SLITS

Basement membrane composed of fused basal laminae of the other layers

metabolic wastes (urea, uric acid, ammonia)

excess ions

lots of water

glucose

fatty acids

amino acids

vitamins

composed of cuboidal cells with numerous microvilli and mitochondria

Reabsorbs water and solutes from filtrate

a single layer of epithelial cells

most substances move into these cells from the lumen – not between

many substances are reclaimed here

routed back into the nearby blood 

           vessels

hairpin-shaped loop of the renal tubule

descending, and ascending portions

hairpin-shaped loop of the renal tubule

descending, and ascending portions

the ascending part of the loop changes to a THICK segment

no water escapes

these cells are more cuboidal again

Thick and thin refers to cells not to diameter of lumen

cuboidal cells without microvilli that function more in secretion (INTO THE URINE) than reabsorption

don’t need microvilli

ions, acids moved from blood to filtrate here

sodium and calcium are moved back to blood –so there is some reclamation here, too)

water is reabsorbed to blood-by hormonal control

the Juxtaglomerular Complex

the cells of the DCT are next to the glomerular capsule as the tubule loops nearby

some of them are taller 

called MACULA DENSA

chemoreceptors that react to changes in salt content of the filtrate

so this sensing system lies at a perfect spot to measure

BLOOD PRESSURE

SOLUTES IN THE BLOOD

able to secrete 

erythropoietin to increase RBCs

renin to raise blood pressure

these ducts receive urine from many nephrons

carry it toward the renal pelvis

this is the last chance for adjustments to be make to the urine

things may be added

things may be reclaimed

urine arrives here from the nephron

here is how it may be modified….

mostly water is taken back to the blood in these ducts

ADH acts here

is released when the brain senses changes in the osmotic pressure of your fluids

if you are dehydrated = ADH secreted = acts on the collecting ducts to save water back to blood

this keeps the blood pressure up

urine will be quite concentrated

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

are low-pressure, porous capillaries adapted for absorption that: 

Arise from efferent arterioles

Cling to adjacent renal tubules

Eventually empty into the renal venous system

FILTRATION

REABSORPTION

SECRETION

your kidneys make urine in an attempt to maintain homeostasis of the blood

proper amount and type of solutes

proper volume and pressure

done in three steps

The kidneys filter the body’s entire plasma volume 60 times each day

The filtrate:

about 180 to 200L of filtrate produced daily

Contains all plasma components except globular protein

Adjusts  water, nutrients, and essential ions to become urine

The urine contains metabolic wastes and unneeded substances

Its filtration membrane is specialized to restrict

Glomerular blood pressure is higher than other capillary beds

facilitated diffusion

across a membrane  with no need for energy

active transport

needs energy

pumps or carrier proteins

two substrate move, one down its gradient, the other gets a free ride

countertranport

two ions move in opposite directions

specific substrate will bind to carrier protein for transport

a carrier protein usually moves ions in one direction – Ex. down a gradient

cells can move a substance in by one type of carrier and out by another

one cell has various types of carriers

transport is limited by the number of carriers

Tm = transport maximum 

specific substrate will bind to carrier protein for transport

a carrier protein usually moves ions in one direction – Ex. down a gradient

cells can move a substance in by one type of carrier and out by another

one cell has various types of carriers

transport is limited by the number of carriers

Tm = transport maximum 

how much of the ion has to be in the blood to use up all the carriers – pass the transport maximum

now the compound or ion shows up in the urine

various amounts for compounds

Ex. glucose – 180 mg/dL

Osmolality

The number of solute particles dissolved in 1L of water

Reflects the solution’s ability to cause osmosis

in milliosmols (mOsm)

