Urinary system

Introduction GF Tubular reabsorption Tubular secretion Urine excretion & plasma clearance

functions
1- maintaining ECF stability volume & compsoition 2- main route for eliminating potentially toxic wastes & foreign compounds from the body 3- acid-base balance 4- producing erythropoiten 5- producing renin which triggers a chain reaction important in salt conservation by kidneys 6- converting vitamin D into its active form

Kidneys: urine forming organs, beanshaped, located in the back of the abdominal wall Renal pelvis: central collecting cavity that leads to the ureter which is a smooth muscle walled duct Urinary bladder: smooth muscle walled sac that stores urine Urethra: straight and short in female, long and curving course in males passing through the prostate gland and the penis

Nephron: the functional unit, 2 million in both kidneys: a- medullary b- cortical vascular components of the nephron : 1- Glomerulus : ball like tuft of capillaries 2-afferent arteriole to the glomerulus 3-efferent arteriole out of the glomerulus 4-peritubular capillaries then venules

Tubular components of the nephron: -hallow fluid filled tube, single layer of epithelium 1-Bowman's capsule around the glomerulus 2-proximal tubule convoluted 3-loop of Henle: u-shaped, dips into the medulla: a-descending b-ascending passes between the afferent & efferent arterioles 4-distal tubule: lies in the cortex 5-collecting duct: 8 nephrons drain in one duct

Proximal tubule Juxtaglomerular apparatus Efferent arteriole Afferent arteriole

Distal tubule

Collecting duct

Bowmans capsule Artery Vein Glomerulus

Cortex Medulla

Peritubular capillaries

Loop of Henle To renal pelvis

Fig. 13-2, p. 408

Overview of Functions of Parts of a Nephron

Glomerular filtration

Plasma free from protein filters in b. capsule 20% of plasma that enters the glomerulus is filtered 125mL of glomerular filtrate is formed each minute ( 180L/day) kidneys filter the entire plasma volume 65 times/day Glom. Membrane: a-wall of glom. Capillaries is 100x more permeable b-basement membrane: acellular gelatinous layer c-inner layer of B. capsule is made of podocytes which are octopus like cells between filtration slits

Capillary pore

Endothelial cell
Lumen of glomerular capillary

Basement membrane

Lumen of Bowmans capsule Filtration slit

Podocyte foot process

Fig. 13-5c, p. 410

Afferent arteriole Glomerulus

Efferent arteriole

GF
Bowmans capsule

80% of the plasma that enters the glomerulus is not filtered and leaves through the efferent arteriole.
TR Peritubular capillary

20% of the plasma that enters the glomerulus is filtered.

TS

Kidney tubule (entire length, uncoiled) Urine excretion (eliminated from the body)

To venous system (conserved for the body)

Fig. 13-4, p. 409

Afferent arteriole

Efferent arteriole

Glomerulus

Bowmans capsule Lumen of Bowmans capsule

Lumen of glomerular capillary Endothelial cell Basement membrane

Outer layer of Bowmans capsule Inner layer of Bowmans capsule (podocytes) Proximal convoluted tubule

Podocyte foot process

(see next slide)

Fig. 13-5a, p. 410

Forces involved in GF

Like forces starling capillary circulation with 2 exceptions: a- permeability is much higher b- filtration occurs through out the whole glomerulus capillary

1- glomerulus blood pressure ~55mmHg larger than any other capillary because the afferent arteriole are wide and the efferent are narrow 2-plasma colloid osmotic pressure ~30mmHg, opposes filtration 3-Bomans capsule hydrostatic pressure ~15mmHg exerted by the fluid in the initial part of the tubule, opposes filtration

Table 13-1, p. 412

GFR

Net filtrating pr. = 55- (30+15)= 10mmHg Changes in GFR occurs mainly due to changes in the glom. capillary pr. By the sympathetic effect mainly on the afferent arteriole not the efferent one decreased BP carotid & aortic baroreceptors increase symp. vasoconstriction afferent spasm decrease bl. Flow decrease glom. Cap. Pr. decrease GFR decrease urine conserve body fluid & salts increase BP

GFR
increased BP carotid & aortic baroreceptors decrease symp. vasodilatation afferent dilatation increase bl. Flow increase glom. Cap. Pr. increase GFR increase urine decrease body fluid decrease BP

Glomerulus

Afferent arteriole

Glomerular capillary blood pressure

Efferent arteriole

Vasoconstriction (decreases blood flow into the glomerulus)

Net filtration pressure

GFR

Fig. 13-8a, p. 413

Glomerulus

Afferent arteriole

Glomerular capillary blood pressure

Efferent arteriole

Net filtration pressure

Vasodilation (increases blood flow into the glomerulus)

