Urinary System - chapter 21

major roles of the kidneys

1) filter metabolic wastes from the blood (urea, uric acid, and creatine) and excreted them from our body In urine

2) regulate the blood volume and blood pressure by altering the volume of urine produced an day releasing renin into the blood, which activates angiotensin II promoting vasoconstriction and aldosterone secretion. Maintain blood osmolarity of 300mosmoles/L

3) production of erythropoietin in response to low O2 levels. Erythropoietin stimulates erythrocyte proliferation and maturation in the bone marrow

4) regulate the amount of electrolytes (ie Na, L, Cl,Ca, phosphate) in the blood and extracellular fluid by altering the urine concentration and composition. In addition the kidneys are responsible for activating vitamin D3 calciferol, which promotes Ca absorption in the small intestine

5) regulates the body’s pH by controlling the amount of H+ secreted and HCO3 reabsorbed from the filtrate

6) assits liver detox

ureter

the 30cm smooth muscular tube exiting each kidney from the hilum. It carries urine to the bladder by paristalsis, hydrostatic pressure & gravity

urinary bladder

a hollow, stretchy, muscular organ. It contains two sphincters - internal (non voluntary) and external (voluntary but the ANS can override). It’s capacity is approx 500-1000mL ; at 250 mL you feel like you need to pee

urethra

a smooth muscular tube exiting the base of the bladder. in males it is approximately 20cm and in females approximately 4cm

females are 50x more susceptible to infection

the kidneys

the kidneys are retroperitoneal, and are partially protected by the lower ribs

the kidneys receive blood (20% cardiac output) 1200mL/min, from the renal arteries, which branch directly from the aorta, and return their cleansed blood to the inferior vena cava through the real veins

urine produced in the kidneys travels down the 30cm ureters to the urinary bladder for storage

the kidneys are located posterior to the peritoneum (the connective tissue surrounding the go tract) in the retroperitoneal area between T12 and L3

each kidney is covered by outer renal fascia (dense, irregular CT), inner fibrous renal capsule (dense regular CT) & middle layer of adipose tissue (perinephric fat). Kidneys are suspended by collagen from renal fascia packed at AT

there are no pain receptors within the kidney, pain is only present when there is impingement (pressure) on the renal capsule or ureter

kidney blood flow

blood enters the kidney and is transported by smaller arteries to the outer position of the kidney, called the cortex. The majority of the blood is filtered here

the inner portion of the kidney (medulla) arranged in triangular shaped structures (medullary pyramids), alters the composition of the filtrate & forms urine. The area is susceptible to ischemic damage since it is very metabolically active, & has a low pO2 (due to Na/K pumps and slight arteries-venous diffusion shunt)

the urine drains into calyces collecting ducts in the medulla and eventually passes to the renal pelvis and into the ureters for transport to the urinary bladder

the renal artery branches off the aorta and enters at the renal hilum

the renal vein exits the renal hilum & branches onto the inferior vena cava

path of urine drainage

papillary collecting duct - minor calyx - major calyx - renal pelvis - ureter - urinary bladder

3 wastes eliminated in urine

1) urea - is produced in the liver from amino acid breakdown (21g) involves 2 steps:

• amino acid → ammonia (very toxic to cells)

• ammonia → converted to urea by combining with CO2. Urea, which is less toxic is sent to the kidneys for excretion in the urine

2) creatine - produced in skeletal muscles from breakdown of creatine phosphate, a high energy molecule (1.8g)

creatine phosphate is used to generate ATP in resting muscles, it is sent to the kidneys for secretion

3) uric acid - a waste product of adenine and guanine (RNA) (480g)

the build up and crystalization of uric acid is gout.

kidney stones are composed of calcium, phosphate, uric acid and proteins

homeostasis - water/salt balance

kidneys maintain BP & volume by regulating the water/salt balance of the blood

without kidneys:

• if plasma salt concentrations increase, water will leave tissue fluid and enter capillaries, causing an increase in blood volume and pressure resulting in dehydrated cells

by maintaining appropriate concentration of plasma, blood pressure and volume are kept constant and cells are kept appropriately hydrated

so if blood solute concentration increases the kidneys absorb excess salts (Na, K, Ca) and excrete the excess salts in urine to maintain homeostasis. Likewise the kidneys remove excess water from plasma to maintain water/salt homeostasis and maintain normal BV and pressure

homeostasis - acid-base balance of blood

kidneys monitor H+, OH and HCO3 ion concentrations in order to maintain constant blood pH of 7.4

if blood becomes acidic the kidneys excrete H+ ions and reabsorbs the HCO3 into the bloodstream. This is the most common as all cells create acid byproducts due to cellular respiration (CO22 conversion to H2CO3 in blood). Therefore average pH of urine is 6.0

