Renal Basic Good Notes

8/13/2019 Renal Basic Good Notes

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BIO 3520 Notes, 4/06/09

RENAL PHYSIOLOGY

I. Introduction. [Widmaier,pp. 486-487]

A. Urinary systemis involved in production, storage,and elimination of

urine.

B. Organization (fig.14-1).

1. Kidneys -- remove water and waste products toform urine.

2. Ureters -- drain urine from kidneys.

3. Bladder -- storage of urine.

4. Urethra -- elimination of urine.

II. Kidneys.[pp. 486-492]

A. Functions (table 14-1).

1. Control of body water balance.

a. Control of urine volume is most importantmechanism.
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b. What is second most important?

2. Control of electrolyte balance.

a. Na+, Cl-, Ca++, and others.

3. Excretion of metabolic waste products (ex. urea).

4. Elimination of foreign chemicals (ex. drugs,poisons).

B. Anatomy (fig.14-4).

1. Cortex.2. Medulla.3. Renal pelvisdrains into ureter.

C. Microscopic anatomy of the kidney.

1. Functional unit = nephron(fig.14-2a).a. One million nephrons in each kidney.b. Made up of a tuft of capillaries and a tubule.

2. Tuft of capillaries -- glomerulus.a. Function -- filtrationof plasma.

3. Plasma filtrateenters blind end of tubule -- Bowman's capsule.

4. Plasma filtrate travels through tubule and isconverted to urine.

a. Function of tubule -- selective secretionandreabsorptionof

substances.
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b. Structures.

1. Bowman's capsule.

2. Proximal tubule.

3. Loop of Henle.a. Descending limb -- dips into medulla.b. Ascending limb -- returns to cortex.

4. Distal tubule.

5. Collecting duct -- shared by manynephrons.

5. Final product (urine) drains into renal pelvis.

D. Renal circulation.

1. Blood enters via renal artery, which branches offaorta(figurea).

2. Renal veindrains into inferior vena cava.

3. Renal blood flow is more than 1 liter/min.

3. Renal arterybranches into smaller arteries(figurea), then

afferent arterioles(figurea).

4. Tufts of capillaries -- glomeruli.

5. Efferent arterioles.
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6. Peritubular capillariessurround tubules.

7. Venules and veins return blood to renal vein.

E. Overview of renal processes (fig.14-6).

1. Glomerular filtration.2. Tubular secretion.3. Tubular reabsorption.4. Urine concentrating mechanism.

aFox, S.I. Human Physiology,7th ed., McGraw-Hill, New York,

2002. Copyrightrestrictions apply.

III. GlomerularFiltration. [pp. 492-494]

A. Glomerular filtration is the starting point for theproduction of urine.

B. Glomerular filtration = Passage of protein-freeplasma from the

glomerular capillaries into Bowman's capsule.

C. Filtration apparatus (figs.14-3and 14-5).

1. Glomerular capillaries have single epithelial cell

layer.2. Bowman's capsule lined by a single epithelial cell

layer.3. Capillary walls and lining of capsule contain large

pores.
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D. Mechanism of filtration (figurea).

1. Glomerulus and capsule are freely permeable towater and most

molecules.a. Impermeable to cells or proteins.

2. Net movement of water and ions is out ofcapillaries into Bowman's

capsule.

a. Driving force is hydrostatic pressurein

glomerulus(i.e. capillary blood pressure).

b. Glomerular capillary BP = 50 mmHg.

c. Higher than in most capillaries due to largediameter of afferent

arterioles and resistance in efferent arterioles.

3. Analyze contents of capsule by micropuncture.

a. Filtrate has same composition as blood plasma,except it contains

no proteins.

D. Glomerular filtration rate (GFR) = Volume of fluidfiltered from plasma

per minute.1. Normal GFR = 120 ml/min = 180 L/day.

E. Determination of GFR -- clearance of creatinine.
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IV. RenalClearance. [pp. 497-498]

A. Renal clearance = Volume of plasma from which asubstance is

completely removed per minute.

B. Amount of substance removed fromplasma = amount excreted in urine.

Cl = UV

P

C. Example: Clearance of creatinine.

1. Creatinine is a breakdown product of creatine inmuscle.

2. Freely filtered.3. Neither reabsorbed nor secreted.

U = 60 mg/dlV = 2 ml/minP = 1 mg/dl

Clcreatinine =

D. Clearances of different substances will vary,depending on the degree

to which they are reabsorbed or secreted by thetubules.


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V. Tubular Secretion. [pp.496, 517, 520-521]

A. About 80% of renal blood flowing through the kidneyspasses through the

glomerulus without being filtered.

