The urinary system –part 1-functional anatomy-

-urinary system functions--filtration process and GRF-

Denise Zahiu, MD PhD

The urinary system (renal system) consists of the kidneys, ureters, bladder and the urethra

• Urine is formed in the kidneys through filtration of blood.

• The urine is then passed through the ureters to the bladder, where it is stored.

• During urination, the urine is passed from the bladder through the urethra, outside the body.

• The human kidneys are paired, bean-shaped structures that lie behind the peritoneum on each side of the vertebral column (extending from the 12th thoracic vertebra to the 3rd lumbar vertebra).

Urinary system functions

The kidney:• produces urine by filtering and excreting metabolic products and toxins

from the blood

• regulates the body's fluid status and the electrolyte balance by adjusting water and electrolyte excretion to match the intake of fluids and ions.

• regulates acid-base balance by excreting H+ and by regulating the plasmatic buffer stores (HCO3-).

• produces or activates hormones that are involved in

erythrogenesis (erythropoietin)

Ca2+ metabolism (1,25-(OH)2vitamin D3=calcitriol)

the regulation of blood pressure and blood flow by excreting variable amounts of water and Na+ or/and by secreting vasoactive factors and renin

The ureters– pathways for the urine excretion

• The ureters propel urine from the renal pelvis to thebladder by peristaltic waves conducted along asyncytium of smooth muscle cells.

• Reflux of urine back into the ureters duringcontraction of the bladder is prevented by theureter’s oblique pathway through the bladder walland by a flap-like valve of mucous membrane thatcovers each ureteral orifice.

• As the bladder fills, the intraparietal segment of theureter is compressed.

Urinary system functions

A, A refluxing ureterovesicaljunction has the same anatomicfeatures as a nonrefluxing orifice,except for inadequate length of theintravesical submucosal ureter.

Urinary system functions

The bladder –stores and intermittently excretes the urine (micturition)

!! Bladder outlet = internal sphincter

Storage function of the bladderDuring the storage phase, stretch receptors inthe bladder send afferent signals to the brain through the pelvic splanchnic nerves. Pelvic-hypogastric reflex facilitates bladder filling.

• urge for voluntary bladder emptying ~150 mL • fullness - 400 to 500 mL.

Nevertheless, until a socially acceptable opportunity to void presents itself, efferent impulses from the brain, in a learned reflex, inhibit presynaptic parasympathetic neurons in the sacral spinal cord and contracts the external urethral sphincter by activating the pudendal nerve (the guarding reflex)

Stretch receptors = R

β3-R

Nicotinic -R

Hypogastric nerveT11-L2

S2-S4

Contracts the external urethral sphincter (somatic fb.)

Sympathetic fb.

Cortical centers

α1-R

β3-R

• The voiding phase begins with a voluntaryrelaxation of the external urinary sphincter,followed by the internal sphincter.

• The pontine centers no longer inhibit theparasympathetic preganglionic neurons thatinnervate the detrusor muscle. As a result, thebladder contracts and the internal urethralsphincter relaxes, expelling urine.

• The basic bladder reflex (inherently anautonomic spinal cord reflex), may be eitherfacilitated or inhibited by higher centers in thecentral nervous system

Micturition reflex

Parasympathetic fb

Muscarinic 3-R

• The renal hilus—serves as the portof entry for the renal artery andnerves and as the site of exit forthe renal vein, the lymphatics, andthe ureter.

• The renal sinus includes the urine-filled spaces: the renal pelvis, themajor and the minor calyces.

• Kidney layers:

Cortex –granular aspectdue to thepresence of glomeruli

Medulla –parallel arrangement oftubules and small blood vessels; itis divided in 8-18 renal pyramids

Kidney anatomy

• Each kidney consists of ~1 million of nephrons.

• A nephron consists of a renal corpuscle and a tubule.

• The renal corpuscle comprises a glomerulus, Bowman's space, Bowman's capsule • The subdivisions of the tubule are: the proximal tubule the thin descending and thin ascending

limbs of the loop of Henlethe thick ascending limb of the loop of

Henle, the distalconvoluted tubulethe connecting tubule.

The functional unit of the kidney is the nephron

• Superficial nephrons (cortical nephrons) -have short loops extending to the boundary between outer and inner medulla.

• Juxtamedullary nephrons - have long loops that extend as far as the tip of the medulla.

They play a special role in the production of concentrated urine.

There are two types of nephrons

Renal circulation receives ~20% of the cardiac output.This high blood flow provides the blood plasma necessary for forming an ultrafiltratein the glomeruli.