GFR

Fig. 13-8b, p. 413

Short-term adjustment for

Arterial blood pressure Detection by aortic arch and carotid sinus baroreceptors Sympathetic activity Generalized arteriolar vasoconstriction Afferent arteriolar vasoconstriction Glomerular capillary blood pressure

Long-term adjustment for

Arterial blood pressure Cardiac output

Total peripheral resistance

GFR

Urine volume

Conservation of fluid and salt

Arterial blood pressure

Fig. 13-7, p. 413

22-25% of the cardiac output goes to the kidneys ( 1140mL/min) and Htc. accounts for 45% so the kidney receives 625mL plasma/min and 20% of those are filtrated (125mL)(GFR)

Tubular reabsorption
Tremendously & highly selective & has a high reabsorptive capacity for needed materials Little capacity for wastes & no capacity for toxics 125mL/min GFR 124 ml is reabsorbed (99% H2O, 100% glucose, 99.5% salts) Steps of transepithelial transport: 1-luminal membrane 2-cytosol 3-basolateral mem. 4-interstitial 5-capillary wall

Passive transport and active transport : active if one step is active -3 + -glucose, AA, organic nutrients, Na, PO4 Na reabsorption: Na-K pump at basolateral membrane is essential for Na reabsorption(99.5%): -67% in proximal tubules -25% in loop of henle -8% in collecting & distal tubules -in proximal tubules Na reabsorption helps in glucose, AA, H2O, Cl, and urea reabsorption.

Na reabsorption

in the ascending limb of the loop of henle Na reabsorption along with Cl play a critical role in producing urine of varying concentration and volume Theres no Na reabsorption in the descending limb of loop of henle In the distal & collecting tubules Na reabsorption is variable & subject to hormonal control, and it plays a role in regulating ECF volume and links with K & H secretion Na is firstly absorbed by the Na-K pump in the basolateral wall then from the lumen in cells by passive transport

Lumen

Tubular cell

Interstitial fluid

Peritubular capillary

Diffusion Na+ channel

Active transport

Basolateral Na+ K+ ATPase carrier

Lateral space

Diffusion

Fig. 13-10, p. 416

Glucose reabsorption

Proximal tubules with glucose cotransport and AA almost 100%, then by facilitated passive transport in the basolateral wall, Naglucose carriers as well as Na-AA are specific -those carriers has a maximum transport capacity called tubular maximum (Tm) -any quantity beyond Tm will escape into urine -filtered load= plasma con. x GFR for glucose= 100mg/100mL x 125mL/min

Glucose reabsorption
-Tm for glucose averages 375mg/min -the plasma con. Of glucose at which glucose reaches its Tm is called renal threshold (300mg/100mL) -if glucose plasma con. Increases it will leave the filtrate -if glucose plasma con. decreases it will be completely reabsorbed -kidneys do not regulate glucose and AA

Fig. 13-12, p. 420

Phosphate & calcium reabsorption

Both are actively absorbed and regulated by the kidneys The renal threshold for both of these substances equals to their plasma con. -the tubules will reabsorb the same normal plasma con. And any excess that is ingested will be spilled out in the urine restoring the normal plasma con. +2 -3 - PO4 & Ca renal threshold can be regulated by the parathyroid hormone depending on the body needs

aldosterone
Aldosterone stimulates Na reabsorption in the distal and collecting tubules -if Na con. In plasma is high no regulation Na out -if Na con. In plasma is low aldosterone release more reabsorption conserve Na Renin-angeotensin-aldosterone system (RAAS): -renin is secreted from the juxtaglomerulus apparatus which activates the angiotensin in the plasma into angiotensin I -angiotensin I under the effect of ACE in the pulmonary circulation is converted to angiotensin II which stimulates aldosterone release

NaCl /

ECF volume /

Arterial blood pressure

Liver

Kidney

Lungs

Adrenal cortex

Kidney

H2O conserved

Na+ (and CI) osmotically hold more H2O in ECF

Renin

Angiotensinconverting enzyme

Na+ (and CI) conserved

Angiotensinogen

Angiotensin I

Angiotensin II

Aldosterone

Na+ reabsorption by kidney tubules ( CI reabsorption follows passively)

Vasopressin

Thirst

Arteriolar vasoconstriction

H2O reabsorption by kidney tubules

Fluid intake

Fig. 13-11, p. 417

aldosterone effects: -promotes insertion of new Na channels into the luminal membrane -additional Na-K carriers in the basolateral membrane -these effects are seen in the distal & collecting tubules When Na load, ECF/plasma volume, and BP are above normal renin release is inhibited no aldosterone Na portion in the distal tubules and the collecting ducts is excerted 8% is not a small amount considering the fact that per day plasma will be filtered 65 times so 20g of salt is lost per day

