ap ch 24 urinary system

function of kidneys

major excretory organ; maintain the body’s internal environment by:

• regulating total water volume and total solute concentration in water

• regulating ion concentrations in extracellular fluid (ECF)

• ensuring long-term acid-base balance

• excreting metabolic wastes, toxins, drugs

• producing erythropoietin and renin

activates vitamin D

carries out gluconeogenisis if needed

renin

regulates blood pressure

erythropoietin

regulates RBC production

urinary system

kidneys, ureters, urinary bladder, urethra

location and external anatomy of kidneys

retroperitoneal, in superior lumbar region

located between T12 and L5

right kidney is lower because of liver

adrenal gland sits atop each kidney

convex lateral surface

concave medial surface with vertical renal hilum leads to internal space, renal sinus

ureters, renal blood vessels, lymphatics, and nerves enter and exit at hilum

renal facia

1st layer of supportive tissue around kidney

anchoring outer layer of dense fibrous connective tissue

perirenal fat capsule

2nd layer of supportive tissue around kidney

fatty cushion

fibrous capsule

3rd layer of supportive tissue around kidney

transparent capsule that prevents spread of infection to kidney

kidney trauma

upper parts of both kidneys are protected by thoracic cage

perirenal fat provides cushioning

lower parts of kidneys are susceptible to blunt trauma (especially RIGHT kidney)

• ex. falls, car accidents, or contact sports injuries

renal artery is especially vulnerable to injury from rapid deceleration during car crashes, lead to lacerations or thrombosis (blood clot)

hematuria (blood in urine) is an important sign of such trauma

surgical treatment may be required

internal gross anatomy

internal kidney has 3 distinct regions:

• renal cortex, renal medulla, renal pelvis

renal cortex

granular-appearing superficial region

renal medulla

deep to cortex, composed of cone-shaped medullary (renal) pyramids

medullary (renal) pyramids

broad base faces cortex

papilla (tip of pyramid) points internally

separated by renal columns (inward extensions of cortical tissue)

lobe

medullary pyramid and its surrounding cortical tissue

about 8 per kidney

renal pelvis

funnel-shaped tube continuous with ureter

contains minor and major calyces

minor calyces

cup-shaped areas that collect urine draining from pyramidal papillae

major calyces

areas that collect urine from minor calyces

empty urine into renal pelvis

urine flow

renal pyramid → minor calyx → major calyx → renal pelvis → ureter

pyelitis

infection of renal pelvis and calyces

pyelonephritis

infection or inflammation of entire kidney

infections in females are usually caused by fecal bacteria entering urinary tract

severe cases can cause swelling of kidney and abscess formation, and pus may fill renal pelvis

if left untreated, kidney damage may result

normally is successfully treated with antibiotics

blood supply of kidneys

kidneys cleanse blood and adjust its composition

rich in supply

renal ateries

deliver about one-fourth (1200ml) of cardiac output to kidneys each minute

arterial flow

renal → segmental → interlobar → arcuate →cortical radiate (interlobular)

venous flow

cortical radiate → arcuate → interlobar → renal

no segmental

nerve supply of kidneys

via sympathetic fibers from renal plexus

blood vessels of kidney and their flow

aorta → renal artery → segmental artery → interlobar artery → arcuate artery → cortical radiate artery → afferent arteriole → glomerulus (capillaries) → efferent arteriole → peritubular capillaries or vasa recta → cortical radiate vein → arcuate vein → interlobar vein → renal vein → inferior vena cava

nephrons

structural and functional units that form urine

greater than 1 million per kidney

two main parts: renal corpuscle and renal tubule

renal corpuscle

2 parts

glomerulus and glomerular capsule

glomerulus

ball of yarn-like tuft of capillaries composed of fenestrated endothelium

highly porous

allows for efficient filtrate formation

different from other capillary beds because they’re fed and drained by arterioles

blood pressure is high because:

• afferent arterioles are larger in diameter than efferent

• arterioles are high-resistance vessels

filtrate

plasma-derived fluid that renal tubules process to form urine

glomerular (bowman’s) capsule

cup-shaped, hollow structure surrounding glomerulus 

consists of 2 layers:

• parietal layer: simple squamous epithelium

• visceral layer: clings to glomerular capillaries; branching epithelial podocytes

  • extensions terminate in foot processes that cling to basement membrane

  • filtration slits between foot processes allow filtrate to pass into capsular space

renal tubule

about 3 cm (1.2 in) long

consists of single layer of epithelial cells, but each region has its own unique histology and function

3 major parts:

• proximal convoluted tubule (closest to renal corpuscle)

• nephron loop

• distal convoluted tubule (farthest from renal corpuscle)

  • drains into collecting duct

collecting ducts

receive filtrate from many nephrons

run through medullary pyramids and give them their striped appearance

fuse together to deliver urine through papillae into minor calyces

has two cell types:

• principal cells: sparse with short microvilli and maintain water and Na+ balance

• intercalated cells: cuboidal cells with abundant microvilli

  • two types: A and B both help maintain acid-base balance of blood

cortical nephrons

make up 85% of nephrons

almost entirely in cortex

juxtamedullary nephrons

long nephron loops deeply invade medulla

ascending limbs have thick and thin segments

important in production of concentrated urine

nephron capillary beds

renal tubules associated with glomerulus and peritubular capillaries

juxtamedullary nephrons associated with vasa recta

glomerulus

afferent arteriole of glomerulus

arises from cortical radiate arteries and enters glomerulus

efferent arteriole of glomerulus

feed into either peritubular capillaries or vasa recta and leaves glomerulus

vasa recta

long, thin-walled vessels parallel to long nephron loops of juxtamedullary nephrons

arise from efferent arterioles serving juxtamedullary nephrons

• instead of peritubular capillaries

function in formation of concentrated urine

juxtaglomerular complex (JGC)

each nephron has 1

involves modified portions of:

• distal portion of ascending limb of nephron loop

• afferent (sometimes efferent) arteriole

important in regulating rate of filtrate formation and blood pressure

3 cell populations: macula densa, granular cells, extraglomerular mesangial cells

macula densa

tall, closely packed cells of ascending limb

contain chemoreceptors that sense NaCl content of filtrate

granular cells (juxtaglomerular cells)

enlarged, smooth muscle cells of arteriole

act as mechanoreceptors to sense blood pressure in afferent arteriole

contain secretory granules that contain renin

extraglomerular mesangial cells

located between arteriole and tubule cells

interconnected with gap junctions

may pass signals between macula densa and granular cells

physiology of kidney

180 L of fluid processed daily, but only 1.5 L of urine is formed

filter body’s entire plasma volume 60 times each day

consume 20-25% of oxygen used for body at rest

filtrate (produced by glomerular filtration) is basically blood plasma minus proteins

urine is produced from filtrate

urine

less than 1% of original filtrate

contains metabolic wastes and unneeded substances

3 processes of urine formation and adjustment of blood composition

glomerular filtration: produces cell and protein free filtrate

tubular reabsorption: selectively returns 99% of substances from filtrate to blood in renal tubules and collecting ducts

tubular secretion: selectively moves substances from blood to filtrate in renal tubules and collecting ducts

glomerular filtration

step 1 of urine formation

passive process (no metabolic energy required)

hydrostatic pressure forces fluids and solutes through filtration membrane into glomerular capsule

no reabsorption into capillaries of glomerulus occurs

filtration membrane

porous membrane between blood and interior of glomerular capsule

• allows water and solutes smaller than plasma proteins to pass

  • normally no cells can pass

contains 3 layers:

• fenestrated endothelium of glomerular capillaries

• basement membrane: fused basal laminae of 2 other layers

• foot processes of podocytes with filtration slits; slit diaphragms repel macromolecules

action of filtration membrane

macromolecules “stuck” are engulfed by glomerular mesangial cells

allows molecules smaller than 3 nm to pass

• water, glucose, amino acids, nitrogenous wastes

plasma proteins remain in blood to maintain colloid osmotic pressure

• prevents loss of all water to capsular space

• proteins in filtrate indicate membrane problem

outward pressures

affect filtration

forces that promote filtrate formation

hydrostatic pressure in glomerular capillaries (HPgc) is essentially glomerular blood pressure

chief force pushing water, solutes out of blood

quite high: 55 mmHg

• compared to ~26 mmHg seen in most cap. beds

reason is that efferent arteriole is a high-resistance vessel with a diameter smaller than afferent

inward pressures

affect filtration

forces inhibiting filtrate formation

hydrostatic pressure in capsular space (HPcs): filtrate pressure in capsule; 15 mmHg

coilloid osmotic pressure in capillaries (OPgc): “pull” of proteins in blood; 30 mmHg

net filtration pressure (NFP)

sum of forces

55 mmHg forcing out - 45 mmHg opposing = net outward force of 10 mmHg

pressure responsible for filtrate formation

main controllable factor determining glomerular filtration rate (GFR)

glomerular filtration rate (GFR)

volume of filtrate formed per minute by both kidneys (normal=120 to 125 ml/min)

directly proportional to:

• net filtration pressure: primary pressure is glomerular hydrostatic pressure

• total surface area available for filtration: glomerular mesangial cells control by contracting

• filtration membrane permeability: much more permeable than other capillaries

regulation of glomerular filtration

constant GFR is important as it allows kidneys to make filtrate and maintain extracellular homeostasis

goal of local intrinsic controls (renal autoregulation): maintain GFR in kidney

goal of extrinsic controls: maintain systemic blood pressure

GFR affects on systemic blood pressure

increased rate causes increased urine output, which lowers blood pressure and vice versa

intrinsic controls (renal autoregulation)

maintains nearly constant GFR when MAP is in range of 80-180 mmHg

regulation ceases if out of that range

2 types: myogenic mechanism and tubuloglomerular feedback mechanism

myogenic mechanism

local smooth muscle contracts when stretched

increased BP causes muscle to stretch, leading to constriction of afferent arterioles

• restricts blood flow into glomerulus

• protects glomeruli from damaging high BP

decreased BP causes dilation of afferent arterioles

both help to maintain normal GFR despite normal fluctuations in blood pressure

tubuloglomerular feedback mechanism

flow-dependent mechanism directed by macula densa cells

• respond to filtrates NaCl concentration

if GFR increases, filtrate flow rate increases

• leads to decreased reabsorption time, causing high NaCl levels in filtrate

• feedback causes constriction of afferent arteriole, which lowers NFP and GFR, allowing more time for NaCl reabsorption

opposite mechanism for decreased GFR

extrinsic controls

neural and hormonal mechanisms

purpose is to regulate GFR to maintain systemic blood pressure

will override renal intrinsic controls if blood volume needs to be increased

uses sympathetic nervous system and renin-angiotensin-aldosterone mechanism

sympathetic nervous system

under normal conditions at rest

• renal blood vessels dilated

• renal autoregulation mechanisms prevail

under abnormal conditions, like extremely low ECF volume (low BP)

• norepinephrine is released by SNS and epinephrine is released by adrenal medulla, causing:

  • systemic vasoconstriction, increasing BP

  • constriction of afferent arterioles, decreasing GFR

  • blood volume and pressure increases

  • SNS

renin-angiotensin-aldosterone mechanism

main mechanism for increasing BP

3 pathways to renin release by granular cells:

• direct stimulation of granular cells by sympathetic nervous system

• stimulation by activated macula densa cells when filtrate NaCl concentration is low