*90% perfusessuperficial glomeruli*10% perfusesjuxtamedullaryglomeruli and medulla.

Main features of the renal vascular system

• The renal circulation has a unique sequence of vascular elements:

• the afferent arteriole - a high-resistance arteriole

• high-pressure glomerular capillary network for filtration,

• the efferent arteriole - a second high-resistance arteriole

• peritubular capillaries - a low-pressure capillary network that surrounds the renal tubules and takes up the fluid absorbed by these tubules.

Renal circulation

• Vasa recta are the efferent arterioles of juxtamedullarynephrons that descend into the renal papillae.

• They form hairpin-shaped vessels, which provide capillary networks for tubules in the medulla.

Renal circulation Renal cortex

Medulla

Vasa recta

Arcuate vessels

How does the urine forms?

The nephron forms an ultrafiltrate of the bloodplasma and then selectively reabsorbs the tubule fluid or secretes solutes into it.

The renal corpuscle is the site of formation of the glomerular filtrate.

• The mesangial cells:

can contract

support the capillary network,

secrete the extracellular matrix

are continuous with the smooth muscle cells of the afferent and efferent arterioles

• Podocytes:

are modified epithelial cells

their foot processes cover the glomerular capillaries

they are continuous with the parietal layer of Bowman’s capsule

Renal corpuscle structure - glomerulus

The glomerular filtration barrier has four elements:

1. the glycocalyx covering the luminal surface of endothelial cells - negatively charged glycosaminoglycans2. the endothelial cells – contain large fenestrations, 70-nm holes that provide restriction to the filtration of cellular elements3. the glomerular basement membrane- restricts intermediate-sized to large solutes (molecular weight >1 kDa)-contains heparan sulfate proteoglycans, so it is especially restricts large, negatively charged solutes4. podocytes- have foot interdigitating processes that cover the basement membrane- between the interdigitations are filtration slits

Inner aspect of glomerular capillaries,showing fenestrations of endothelial cells(arrows).

*Some of the proteins of the slit membrane may

recruit other molecules involved in signaling

events that control slit permeability

*In Finnish-type nephrosis, the genetic absence of

nephrin leads to severe proteinuria

What are the substances that can filter?

*Dextran is a complex branched polysaccharide, used as an antithrombotic (antiplatelet) or as a volume expander in hypovolaemia.

What are the substances that can filter?

Starling forces involved in the glomerular filtrationGlomerular filtration is a process consisting in the movement of water and small molecules from the glomerular capillaries to the Bowman’s space, due to differences in pressure.Quantitatively, the rate of filtration that occurs in the glomeruli greatly exceeds that in all the other capillaries of the circulation combined because of greater Starling forces and higher capillary permeability.

Glomerular filtration rate (GRF) – an important renal parameter

• GFR = the volume of fluid filtered into Bowman’s capsule per unit time.

• The glomerular filtrate is the product of glomerular filtration, is a protein free plasma.

• GRF = 125 ml/min = 180 L/day

!

Determinants of GRF

*PG= hydrostatic glomerular pressure*PB hydrostatic pressure in Bowman’s capsule*πG = colloid-osmotic pressure in the glomeruliKf= a filtration constant

Determinants of GRF

Why severe constriction of efferent arteriole decreases GRF?

The juxtaglomerular apparatus (JGA) is part of a complex feedback mechanism that regulates renal blood flow and filtration rate • extraglomerular mesangial cells

• the macula densa - a region of specialized epithelial cells of the thick ascending limb, where it contacts its glomerulus

• the granular cells (called juxtaglomerular or epithelioid cells) are in the wall of afferent arterioles are specialized smooth muscle cells that produce, store, and release renin

Sympathetic Nerves effects on GRF

• At relatively high levels of nerve stimulation, both afferent and efferent arteriolar resistances rise, thus generally decreasing RBF and GFR.

• The RBF may fall more than the GFR is consistent with a preferential efferent arteriolar constriction.

• With maximal nerve stimulation, however, afferent vasoconstriction predominates and leads to drastic reductions in both renal blood flow and GFR.

• triggers granular cells to increase their release of renin, raising levels of ANG II

Atrial Natriuretic Peptide (ANP)

• Released by atrial myocytes in response to increased atrial pressure and thus effective circulating volume, ANP markedly vasodilates afferent and efferent arterioles, thereby increasing cortical and medullary blood flow, and lowers thesensitivity of the tubuloglomerular feedback mechanism .

• Also, it inhibits secretion of renin (thus lowering ANG II levels).