The kidneys keep the solute load of body fluids constant at about 300 mOsm

This is accomplished by the countercurrent mechanisms

a type of Plasma Protein produced by liver

not used as fuels

called albumin – are more than half the proteins found in blood

acts as a shuttle for certain molecules, also are a buffer system  and……

are the major molecule that contributes to the osmotic pressure of the blood

water moves toward them (down its own concentration gradient)

plasma proteins are not filtered out of the glomerulus and are used to maintain osmotic pressure of the blood

water follows these proteins, too

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

Glomerulus 

Peritubular capillaries

Every nephron is served by two capillary beds

Each glomerulus is: 

Fed by an afferent arteriole 

Drained by an efferent arteriole

have deep loop of Henle

So have long straight capillaries that extend from the efferent arteriole = VASA RECTA

make concentrated urine

done across the three layered filtration membrane

liquid is squeezed out of the blood plasma

glomerular hydrostatic pressure

but there is back pressure by liquid in the capsule

AND colloid osmotic pressure is the movement of water back into the plasma because it is ATTRACTED TO THE PLASMA PROTEINS

also called oncotic pressure

large plasma proteins draw water toward themselves

this is the pressure of water trying to move across membranes to dilute out those large proteins (water moving down its concentration gradient)

osmotic pressure is water pushing to get to another place

in this case into the plasma

equals the glomerular hydrostatic pressure minus the osmotic pressure of glomerular blood, combined with the capsular hydrostatic pressure  - NOTE; THOSE THREE FORCES

Ultimately more fluid is forced out than attracted back in

The total amount of filtrate formed per minute by your kidneys

Total surface area of your healthy nephrons

Filtration membrane permeability – how intact is your membrane

how many proteins attract water back to blood

how much pressure in your pipes

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

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

Renal autoregulation (intrinsic system)

Neural controls (autonomic system)

Hormonal mechanism (the renin-angiotensin system)

How do your kidneys keep a steady rate based on your daily activities

Three mechanisms control the GFR-maintain homeostasis  

Autoregulation includes 

Muscles– afferent and efferent arterioles have muscles that control

Renal blood vessels are maximally dilated

Autoregulation mechanisms prevail

Extrinsic Controls-The Nervous System

Under stress

Norepinephrine is released by the sympathetic nervous system

Epinephrine is released by the adrenal medulla 

Afferent arterioles constrict and filtration is inhibited  

The sympathetic nervous system also stimulates the renin-angiotensin mechanism

refer back to the JGC

this complex (or apparatus) senses and secretes

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

Macula densa

Tall, closely packed distal tubule cells 

Lie adjacent to JG cells 

Function as chemoreceptors or osmoreceptors

Reduced stretch of the granular JG cells

Stimulation of the JG cells by activated macula densa cells-tell their neighbors….

Direct stimulation of the JG cells by renal nerves

Renin release is triggered by:

Renin acts on angiotensinogen to release angiotensin I  

Angiotensin I is converted to angiotensin II 

Angiotensin II: 

Vasoconstriction

Stimulates the adrenal cortex to release aldosterone 

As a result, both systemic and glomerular hydrostatic pressure rise

BP declines in glomerulus

may be a fall in systemic pressure

may be a clot or blockage in renal artery

or nervous system stimulates (sympathetic

Renin is secreted – WHY??

BP declines in glomerulus

capillary beds = brief vasoconstriction

constriction of efferent arteriole

secretion of ALDOSTERONE-save sodium and then water

thirst

ADH secreted to save water back to blood

Angiotensin II is ultimate result --

A transepithelial process whereby most tubule contents are returned to the blood

Transported substances move through three membranes  

Tube side (luminal) (1) and basolateral membranes (2) of tubule cells

front then back doors of tubule cells

Endothelium of peritubular capillaries (3)

All organic nutrients are reabsorbed

Ex. glucose, amino acids

Water and ion reabsorption is hormonally controlled

Ex. sodium, Mg. sulfates, K

Reabsorption may be an active (requiring ATP) or passive process (as with urea)

Note: filtration is blood to filtrate

tubular reabsorption is the REVERSE

is almost always by active transport

Na+ enters the tubule cells at  the luminal membrane

Is actively transported out of the tubules by a Na+-K+ ATPase pump

From there it moves to peritubular capillaries 

Na+  moves from filtrate into tubule cells and out into tissue fluid and into capillaries