1. Blood that is not filtered enters the efferent arterioleand peritubular

capillaries.

2. Opportunity for exchange of substances betweenfiltrate (in tubules)

and plasma (in peritubular capillaries).

3. Function of the tubules is to separatesubstancesthat are to be

conservedin the body from those that are to beeliminatedin the urine.

B. Tubular secretion = Selective transfer ofsubstances from blood into

tubular fluid (figurea).

C. Purpose is to more rapidly eliminate certainsubstances from the body.

D. Clearance is greaterthan GFR.

E. Example 1: Para-aminohippuric acid (PAH).

1. Freely filtered, totally secreted (substance X in fig.14-7).
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2. Inject PAH > find almost none in renal vein.

3. ClPAH = 625 ml/min.

4. ClPAHis used to measure renal plasma flow.

5. GFR is about 20% of RPF -- i.e. about 20% ofblood flowing through

the kidneys is filtered.

F. Example 2: Penicillin.

1. Filtered at glomerulus.2. Secreted with high efficiency (figure).3. Results in rapid elimination of penicillin from the

body.

G. Example 3: Hydrogen ion (H+).

1. Secretion rate is variable.2. Important in control of acid-base balance.

H. Renal control of acid-base balance.

1. Important to maintain normal H+concentration inthe body fluids.

2. Normal pH of arterial blood is 7.4.

a. Increase [H+] > decreasepH > acidosis.

b. Decrease [H+] > increasepH > alkalosis.

3. Urine pH is about 6.
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4. H+concentration is regulated by kidneysand

lungs.

5. Feedback control of acid-base balance.

a. Controlled variable = H+concentrationinblood.

b. To correct an acidosis >

c. To correct an alkalosis >

VI. Tubular Reabsorption. [pp. 494-496, 501-502,506-507, 523]

A. Opposite of tubular secretion (figurea).
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B. Tubular reabsorption = Selective transfer ofsubstances from tubular

fluid into blood.

1. Substances that were originally filtered move backinto blood.

C. Purpose is to conserve substances that wouldotherwise be excreted

in the urine.

D. Substances that are to be conserved are reabsorbed,

while substancesthat are to be eliminated are often secreted.

1. Amount excreted = Amt filtered + amt secreted - amt reabsorbed

E. Clearance is less than the GFR.

F. Example 1: Sodium.

1. 99% reabsorbed (substance Y in fig.14-7).

2. ClNa = 1 ml/min.

3. Mechanism -- primary active transport.a. Responsible for 80% of kidney's total energy

requirement.

4. Amount of reabsorption varies in different parts ofthe tubule.

Segment
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Proximal tubule

Descending limb

Ascending limb

Distal tubule

Total Reabsorption

5. Rate of Na+reabsorption is regulated in order tomaintain plasma

Na+levels.

6. As Na+is reabsorbed, so is water.

7. Diuretics(ex. furosemide, Lasix) increase urinevolume.

a. Block tubular reabsorption of Na+.b. Useful in treatment of hypertension.

G. Example 2: Glucose.

1. 100% reabsorbed (substance Z in fig.14-7).

2. Normally, no glucose in urine.

a. Clglucose =

3. Site -- proximal tubule.

4. Mechanism -- secondary active transport

(cotransport with Na

+

).

5. Exhibits saturation.

a. When blood glucose concentration isabnormally high (ex. diabetes
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mellitus), rate of filtration exceeds maximumrate of reabsorption

(fig.14-11).

b. Transport maximum (Tm) = Maximal rate ofreabsorption of a

substance by the renal tubular cells.

c. Excess glucose "spills over" into urine(glucosuria).

H. Example 3: Urea.

1. 50% reabsorbed.

2. Mechanism -- simple diffusion.

3. Lower rate of reabsorption allows for significantexcretion of urea.

I. Summary of three renal processes (figurea).

J. Summary of range of clearances.
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VII. Regulation of SodiumExcretion. [pp. 506-509]

A. The renin-angiotensin-aldosterone systemis acomplex mechanism

for regulation of plasma sodium levels.

B. Aldosterone.

1. Hormone secreted by adrenal cortex (figureb).2. Stimulates Na+reabsorption from distal tubules.

3. Aldosterone secretion is stimulated by angiotensinII.

C. Renin-angiotensin system.

1. Juxtaglomerular apparatus(fig.14-5).

a. Region of nephron where afferent arteriole anddistal tubule come

into contact.

b. Juxtaglomerular cells in afferent arteriolesecrete the enzyme,

renin, into blood.