Na+/ ECF volume/ arterial pressure

Renin

Angiotensin I

Plasma K+

Angiotensin II

Aldosterone

Tubular K+ secretion

Tubular Na+ reabsorption

Urinary K+ excretion

Urinary Na+ excretion

Fig. 13-15, p. 423

ANP (atrial natriuretic peptide)

ANP is released from the atria when the heart is stretched by expansion of the ECF volume as a result of Na & H2O retention -increased BP ANP release inhibit Na reabsorption more Na & H2O are released into the urine less ECF volume decrease BP

Table 13-3, p. 424

Cl reabsorption

Passively absorbed down the electrical gradient which is created by active Na reabsorption

H2O reabsorption

Passive by osmosis following Na reabsorption - 65% (117L/day) by the end of the proximal tubules - 15% of filtered H2O is obligatorily reabsorbed from loop of henle - 20% remaining is reabsorbed in distal tubules Hormonal regulation: -water channels in the aquaporins part is regulated by vasopressin

Urea reabsorption

Passive linked to active Na reabsorption In the proximal tubules [urea] is increased three time because of Na & H2O reabsorption Urea is passively absorbed but it does not have good permeability only 50% of urea is reabsorbed

Glomerulus Bowmans capsule Peritubular capillary 125 ml of filtrate

Beginning of proximal tubule

Na+ (active) H2O (osmosis)

Na+ (active) H2O (osmosis) End of proximal tubule 44 ml of filtrate

= Urea molecules

Passive diffusion of urea down its concentration gradient

Fig. 13-13, p. 421

wastes

Waste products are not reabsorbed because the permeability of the tubules to these products is almost zero : -phenol -creatinine -other toxics

Tubular secretion

Supplemental mechanisms that hasten elimination of substances from the body

1- hydrogen: - important for acid-base balance - secreted by proximal, distal, & collecting tubules

2- potassium: -actively reabsorbed in proximal tubules

-actively secreted in distal & collecting tubules -when plasma [K] increases, secretion is adjusted to eliminate K out

-mechanism of secretion: coupled with Na-K pump which reduces [K]interstitial plasma K leaves peritubular capillary the pump get K inside the tubular cells which has many K channels to help K to get out to the tubular lumin passively
-K channels in the proximal tubules are located at the basolateral side

-control of K secretion: increased [K]plasma stimulation of adrenal cortex increase aldosterone increase in K secretion & Na reabsorption

Lumen

Tubular cell

Interstitial fluid

Peritubular capillary

Diffusion

K+ channel Active transport

Diffusion

Fig. 13-14, p. 423

3- organic anions & cations: -two types of carriers one for anions & the other for cations: -prostaglandins -food additives -histamine & nor-epinephrine -environmental pollutants (pesticides), drugs

urine excretion

125mL/min is filtered, 124mL/min is reabsorbed, so 1mL/min is excreted If 125mL/min is filtered, and we have a slightly reduced reabsorption (123mL/min) then urine excretion is doubled (2mL/min) By excreting substances in the urine, kidneys clear the plasma flowing through them of these substances

Plasma clearance

Plasma clearance of any substance is the volume of plasma completely cleared of that substance by the kidneys per minute

-a substance (X) that is filtered but not reabsorbed or secreted has a plasma clearance= GFR 125mL/min of plasma is filtered containing an amount of X, this amount of X is left behind and is excreted with urine thus each minute 125mL of plasma will be cleared from X example inulin produced chemically

Peritubular capillary

Glomerulus

Tubule

In urine

For a substance filtered and not reabsorbed or secreted, such as inulin, all of the filtered plasma is cleared of the substance. Fig. 13-16a, p. 426

-a substance (Y) is filtered and reabsorbed but not secreted has a plasma clearance that is less than GFR examples: a- glucose pl. cl. = 0 b- urea pl. cl. =62.5mL/min

For a substance filtered, not secreted, and completely reabsorbed, such as glucose, none of the filtered plasma is cleared of the substance.

Fig. 13-16b, p. 426

For a substance filtered, not secreted, and partially reabsorbed, such as urea, only a portion of the filtered plasma is cleared of the substance.

Fig. 13-16c, p. 426

- a substance (Z) is filtered and secreted but not reabsorbed has a plasma clearance that is larger than GFR H+ is an example which is cleared by the following rates: 125mL/min by filtration & 25mL/min by secretion so it has a pl. cl =150mL/min paraaminohippuric acid (PAH), 20% of this chemical is filtered, and the remaining 80% will be secreted so it a has a pl. cl =plasma flow rate (625mL/min)

For a substance filtered and secreted but not reabsorbed, such as hydrogen ion, all of the filtered plasma is cleared of the substance, and the peritubular plasma from which the substance is secreted is also cleared.