So those cuboidal cells move many substances back into the BLOOD

water, glucose, amino acids, potassium, chloride

remember they have microvilli on their surface for maximum surface area

most water is reclaimed here

slip through a carrier protein – facilitated diffusion

active transport – pump needs ATP

cotransport- two substrates move together, one down its gradient

countertransport – opposite directions

A transport maximum (Tm): 

Reflects the number of carriers in the renal tubules available 

Exists for nearly every substance that is actively reabsorbed

Lack carriers

Are not lipid soluble

Are too large to pass through membrane pores

Urea, creatinine, and uric acid are the most important nonreabsorbed or incompletely resorbed substances

Urea, creatinine, and uric acid are the most important nonreabsorbed or incompletely resorbed substances

Sodium, all nutrients, cations, anions, and water

Urea and lipid-soluble solutes

Small proteins

the limbs of the Loop of Henle are close

separated by just fluid in the area

there is an exchange of materials because they lie so close together – but their contents are moving in opposite directions

water freely moves out of the descending limb, not much solutes

opposite in ascending limb

with much sodium leaving and being in the surrounding area

this is a positive feedback loop

the sodium is close enough to the descending limb to ‘lure’ water out of that portion

the filtrate moving on to the ascending limb is higher in solutes

so there is a gradient

sodium leaves in the ascending limb

 by pumping out solutes (salt), the ascending part of the loop indirectly concentrates fluid, that is coming to it from the previous segment

this is the countercurrent multiplier system

A POSITIVE FEEDBACK LOOP 

Done in the distal convoluted tubule

Essentially reabsorption in reverse, where substances move from peritubular capillaries or tubule cells into filtrate

Tubular secretion is important for:

Disposing of substances not already in the filtrate 

Eliminating undesirable substances such as urea and uric acid that are in the filtrate

Ridding the body of excess potassium ions

Controlling blood pH **

still some reclaiming of materials 

sodium , chloride

mostly SECRETION

if levels in the passing peritubular capillaries get too high, ions will diffuse into the nearby space

the tubular cells would reabsorb these and add them to the passing filtrate

Chemicals that enhance the urinary output include:

Any substance not reabsorbed

Ex. glucose in the diabetic

Substances that exceed the ability of the renal tubules to reabsorb it

Substances that inhibit Na+ reabsorption

Ex. caffeine

Filtrate can be diluted in the ascending loop of Henle

Dilute urine is created by allowing this filtrate to continue into the renal pelvis – WITHOUT REMOVING WATER

This will happen as long as antidiuretic hormone (ADH) is not being secreted to act on the collecting ducts

Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma) – very dilute

merging DCT here – all delivering urine

aldosterone works here also

keeps sodium pumped back into system

ADH works here 

causes water pores to form and TAKE BACK water (increase BP)

UREA is also reabsorbed to an extent

with no ADH

no water pores in CT

so lots of water lost in urine

with ADH present

water pores form

water is SAVED back to blood

all those solutes in the renal medulla have to go back into the blood at some point

without disrupting the concentration gradient

this is the function of the long straight capillaries that drape over the juxtamedullary  nephrons

water and solutes are carried out of the medulla and into the cardiovascular system

so the vasa recta allows nutrients to be delivered but is constantly mopping up solutes and water

contributes to concentrated urine

as blood flows back up toward the cortex

picks up water, and loses salt

so the vasa recta keeps water from building up in the tissues of the kidneys

Interaction between the flow of filtrate through the loop of Henle (countercurrent multiplier) and the flow of blood through the vasa recta blood vessels (countercurrent exchanger)

Color and transparency

Clear, pale to deep yellow (due to urochrome)