2. Stimuli to renin secretion.

a. Decreased renal arteriolar pressure.1. JG cells act as stretch receptors.

b. Decreased distal tubular sodium.1. Detected by macula densacells in distal

tubule.
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c. Stimulation of renal sympathetic nerves.

3. Renin causes cleavage of circulating protein,

angiotensinogen, toproduce angiotensin I.a. Angiotensinogen and angiotensin I are both

inactive.

4. Angiotensin I is cleaved by angiotensinconverting enzymein lung

capillaries to produce angiotensin II.

5. Angiotensin II is a potent stimulator of aldosteronesecretion

(fig.14-21,figure).

D. Feedback control of sodium excretion.

1. Controlled variables.

a. Renal arteriolar pressure(reflects MAP).

b. Distal tubular Na+concentration (reflectsplasma Na+conc).

2. Example: Na+deficiency(fig.14-22).
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b Sherwood, L. Human Physiology: From Cells to Systems,5th ed.,Brooks/Cole,

Belmont, CA, 2004. Copyright restrictions apply.

VIII. Urine Concentrating Mechanism. [pp. 501-503, 510-511]

A. Introduction.

1. Water intake must equal water output in order tomaintain body water

balance.

2. When water is scarce, an animal must be able toconcentrate the urine

and thus limit water loss.

3. Minimum volume of urine that must be produced is0.3 ml/min.

B. Function of the collecting duct is to concentrate theurine by reabsorbing

water.

C. Fluid leaving distal tubule has the composition of very


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dilute urine.

1. Mechanism responsible for dilute tubular fluid in thedistal tubule

(fig.14-17,figurea).

a. Ascending limbof loop of Henle is permeableto Na+and Cl-,

but impermeable to water.

b. As filtrate ascends, Na+and Cl-are activelyreabsorbed, but H2O

does not follow.

c. By the time the filtrate reaches the distal tubule,it is very dilute

(100 mosmol/L).

2. Gradient is established in interstitial fluid of kidney.

a. Descending limb is permeable to water, but notto Na+and Cl-.

b. Counter-current exchange mechanismconcentrates the interstitial

fluid in the medulla(1400 mosmol/L near renalpelvis).

c. Osmolarity in cortex is similar to plasma (300

mosmol/L).

D. Reabsorption of water from collecting duct dependson antidiuretic

hormone (ADH, vasopressin)secreted by posteriorpituitary.
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1. ADH causes insertion of aquaporinsinto

membrane of collecting ductcells (figure).

2. In presenceof ADH, collecting duct is permeableto water >

water is reabsorbed > urine is concentrated.

3. In absenceof ADH, collecting duct is notpermeableto water >

water is not reabsorbed > urine is dilute.

4. Urine volume is low in presence of ADH and high inabsence of ADH.

5. Alcohol blocks ADH secretion.

E. Renal control of body water balance.

1. Controlled variable = plasma osmolarity.

2. Sensor = osmoreceptorsin hypothalamus.

3. Control center = hypothalamus.

4. Example: Dehydration(increased plasmaosmolarity).
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I. Comparison of urine concentrating abilities of variousmammals.

1. Corresponds to availability of water in theenvironment (figure).

2. No differences in posterior pituitary or ability tosecrete ADH.

3. Differences are in the lengths of the loops of Henle.

a. Beaver -- all short loops.b. Human -- combination of short loops and long

loops.c. Kangaroo rat (figure) -- all long loops.

IX. Urination. [pp.487, 498-499]
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A. Urine passes from collecting ducts into renal pelvis,

then ureters(fig.14-1).

1. No further changes in urine composition.

B. Ureters, urinary bladder, and urethraare all linedwith smooth muscle.

1. Wave of smooth muscle contraction moves urine tobladder in a few sec.

C. Walls of bladder can be stretched as it fills.

1. Holds about 500 ml when full.

D. Two sphincters at opening to urethra (fig. 14-13).

1. Internal urethral sphincter -- smooth muscle.

2. External urethral sphincter -- skeletal muscle.

E. Urine is usually sterile.

F. Micturition reflexis an example of a spinal reflex(figureb).

1. Bladder wall contains stretch receptors.

2. When stretched, impulses are sent to lower spinalcord.

3. Activates parasympathetic neuronsgoing tobladder and urethra.

4. Bladder wall contractsinvoluntarily and internalurethral sphincter
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relaxes > urge to urinate.

5. Urination can be prevented by voluntarilycontracting the external

urethral sphincter.

6. Relaxexternal urethral sphincter > contents ofbladder are released

out urethra > urination.