Fig. 13-16d, p. 426

Urine excretion of varying concentrations

Interstitial fluid of the medulla build up a large osmotic gradient The concentration of fluid progressively increases from the cortex down through the depth of the medulla up to 1200mOsmole/L

Medulla

Cortex

All values in milliosmols (mosm)/liter.

Fig. 13-17, p. 427

Urine is excreted in the range of 100-1200 mOsmole/L depending on body fluid status: 1- ideally 1mL/min, isotonic 2- overhydration up to 25mL/min, hypotonic, 100mOsmole/L 3-dehydration 0.3mL/min hypertonic, up to 1200mOsm/L 1, 2, 3 represent the medullary countercurrent system

Countercurrent multiplication (c.c.m)

In the proximal tubules, 65% reabsorbed (water & salts) so solvent & solute are equally absorbed, so the tonicity will remain isotonic

In the loop of henle: 1-descending limb: -high water permeability -no sodium reabsorption 2-ascending limb: -actively reabsorbed NaCl -impermeable for water

Glomerulus Bowmans capsule Proximal tubule Distal tubule

Cortex Medulla

Long loop of Henle

Collecting tubule

Fig. 13-19a, p. 430

Mechanism of c.c.m

Initial scene: interstitial fluid is 300mOsm/L Step1: -NaCl actively pumped from ascending with the force of 200mOsm/L dif. -water will be reabsorbed from the descending to equilibrate with the outside until both have 400mOsm/L

Step 1
Fig. 13-19b, p. 431

Step2: -movement of luminal filtrate so from ascending 200mOsm/L fluid to the distal tubules, & 300mOsm/L fluid from proximal tubules gets in the descending limb & in between 400mOsm/L is moved around the tip

From proximal tubule

To distal tubule

Step 2
Fig. 13-19c, p. 431

Step3: -ascending limb pumps NaCl while water is reabsorbed from the descending limb until 200mOsm/L dif. Is established between the ascending, the interstitial fluid & the descending

Step 3
Fig. 13-19d, p. 430

Step4: -movement of filtrate will again disrupt the 200mOsm/L gradient at the horizontal level Step5: -active NaCl pump in the ascending limb with water diffusion in the descending one -the 200mOsm/L is reestablished

From proximal tubule

to distal tubule

Step4

Step5

Step6: -filtrate movement again will change the gradient so that it will lead to a progressive increment in the tonicity of the fluid in the descending limb & decrement in the ascending one

From proximal tubule

To distal tubule

Step 6 and on
Fig. 13-19g, p. 431

Vasopressin effects

180L/day is filtered, 65% is reabsorbed in the prox. tubules, 15% is reabsorbed in the L.H, & the remaining 20% is reabsorbed in the distal tubules ~36L/day This 36L filtrate is very hypotonic (100mOsm/L), whereas the interstitial fluid is isotonic in the cortex and up to 1200mOsm/L in the collecting ducts through the medulla

Vasopressin effects

Vasopressin will make the distal & collecting ducts permeable to water Vasopressin is produced in the hypothalamus, stored in the posterior pituitary gland, & stimulated by hypertonicity of the ECF

Vasopressin binds receptors in the distal & collecting tubules activates cAMP promotes insertion of aquaporins in the luminal membrane

Vasopressin effects

The previous process is reversible by decreasing vasopressin Maximum effect of vasopressin: -everyday 600 mOsm of waste is produced, this should be dissolved in water, the normal ability of the kidneys to concentrate a sln. is 1200mOsm/L, so these 600mOsm will be dissolved in 0.5L

Vasopressin effects
-these 0.5L of urine is the minimum volume of urine that is required to excrete daily waste (obligatory water loss)

-if there is no vasopressin, the distal & collecting tubules are impermeable to water, so 20% of filtrate cannot be reabsorbed completely, so 25mL/min will be excreted & the fluid will be hypotonic

From proximal tubule

Filtrate has concentration of 100 mosm/liter as it enters distal and collecting tubules

Distal tubule

Cortex Loop of Henle In the face of a water deficit Medulla

Collecting tubule

Concentration of urine may be up to 1,200 mosm/liter as it leaves collecting tubule

= passive diffusion of H2O
= active transport of NaCl = portions of tubule impermeable to H2O

= permeability to H2O increased by vasopressin

Fig. 13-20a, p. 433

From proximal tubule

Filtrate has concentration of 100 mosm/liter as it enters distal and collecting tubules

Distal tubule

Cortex Loop of Henle In the face of a water excess Medulla

Collecting tubule

Concentration of urine may be as low as 100 mosm/liter as it leaves collecting tubule

= passive diffusion of H2O
= active transport of NaCl = portions of tubule impermeable to H2O

= permeability to H2O increased by vasopressin

Fig. 13-20b, p. 433