If blood becomes basic the kidneys excrete excess HCO3 ions and reabsorb the H+ ions into the bloodstream

the nephron

the urine producing apparatus in the kidney

the nephron consists of a glomerulus, that filters the blood and forms a filtrate, and a tubule, that converts the filtrate into urine by reabsorbing water and electrolytes from filtrate

the tubule has 3 regions

teh proximal convoluted tubule, 2) loop of henle, which enters into the medulla of the kidney and 3) the distal convoluted tubule

the distal convoluted tubule drains into a common collecting duct that makes some final modifications to the urine and ultimately transports the urine into the ureters

85% are cortical, 15% are juxtamedullary nephrons

kidneys can produce urine 4x more concentrated than plasma

blood supply to the nephron

blood flows into the glomerulus through the afferent arteriole, which divides into the glomerular capillaries

these capillaries are very plus and allow large amounts of blood plasma to filter out into the glomerular capsule and into the proximal tubule

blood leaves the glomerulus through the efferent arteriole, which divides into the peritubular capillaries. These capillaries surround the tubule and function to absorb water and electrolytes from the filtrate (tubular fluid)

3 processes used to produce urine

1) filteration - water and dissolved solutes smaller than 8nm (urea, glucose, salts) are filtered through the glomerular capillaries and into the tubule

2) reabsorption - 99% of water, glucose, amino acids, fatty acids, vitamins and selected electrolytes are transported into the tubular cells and enter into the peritubular capillary blood

3) H+,K+, some metabolic wastes and drugs are secretes from the tubular cells into the tubular fluid

the glomerulus

the glomerular capillaries are formed from the afferent arteriole

like most capillaries, the glomerular capillaries are comprised of endothelial cells, however these have pores called fenestrations & are covered by pedicels of epithelial cells called podocytes

the fenestrations only allow particles less than 8nm to pass; however the capilariy basement membrane (laminate dense) contain collagen & negatively charged proteoglycan. This effectively repels other anions, like the protein albumin

molecules permitted - water, glucose, vitamins, amino acids, peptides, ammonia, urea, creatine and ions

not permitted - WBC, RBC, platelets, and proteins

control of filtration

glomerular capillaries are 50x leakier than other capillaries (even leakier than fenestrated because they lack a diaphragm)

glomerular pressure is high, because the diameter of efferent arterioles is smaller than afferent arterioles

glomerular capillaries have a large surface area

• the amount of SA available is regulated by the contraction of mesangial cells; when mesangial cells are relaxed, filtration slit SA in increased and there for GFR (glomerular filtration rate) is increased

renal blood pressure

blood to the kidney is regulated to maintain filtration, & not to satisfy the metabolic needs of the tissue. At rest the kidneys receive 25% of the cardiac output (1.2 L/minute) . These increased with exercise

the blood pressure in the glomerular capillaries is 55 mmHg. This high pressure is maintained by flow through the afferent arteriole (BFg) and high resistance to flow in the efferent arteriole (Rg). The glomerular blood pressure (BPg) id the driving force to create filtration and is determined by: BPg = BFg x Rg

where BFg is increased with afferent arteriolar dilation and decreased with constriction, and Rg is increased with efferent constriction and decreased with dilation

when BPg is increased, filtration is increased, and when BPg is decreased, filtration is decreased

glomerular filtration rate

filtration through the glomerular capillaries is governed by the same forces as any other capillary in the body

• blood hydrostatic pressure pushes fluid out and the colloid osmotic pressure pushes fluid into the capillary

• the glomerulus capillaries are fenestrated to increase their permeability, also the blood pressure is high compared to other capillaries

the glomerular filtration rate is the amount of blood plasma filtered through the capillaries by both kidneys in one minute (125mL/min)

GFR is regulated primarily by altering the glomerular blood pressure (BPg). Increasing flow through the capillaries (afferent constriction) increases GFR

where as decreasing flow and decreasing resistance would decrease GFR

why is CHP different than IHP

Capillary hydrostatic pressure is higher because of back pressure (elastic recoil from capsule). due to the glomerulus being in a contained space

if there a difference in filtrate produced depending on gender

150L for female

180L for male

due to difference in body size

The renal tubule

the renal tubule is responsible for reabsorbing glucose, amino acids, water & electrolytes from filtrate (tubular fluid)

other substance (K+) may be secreted into the tubular fluid

reabsorption and secretion may occur passively or by active process

passive processes may include diffusion and osmosis; where as active processes require ATP either directly (primary active) or indirectly (secondary active or co transport)