G. Urinary incontinence = Inability to control urination.

1. Infants.2. Spinal cord injury.3. Some elderly people.

X. KidneyDisorders. [pp. 523-525]

A. Kidney stones(figure).

1. Formation of calcium crystals in renal pelvis.2. Painful passage through ureters (figure).

B. Renal failure.

1. Damage to kidneys so that glomeruli fail to filter

blood.

2. Causes.

a. Infection of the kidneys (nephritis).b. Inadequate blood flow to kidneys.
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c. Complete obstruction of urinary tract.

3. Consequences.

a. Decreased GFR.b. Leakage of proteins into tubular

filtrate > proteinuria.c. Buildup of toxic substances in

blood > uremia.

4. May be temporary or permanent.

5. Treatment.

a. Dialysis(artificial kidney) (fig.14-34).

1. Needles in one artery and one vein.

2. Blood flows through dialyzer.

3. Contains dialyzing solution -- sameconcentration of ions and

small molecules as normal plasma.

4. Semipermeable membraneseparatesdialyzing solution from

blood flowing through dialyzer.

5. Permeable to ions and small molecules, but

not blood cells and proteins.

6. Large surface area provides maximumexchange of molecules.

7. Waste products move into dialyzing
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fluid > discarded.

8. Must be dialyzed every few days.

b. Kidney transplant(figure).

1. Most common type of organ transplant.2. Only one kidney is transplanted.3. Donor may be an accident victim or a close

relative.

XI. Urinalysis. [pp. 496, 523]

A. Urine is a body fluid that is easily and painlesslyobtained.

B. The measurement of chemical substances in urine(urinalysis) can be

important in the diagnosis of a variety of diseases.

1. Diseases of the kidney and urinary tract.2. Metabolic diseases (ex. diabetes).3. Diseases of other organs (ex. liver).4. Presence of drugs and their metabolites.

C. Urinalysis using reagent strips (figure).

1. Blood.

a. Red blood cells are too large to be filtered.

b. Positive test indicates hemoglobin in the urine(hematuria).
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c. Positive test is produced by:

1. Damage to glomerular capillaries.

2. Bleeding elsewhere in the urinary system.3. Strenuous exercise.4. Contamination from menstrual bleeding.

2. Ketones.

a. Ketone bodies are intermediates of fatty acidmetabolism.

b. Present in blood, but not usually found in urine.

c. Levels will be elevated when there is a highrate of fat metabolism.

1. Starvation.

a. Body depends heavily on fat metabolismas a primary energy

source.b. Excess ketones in blood appear in the

urine (ketonuria).

2. Diabetes mellitus.

3. Glucose.

a. Glucose is normally 100% reabsorbed.

b. Diabetes mellitus.

1. Inadequate amounts of insulin are secreted


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by the pancreas.2. Elevated blood glucose level

(hyperglycemia).3. Blood glucose level exceeds the

reabsorptive capacity of renaltubules (Tm) > glucose will appear in the

urine (glucosuria)(fig.14-11).

4. Protein.

a. Proteins are very large molecules that are not

normally filtered bythe glomeruli.

b. Protein in the urine (proteinuria) indicates thatthe permeability of

glomerular capillaries is abnormally high.

c. Causes:1. Renal failure.2. Infection of the kidneys (nephritis).3. Urinary tract infections.

d. About 5% of the normal population show slightproteinuria due to the

presence of small protein fragments.

5. Urine pH.

a. Urine is typically more acidicthan blood.

b. Tubular secretion of H+is a mechanism bywhich the acidity of

blood is regulated.
http://ux1.eiu.edu/~klmcgilliard/fig/wid11/1411.jpghttp://ux1.eiu.edu/~klmcgilliard/fig/wid11/1411.jpghttp://ux1.eiu.edu/~klmcgilliard/fig/wid11/1411.jpghttp://ux1.eiu.edu/~klmcgilliard/fig/wid11/1411.jpg


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c. pH of urine is highly variable (normal

range = 4.5 - 8.0).

D. Regulation of body water balance.

1. Water intake must equal water output in order tomaintain body water

balance.

2. Body water balance is maintained through theproduction of a

concentrated or dilute urine.

3. The solute concentration of a urine sample isestimated using a

urinometer.

a. Specific gravityis a measure of the density ofa solution

compared to water.

b. Specific gravity is proportional to soluteconcentration.

c. Normal urine specific gravity is between 1.010and 1.025.
http://ux1.eiu.edu/~klmcgilliard/fig/suppl/urinometer.jpghttp://ux1.eiu.edu/~klmcgilliard/fig/suppl/urinometer.jpghttp://ux1.eiu.edu/~klmcgilliard/fig/suppl/urinometer.jpg

Renal Basic Good Notes

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