• reduced stretch of granular cells

other factors affecting GFR

renal cells release a variety of chemicals

some chemicals act as paracrines that affect renal arterioles, like adenosine and prostaglandin E2

some cells make their own locally acting angiotensin II that reinforces the effects of hormonal angiotensin II

tubular reabsorption

step 2 of urine formation

quickly reclaims most of tubular contents and returns them to blood

selective transepithelial process

• almost all organic nutrients are reabsorbed

• water and ion reabsorption is hormonally regulated and adjusted

includes active and passive tubular reabsorption

substances can follow 2 routes (transcellular and paracellular)

transcellular route

solute enters apical membrane of tubule cells

travels through cytosol of tubule cells

exits basolateral membrane of tubule cells

enters blood through endothelium of peritubular capillaries

paracellular route

between tubule cells

limited by tight junctions, but leaky in proximal nephron

water, Ca2+, Mg2+, K+, and some Na+ in the PCT move via this route

tubular reabsorption of sodium

sodium transport across the basolateral membrane

Na+ is most abundant cation in filtrate

transport across apical membrane

• active pumping of Na+ at basolateral membrane results in strong electrochemical gradient within tubule cell

  • results in low intracellular Na+ levels that facilitates Na+ diffusion

  • K+ leaks out of cell into interstitial fluid, leaving a net negative charge inside cell, which also acts to pull Na+ inward

tubular reabsorption of nutrients, water, and ions

Na+ reabsorption by primary active transport provides energy and means for reabsorbing almost every other substance

uses secondary active transport and passive tubular reabsorption of water

secondary active transport

organic nutrients reabsorbed by this are cotransported with Na+

glucose, amino acids, some ions, vitamins

passive tubular reabsorption of water

movement of Na+ and other solutes creates osmotic gradient for water

water is reabsorbed by osmosis, aided by water-filled pores called aquaporins

uses obligatory water reabsorption facultative water reabsorption

obligatory water reabsorption

aquaporins are always present in PCT

in proximal convoluted tubule and gives its toys away but then it wants them all back

facultative water reabsorption

aquaporins are inserted in collecting ducts only if ADH is present

act based on concentration of water right before if becomes urine

transport maximum (Tm)

transcellular transport system are specific and limited

exists fro almost every reabsorbed substance

• reflects number of carriers in renal tubules that are available

when carriers for a solute are saturated, excess is excreted in urine

• ex. hyperglycemia leads to high blood glucose levels that exceed Tm, and glucose spills over into urine

proximal convoluted tubule reabsorptive capabilities

site of most reabsorption

all nutrients, such as glucose and amino aicds, are reabsorbed

65% of Na+ and water reabsorbed

many ions

almost all uric acid

about half of urea (later secreted back into filtrate)

nephron loop reabsorptive capabilities

descending limb: H2O can leave, solutes/ions cannot

ascending limb: H2O cannot leave, solutes/ions can 

thin segment is passive to Na+ movement 

thick segment has Na+-K+-2Cl- symporters and Na+-H+ antiporters that transport Na+ into cell

some Na+ can pass into cell by paracellular route in this area of limb

distal convoluted tubule and collecting duct reabsorptive capabilities

reabsorption is hormonally regulated in these areas

uses ADH and aldosterone

antidiuretic hormone (ADH)

produced in hypothalamus and released by posterior pituitary gland

causes principal cells of collecting ducts to insert aquaporins in apical membranes, increasing water reabsorption 

increased levels cause an increase in water reabsorption

aldosterone

produced in adrenal glands and released by adrenal cortex

targets collecting ducts (principal cells) and distal DCT

promotes synthesis of apical Na+ and K+ channels, and basolateral Na+-K+ ATPases for Na+ reabsorption (water follows)

as a result, little Na+ leaves body

without, daily loss of filtered Na+ would be 2%, which is incompatible with life

functions: increase BP and decrease K+ levels

atrial natriuretic peptide reabsorptive capabilities

reduces blood Na+, resulting in decreased blood volume and BP

released by cardiac atrial cells if blood volume or pressure elevated

parathyroid hormone reabsorptive capabilities

acts on DCT t o increase Ca2+ reabsorption

tubular secretion

step 3 of urine formation

is reabsorption in reverse

occurs almost completely in PCT

selected substances are moved from peritubular capillaries out into filtrate 

• K+, H+, NH4+, creatinine, organic acids, and bases

• substances synthesized in tubule cells also are secreted (ex. HCO3-)

important for:

• disposing of substances, such as drugs or metabolites, that are bound to plasma proteins

• eliminating undesirable substances that were passively reabsorbed (ex. urea and uric acid)

• ridding body of excess K+ (aldosterone effect)

• controlling blood pH by altering amounts of H+ or HCO3- in urine

regulation of urine concentration and volume

one main function of kidneys is to make any adjustment needed to maintain body fluid osmotic concentration at around 300 mOsm

osmolality

kidneys produce only small amounts of urine if the body is dehydrated, or dilute urine if overhydrated

accomplish this by using countercurrent mechanism

osmolality

number of solute particles in 1 kg of H2O

1 osmol= 1 mole of particle per kg H2O

body fluids have much smaller amounts, so expressed in milliosmols (mOsm)= 0.001 osmol

countercurrent mechanism

fluid flows in opposite directions in 2 adjacent segments of same tube with hairpin turn

overhydration

produces large volume of dilute urine

ADH production decreases

dehydration

produces small volume of concentrated urine

severe: 99% water reabsorbed

urea recycling and the medullary osmotic gradient

urea helps form medullary gradient by

• entering filtrate in ascending thin limb of nephron loop by fascillitated diffusion

• cortical collecting duct reabsorbs water, leaving urea behind

• in deep medullary region, now highly concentrated urea leaves collecting duct and enters interstitial fluid of medulla

  • urea moves back into ascending thin limb

  • contributes to high osmolality in medulla

diuretics

chemicals that enhance urinary output

ADH inhibitors, such as alcohol

Na+ reabsorption inhibitors (and resultant H2O reabsorption), such as caffeine or drugs for hypertension or edema

loop diuretics inhibit medullary gradient formation

osmotic diuretics: substance not reabsorbed, so water remains in urine; ex. in diabetic patient, high glucose concentration pulls water from body

urinalysis

clinical evaluation of kidney

urine is examined for signs of disease

can also be used to test for illegal substances

assessing renal function requires both blood and urine examination

ex. renal function can be assessed by measuring nitrogenous wastes in blood only

to determine renal clearance, both blood and urine are required

urine chemical composition

95% water; 5% solutes

nitrogenous wastes: urea, uric acid, creatinine

other normal solutes found: Na+, K+, PO4 3-, SO4 2-, Ca2+, Mg2+, and HCO3-

abnormally high concentrations of any constituent, or abnormal components such as blood, proteins, WBCs, and bile pigments may indicate pathology

urine physical characteristics

clear (cloudy may indicate urinary tract infection)

pale to deep yellow from urochrome

• pigment from hemoglobin breakdown

• yellow color deepens with increased concentration

abnormal color (pink, brown, smoky)

• can be caused by certain foods, bile pigments, blood, drugs

urea

from amino acid breakdown

largest solute component

uric acid

from nucleic acid metabolism

creatinine

metabolite of creatine phosphate

urine odor

slightly aromatic when fresh

develops ammonia odor upon standing as bacteria metabolize urea

may be altered by some drugs or vegetables

disease may alter smell

patients with diabetes may have acetone smell to urine

urine pH

slightly acidic (~pH 6, with range of 4.5-8)

acidic diet (protein, whole wheat) can cause drop in pH

alkaline diet (vegetarian), prolonged vomiting, or UTIs can cause an increase in pH

urine specific gravity

ratio mass of substance to mass of equal volume of water (water = 1)

ranges from 1.001 to 1.035 because urine is made up of water and solutes

glycosuria

glucose in urine

caused by diabetes mellitus

proteinuria/albuminuria

proteins in urine

nonpathological cause: excessive physical exertion, pregnancy

pathological (over 150 mg/day) cause: glomerulonephritis, severe hypertension, heart failure, often an initial sign of renal disease

ketonuria

ketone bodies in urine

caused by excessive formation and accumulation of ketone bodies, as in starvation and untreated diabetes mellitus

hemoglobinuria

hemoglobin in urine

various causes: transfusion reaction, hemolytic anemia, severe burns, etc.