180L/day of water is filtered through the glomerulus and the normal urine volume is only 1L/day. Therefor, more than 99% of filtrate is normally reabsorbed

The proximal tubule

most reabsorption in the proximal tubule is transcellular & occurs by Na co transport

a Na concentration gradient is created by the Na/K pump on the basal surface of the tubule called

this gradient is used to power the absorption of other molecules like glucose

the glucose transporter is called the sodium dependent glucose transporter (SGLT, sodium glucose linked transporter)

Cl ions diffuse passively through Cl- channels and paracellular route (through not so tight junctions) to maintain electrochemical neutrality

60-70% of water is reabsorbed in the PCT, the osmotic gradient created by reabsorption of solutes. Water passes the plasma membrane through pores created from the protein aquaporin-1 and also use paracellular route

Transport maximum

Tg

65mg/dL amino acids. 180mg/dL glucose, low for water sol-vitamins

the loop of henle

the primary function os to remove water from filtrate

this is achieved by a highly concentrated interstitial fluid (ISF) that becomes more concentrated deeper into the medullary pyramid. This concentration gradient in maintained by the vasa recta

as filtrate decends into the loop, water is pulled out by osmosis because of the ISF concentration

the loss of water creates a highly concentrated filtrate. As the filtrate ascends the loop Na and Cl are actively reabsorbed to reduce the filtrate concentration. Osmotic concentration (solute particles/L goes from 300 to 100Osm)

the net result is a greatly diminished filtrate volume

depending and ascending loop

thin depending limb - permeable to water, impermeable to solutes

thick ascending limb - impermeable to water, active solute transport

active transport of NaCl along the ascending thick limb results in the movement of water from the descending limb

papillary duct - permeable to urea

the permeability of both the collecting duct and the loop tend to concentrate urea in the tubular fluid and in the medulla.

The nephron loop DCT and collecting duct and impermeable two urea. As water reabsorption occurs, the urea concentration rises

sodium potassium pump in loop of henle

the mechanism of sodium and chloride ion transport involves the Na+ - K/2Cl carrier at the apical surface and 2 carriers at the basal surface of the tubular cell: a potassium - chloride cotransport pump and a sodium-potassium exchange pump. The net result is the transport of sodium and chloride ions into the peritubular fluid

concurrent vs counter current flow

kidneys use countercurrent flow to remove water from urine so the body can retain water used to move nitrogenous waste products

a countercurrent multiplier system where a high medullary interstitial concentration of solute is maintained allowing the kidney to concentrate urine

the loop of henle is the counter current multiplier actively pumping out NaCl in ascending limbs

a positive feedback loop is created as NaCl removal “pulls” water out of descending limb increasing NaCl concentration, which then is actively pumped out

the vasa recta is the counter current exchanger

the vasa recta is a portion of the peritubular capillary system which enters the medulla. If the vasa recta did not exist the high concentration of solutes in the medullary interstinium would be washed out

types of intercalated cells and principal cells

type A intercalated - secrete hydrogen, reabsorb HCO3

type B intercalated - secrete HCO3, reabsorb hydrogen (H)

principle - secrete K, reabsorb H2O

aldosterone and ADH

both aldosterone and ADH (vasopressin) exert the majority of their effects on the collecting ducts the kidneys

Aldosterone is released from the adrenal cortex in response to angiotensin II, it increases the production of epithelial sodium channel (ENaC). This increases the sodium absorption from the collecting duct, water follows osmotically through aquaporin-1

ADH is released by the posterior pituitary in response to high extracellular fluid osmolarity or low BP. ADH causes a a vesicle bound aquaporin-2 to move to the plasma membrane and increase the absorption of water

renal control of acid base status

The proximal tubule cells utilize the enzyme carbonic anhydrase to help regulate the body’s pH

this enzyme converts CO2 and H2O into H+ HCO3, and visa versa

CO2 from the peritubular capillaries for from filtered HCO3 is converted into H and HCO3 within the cells

H+ is then secreted into the filtrate through the Na+/H exchanger, while HCO3 is reabsorbed

This system is regulated by the pCO2 in peritubular capillaries - if pCO2 is elevated, more H+ is secreted and HCO3 absorbed.