Concentrated urine has a deeper yellow color

Drugs, vitamin supplements, and diet can change the color of urine

Cloudy urine may indicate infection of the urinary tract

Odor

Fresh urine is slightly aromatic

Standing urine develops an ammonia odor

Some drugs and vegetables (asparagus) alter the usual odor

pH 

Slightly acidic (pH 6) with a range of 4.5 to 8.0

Diet can alter pH

Specific gravity

Ranges from 1.001 to 1.035 

Is dependent on solute concentration

Urine is 95% water and 5% solutes

Nitrogenous wastes: urea, uric acid, and creatinine

Other normal solutes include:

Sodium, potassium, phosphate, and sulfate ions

Calcium, magnesium, and bicarbonate ions 

Abnormally high concentrations of any urinary constituents may indicate pathology

Urine is 95% water and 5% solutes

Nitrogenous wastes: urea, uric acid, and creatinine

Other normal solutes include:

Sodium, potassium, phosphate, and sulfate ions

Calcium, magnesium, and bicarbonate ions 

Abnormally high concentrations of any urinary constituents may indicate pathology

actively secreted throughout the tubule

most of these come from metabolic reactions

the epithelial cells of the tubules and the collecting ducts secrete these ions into the filtrate

at the same time reabsorbing bicarbonate ions

cells of tubule produce ammonia which then binds with the hydrogen ions = ammonium

which is how hydrogen is lost in filtrate

lots of active reabsorption in PCT, which causes WATER to follow

so sodium goes back into the blood via the peritubular capillaries

all along the rest of the tubule sodium is taken back into the blood (97%)

but aldosterone and ADH can affect the reabsorption of sodium and water to maintain homeostasis

potassium ions

most are actively resorbed in PCT

some are secreted in DCT and CD

many are removed from the body in a trade – saving sodium and getting rid of potassium

most is reclaimed all along the tubule

parathyroid hormone will control, especially at DCT

Slender tubes that convey urine from the kidneys to the bladder

Ureters enter the base of  the bladder through the posterior wall

This closes their distal ends as bladder pressure increases and prevents backflow of urine into the ureters 

Ureters have a trilayered wall  

Transitional epithelial mucosa

Smooth muscle muscularis

Fibrous connective tissue adventitia

Ureters actively propel urine to the bladder via response to smooth muscle stretch

Smooth, collapsible, muscular sac that stores urine

It lies retroperitoneally on the pelvic floor posterior to the pubic symphysis

Males – prostate gland surrounds the neck inferiorly

Females – anterior to the vagina and uterus

Trigone – triangular area outlined by the openings for the ureters and the urethra

Clinically important because infections tend to persist in this region

The bladder wall has three layers  

Transitional epithelial mucosa

A thick muscular layer

A fibrous adventitia

The bladder is distensible and collapses when empty 

As urine accumulates, the bladder expands without significant rise in internal pressure

Muscular tube that:

Drains urine from the bladder

Conveys it out of the body

Sphincters keep the urethra closed when urine is not being passed

Internal urethral sphincter – involuntary sphincter at the bladder-urethra junction

External urethral sphincter – voluntary sphincter surrounding the urethra as it passes through the urogenital diaphragm

The act of emptying the bladder

Distension of bladder walls initiates spinal reflexes that:

Stimulate contraction of the external urethral sphincter

Inhibit the detrusor muscle and internal sphincter (temporarily)

Voiding reflexes:

Stimulate the detrusor muscle to contract

Inhibit the internal and external sphincters

hypothalamus has receptors for water concentration

if the brain detects a need for more water in the bloodstream

hypothalamus tells the pituitary gland to secrete ADH

ADH goes to kidney

kidney tubules become more permeable to water so more of it can be TAKEN BACK from the filtrate into the blood

ANP reduces blood Na+ which:

Decreases blood volume

Lowers blood pressure

 HOW??? ANP lowers blood Na+ by:

Acting directly on medullary collecting ducts to inhibit Na+ reabsorption

Counteracting the effects of angiotensin II

large proteins cannot pass through the membrane

 RBCs, WBCs are too large

BUT damaged kidneys allow many products to pass into the urine

casts of the tubules

crystals in large quantity

glucose should be conserved into the blood

Ex. huge quantities of glucose in diabetes = spill over into urine

pH of urine goes down in diabetes as kidneys try to keep blood pH homeostatic

kidney damage =

loss of calcium out of blood into urine

GI tract tries to absorb more to compensate

Vitamin D must be present to take up calcium in gut

Vitamin D needs to be activated by the kidneys which are damaged…

so parathyroid glands release PTH to get calcium from bones

leads to osteoporosis

bones also release phosphate, so now you have to get rid of extra phosphate (which is done by the kidneys) – which aren’t working

as phosphate increases it forms insoluble units in the blood and precipitates into soft tissue = blindness, arthritis, itching skin

also precipitates out in the kidney and accelerates kidney failure

kidney damage =

loss of calcium out of blood into urine

GI tract tries to absorb more to compensate

Vitamin D must be present to take up calcium in gut

Vitamin D needs to be activated by the kidneys which are damaged…

so parathyroid glands release PTH to get calcium from bones

leads to osteoporosis

bones also release phosphate, so now you have to get rid of extra phosphate (which is done by the kidneys) – which aren’t working

as phosphate increases it forms insoluble units in the blood and precipitates into soft tissue = blindness, arthritis, itching skin

also precipitates out in the kidney and accelerates kidney failure

acute kidney failure – function rapidly lost

hypovolemia

dehydration

diuretics over used

obstruction of renal vessels

infection of the kidney or inflammation

ibuprofen, some antibiotics, radiology dyes

crushing injuries with massive muscle breakdown

kidneys  are clogged with cells

multiple myeloma

obstruction of bladder or prostatic hypertrophy

tumors

acute kidney failure – function rapidly lost

hypovolemia

dehydration

diuretics over used

obstruction of renal vessels

infection of the kidney or inflammation

ibuprofen, some antibiotics, radiology dyes

crushing injuries with massive muscle breakdown

kidneys  are clogged with cells

multiple myeloma

obstruction of bladder or prostatic hypertrophy

tumors

chronic kidney failure – develops over months or years with poor prognosis

poorly controlled diabetes

poorly controlled HTN

long-term inflammation of glomerulus

polycystic kidney disease

kidney stones

chronic kidney failure – develops over months or years with poor prognosis

poorly controlled diabetes

poorly controlled HTN

long-term inflammation of glomerulus

polycystic kidney disease

kidney stones

if there is a tumor or injury to that part of the brain that controls ADH secretion

too little ADH may be produced

causes DIABETES INSIPIDUS

person produces 25-30 liters of DILUTE urine a day

if there is a tumor or injury to that part of the brain that controls ADH secretion

too little ADH may be produced

causes DIABETES INSIPIDUS

person produces 25-30 liters of DILUTE urine a day

because the kidneys can regulate the volume and contents of the blood by doing so

excreting various solutes = water follows

get rid of both in PROPER amounts

urea is from …?

creatinine is from…?

uric acid from RNA bases

throughout your day and your week you eat, drink and move at different rates

Ex. one day you drink more water

Ex. one day you don’t exercise

the kidneys need to maintain water and solute balance in your body –AND THEY RESPOND AND ADAPT TO YOUR VARIED SCHEDULE

You urinate out more or less concentrated urine and the volume varies

throughout your day and your week you eat, drink and move at different rates

Ex. one day you drink more water

Ex. one day you don’t exercise

the kidneys need to maintain water and solute balance in your body –AND THEY RESPOND AND ADAPT TO YOUR VARIED SCHEDULE

You urinate out more or less concentrated urine and the volume varies

also considered a hormone

starting substance = a cholesterol-like substanceUV light shining on the skin converts this into another substance ( which substance you can also get in your diet)

the liver processes it further, sending it on to the kidney, which also processes it into the final product - calcitriol

Vitamin D is needed to absorb calcium