The net effect is an increase in GFR.

Clinical estimation of GRF

Serum creatinine mg% Percentage of functional nephrons %

1,52468

1114

50301510851

Cockroft- Gault Equation

MDRD – calculator (Modification of Diet in Renal Disease)

Clinical case

• M.B. , 78-years old women, was brought to the emergency room for red blood in her stools. This symptom was present for more than 48h, so she could no longer ignore it.

• She doesn’t smoke or drink alcoholic beverages.

• She takes aspirin or diclofenac for arthritis, sometimes more than 3 tablets daily.

• In the emergency room the patient was light-headed, pale, cold and vey anxious.

• Her hematocrit was 29% (N 36-46%). Blood pressure was 90/60 mmHg and the heart rate 105 beats/min lying down. In the upright position she had BP 75/45 mmHg and 135 beats/min.

• During the last 24 hours , her urinary volume was only 400 ml despite a fluid oral intake of 2L.

1. What is the diagnosis of this patient?

• Gastrointestinal hemorrhage with hypovolemic shock.

• Shock (circulatory shock) is a condition in which decreased blood flow causes decreased tissue perfusion an O2 delivery. Untreated shock can lead to impaired tissue and cellular metabolism and, ultimately, death.

• Hypovolemic shock occurs when circulating volume is decreased because of loss of whole blood (hemorrhagic shock), loss f plasma volume (burn), or loss of fluid and electrolytes (vomiting, diarrhea)

• Shock is defined by mean arterial pressure less than 60 mmHg

For BP 75/45 mmHg, mean arterial pressure is 55 mmHg

2. The patient had a significant lost of volume of whole blood. How did this blood loss lead to decreased arterial pressure? Blood pouring out of arteries

Decreases the venous return to the heart and a decreased end-diastolic volume (cardiac filling pressure decreases)

Cardiac output decreases

Arterial pressure = cardiac output x total peripheral resistance (TPR)Therefore arterial pressure decreases

3. Why was the patient arterial pressure lower in the upright position than in the lying position?• Arterial pressure was lower in upright position than in supine position

because when she was upright the venous return was further reduced by the gravity (blood pooled in the veins of her legs)

4. Her heart rate was elevated. Why?The heart rate was elevated as a compensatory mechanism to hemorrhage.Cardiac output = stroke volume x heart rateThe baroreceptor reflex activates sympathetic system and as a result heart rate increases.*The sympathetic system increases also the total peripheral resistance by arteriolar vasoconstriction mediated through alpha-adrenergic receptors.Arterial pressure = cardiac output x total peripheral resistance (TPR)

5. In our patient, the glomerular filtration rate is normal, decreased or increased?• GFR is decreased as a result of decreased renal blood flow, so a lower

hydrostatic glomerular pressure.

6. What other compensatory mechanisms were activated by the hemorrhage?• An other mechanism is the release of renin by the kidney.

• Renin is released in response to:

A decrease in arterial blood pressure as detected by the pressure-sensitive cells, the granular cells located in the walls of afferent and efferent arterioles. This is the most direct causal link between blood pressure and renin secretion (the other two methods operate via longer pathways).

Sympathetic nervous system activity, which also controls blood pressure, acting through the β1 adrenergic receptors.

A decrease in sodium load delivered to the distal tubule. This load is measured by the macula densa of the juxtaglomerular apparatus.

The low GFR determines a lower flow of ultrafiltrate, so a greater reabsorbtion of Na will occour in the proximal convoluted tubule. Macula densa will sense the lower Na+ load and will stimulate the secretion of renin by the granular cells.

The renin enzyme circulates in the blood stream and hydrolyzes angiotensinogen secreted from the liver into the peptide angiotensin I.

Angiotensin I is further cleaved in the lungs by endothelial-bound angiotensin-converting enzyme (ACE) into angiotensin II, the most vasoactive peptide

6. What are the effects of compensatory mechanisms on GFR?

Both sympathetic activity and angiotensin II causes arterial vasoconstriction. In the kidneys, there are endogens modulators of renal vasoconstriction. Prostaglandins E2 and I2 are renal vasodilators acting on the afferent arteriole. Their production is induced by angiotensin II and sympathetic activity.

Renal blood flow is protected and maintained in high vasoconstrictor states, such as hemorrhage

7. Does your patient may continue to take the drugs for arthritis?

No, she may not. Nonsteroidal anti-inflammatory drugs, like aspirin and diclofenac, are cyclooxygenase inhibitors that block prostaglandin synthesis. Therefore, the patient would be at risk for developing renal failure.