• K+ tends to be conserved when more H+ is secreted. If pCO2 is decreased, less H+ is secreted and HCO3 absorbed

glomerular filteration rate

amount of filtrate both kidneys produce each minute

averages 125mL/min

about 10% of fluid delivered to kidneys leaves blood stream to become filtrate this is the basis of kidney function (health) tests

net filtration pressure (-10mmhg) determines GFR

• if GHP drops from 50mmHg to 40mmHg then NFP=0 and GFR will be zero (no kidney filtration)

hypotension can cause cause a drop in GBHP

• caused by hemorrhaging, heart attack, dehydration

if renal flow & GFR not restored, will lead to acute renal failure

creatine Clearance tests

compare the amount eliminated in urine with plasma concentration

ex: patient A: 84mg/h in urine and plasma creatine conc. is 1.4mg/dL, so

84/1.4 = 60dL/hr= 100mL/min

importance in maintaining GFR

the body needs to keep GFR of 125mL/minute to maintain adequate filtration of blood

GFR changes throughout the day

• will increase if BP or BV increase (BP increase during exercise or stress, BV increase If over hydrated)

• will decrease if BP or BV decreases (BP decreases in sleep and BV decreases if dehydrated)

body controls GFR using autoregulation, hormonal regulation and autonomic regulation

neural regulation

renal nerves

• innervate kidneys & ureters (most are sympathetic nerves)

• enter each kidney at hilum

• follow branches of renal arteries to individual nephron

sympathetic innervation

1. adjusts rate of urine formation by changing blood flow and afferent and efferent arterioles

2. influences urine composition by stimulating release of renin

autoregulation

maintains adequate GFR despite changes in local blood pressure & blood flow

myogenic

involves changing luminal diameters of:

• afferent arterioles - if renal BP increases, afferent vessel wall stretch induces smooth muscle to contract, causing vasoconstriction. If this doesn’t happen GHP will be too high & GFR will be too high

• efferent arterioles maintain tone that is narrower that afferent arteriole so that kidneys GFR is 125mL/min

• glomerular capillaries - if GFR is too high, intraglomerular mesangial cells contract to decrease both glomerular capillaries diameter & filtration slit size = decreased GFR

intraglomerular control diameter of glomerular capillaries and size of filtration slits. Also provide glomerular support (and capable of phagosizing debris) - made up of modified smooth muscle (actin)

hormonal regulation

activation of the Juxtaglomerular complex which is composed of

• macula dense epithelia cells of DCT, near renal corpuscle (function as chemoreceptors or baroreceptors)

• juxtaglomerular cells - smooth muscle cells in afferent arteriole wall (function as baroreceptors and secrete renin & EPO), generate tubuloglomerular feedback

• extraglomerular mesangial cells - located between afferent artioles, provide feedback control , but exact function is unclear

activation of RAAS (renin-angiotension-aldosterone system)

how does JGc help control urine concentration

also helps control BP and BV

1- the macula dense is part of the distal convoluted tubule & senses Na and Cl conc. changes in the filtrate, & can dilate or constrict the arterioles appropriately

1 - a decrease in BP or BV causes a decrease in GFR resulting in less filtration and a decrease in salt conc. in the filtrate (because there is more time for reabsorption)

2- the macula dense will sense this then:

• trigger dilation of affront arteriole to increase GFR

• trigger the juxtaglomerular cells lining the affront arteriole to produce & release renin. JG cells function as baroreceptors and can also release renin independently of the macula densa

2 - The (granular) juxtaglomerular cells secrete EPO & renin in response to low BP or macula densa or SNS stimulation

• EPO stimulates maturation of RBC ‘s, which increases BV and BP

• Renin catalyzes the activation of angiosten I, which is converted to angiosten II. Ang. II stimulates ADH & aldosterone increases H2o & NaCl reabsorption into the blood. This increases BV & BP, vasoconstriction increases BP

Juxtaglomerular apparatus

made up of 3 cell types

1. extraglomerular mesangial cells

2. macula densa cells

3. juxtaglomerular cells

Regulating MAP affects GHP & GFR

GFR can be overridden by SNS and RAAS

normally autoregulation can alter GHP to keep GFR constant however

if hemorrhaging - BP is very low (less than 80mmHg ) then blood will be shunted to vital organs and even lower renal blood flow and pressure may occur- which will damage kidneys if not rectified

ANP and BNP

they can both override autoregulation (myogenic & JGC) during extreme events (eg, hyponatremia due to over hydration)

Micturition sacral reflex

1 - stretch receptors in the bladder are activated & output is activated by sensory neurons to spinal cord, cerebrum & pons

2- PSNS nerves are stimulated and cause bladder detrusor muscle to contract (normally a sympathetic tone causes relaxation of detrusor and contraction of internal sphincter). normally voluntary motor neuron has constant tone stimulating contraction

3 - cerebrum determines if location is appropriate then stimulates pons to inhibit sympathetic output to detrusor & internal sphincter. Voluntary motor neuron to external sphincter stops firing so sphincter relaxes