Chapter 17 Physiology of the Kidneys

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Kidney Function
Is to regulate plasma and interstitial fluid composition by formation of urine More specifically, kidneys regulate:
Volume of blood plasma, which contributes to BP Waste products in blood Concentration of electrolytes in blood
Including Na+, K+, HCO3- , and others

Plasma pH (H+)

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Structure of Urinary System

Paired kidneys are on both sides of vertebral column below diaphragm
About size of fist

Urine flows from kidneys into ureters which transport it to urinary bladder

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Structure of Kidney
Cortex contains many capillaries and outer parts of nephrons Medulla consists of renal pyramids separated by renal columns Pyramids empty urine into minor calyces which unite to form a major calyx

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Structure of Kidney
Pyramids empty urine into minor calyces which unite to form a major calyx

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Structure of Kidneys continued

Major calyces join to form renal pelvis which collects urine Conducts urine to ureters which empty into bladder Bladder has a smooth muscle wall called the detrussor muscle

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Micturition Reflex (Urination) continued

Actions of internal and external urethral sphincters are regulated by reflex center located in sacral part of spinal cord Filling of bladder activates stretch receptors that send impulses to micturition reflex center
This activates Parasympathetic neurons causing slight contraction of detrusor muscle that pushes open the internal urethral sphincter creating sense of urgency There is voluntary control over external urethral sphincter (relaxes) Urination is then consciously initiated
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The Nephron
Is the structural/functional unit of kidney; responsible for forming urine
>1.25 million nephrons/kidney

Is a long tube and has associated blood vessels

Nephron Tubules and Blood Vessels

Glomerular (Bowman's) Capsule

Surrounds glomerulus Is where glomerular filtration occurs
Capsule collects and directs filtrate into Proximal Convoluted Tubule
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Glomerular Filtration
Glomerular capillaries and Bowman's capsule form a filter for blood
Glomerular capillaries are fenestrated (ie: have large pores between their endothelial cells)
Big enough to allow any plasma molecule to pass 100-400 times more permeable than other capillaries

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Glomerular Filtration continued

To enter tubule filtrate must pass through narrow slit diaphragms formed between pedicels (foot processes) of podocytes of glomerular capsule
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Glomerular Filtration continued

Plasma proteins are mostly excluded from the filtrate because of their large size and negative charge
The slit diaphragms are lined with a basement membrane composed of negative charges which repel negatively-charged proteins Some protein (especially albumin) normally enters the filtrate but most is reabsorbed by receptormediated endocytosis
In some diseases, a lot of protein appears in the urine (=proteinuria)- glomerulonephritis
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Glomerular Ultrafiltrate
Is the fluid that enters glomerular capsule, whose filtration was driven by blood pressure
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Glomerular Filtration Rate (GFR)

Is volume of ultrafiltrate produced by both kidneys/min
Averages 115 ml/min in women; 125 ml/min in men Totals about 180L/day (45 gallons)
So most filtered water must be reabsorbed or death would ensue from water lost through urination

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Measurement of Renal Blood Flow

Not all blood delivered to glomerulus is filtered into glomerular capsule
20% is filtered; rest passes into efferent arteriole and back into circulation Substances that aren't filtered can still be cleared by active transport (tubular secretion) into tubules further down nephron tubules

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Regulation of GFR
GFR is controlled by extrinsic and intrinsic (autoregulation) mechanisms Vasoconstriction or dilation of afferent arterioles affects rate of blood flow into glomeruli and thus GFR
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Sympathetic Effects
Sympathetic activity during exercise constricts afferent arterioles
Extrinsic regulation of GFR Significantly slows GFR Helps maintain blood volume and pressure and shunts blood to heart and muscles

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Renal Autoregulation (Intrinsic)

Allows kidney to maintain a constant GFR over a wide range of fluctuating BPs Achieved via effects of locally produced chemicals on afferent arterioles When mean arterial pressure (MAP) drops to 70 mm Hg, afferent arterioles dilate When mean arterial pressure (MAP) increases, afferent arterioles constrict

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The Three Processes of Urine Formation

Urine is formed by three Processes:

- Glomerular Filtration: movement of materials from glomerulus into nephron - Tubular Reabsorption: movement of nutrients from renal tubules back into blood
- Tubular Secretion: movement of wastes/excess materials from blood into renal tubules

Reabsorption of
Salt and H2O
The PCT returns most molecules and H2O from filtrate back into peritubular capillaries by tubular reabsorption:
About 180 L/day of ultrafiltrate produced; only 12 L of urine excreted/24 hours
Urine volume varies according to needs of body Minimum of 400 ml/day = urine necessary to excrete metabolic wastes (obligatory water loss)

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Proximal Convoluted Tubule

Ultrafiltrate in PCT is isosmotic to blood (300 mOsm/L) Thus reabsorption of H2O by osmosis cannot occur without active transport (AT) Is achieved by AT of Na+ out of filtrate Loss of + charges causes Cl- to passively follow Na+ Water then follows salt by osmosis
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Significance of PCT Reabsorption

~65% Na+, Cl-, and H2O is reabsorbed in PCT and returned to bloodstream An additional 20% is reabsorbed in descending loop of Henle Thus 85% of filtered H2O and salt are reabsorbed early in nephron
This is at a constant rate and independent of body hydration levels The remaining 15% is reabsorbed variably, depending on level of body hydration
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Concentration Gradient in Kidney

In order for H2O to be reabsorbed, interstitial fluid of kidney must be hypertonic to ultrafiltrate Osmolality of medullary interstitial fluid (12001400 mOsm) is 4X that of renal cortex and plasma (300 mOsm)
This concentration gradient results largely from loop of Henle which allows interaction between descending and ascending limbs

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Descending Limb Loop of Henle

Is permeable to H2O Is impermeable to, and does not actively transport, salt Because deep regions of medulla are hypertonic, H2O diffuses out of filtrate into interstitial fluid This reabsorbed H2O is then collected by capillaries
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Ascending Limb Loop of Henle

Is impermeable to H2O but permeable to salt; thick part provides active transport of salt out of filtrate AT of salt causes interstitial fluid to become hypertonic to ultrafiltrate
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Countercurrent Multiplier System

Countercurrent flow and proximity allow descending and ascending limbs of LH to interact in way that causes osmolality to build in medulla

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Countercurrent Multiplier System

Salt pumping in thick ascending limb raises osmolality around descending limb, causing more H2O to diffuse out of filtrate This raises osmolality of filtrate in descending limb which causes more concentrated filtrate to be delivered to ascending limb As this concentrated filtrate is subjected to AT of salts, it causes even higher osmolality around descending limb (positive feedback)
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Vasa Recta
Permeable to salt, H2O (via aquaporins) Recirculates salt, trapping some in medullary interstitial fluid Reabsorbs H2O coming out of descending limb Traps solutes but allows water to be reabsorbed back into systemic circulation

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Effects of Urea
Urea contributes to high osmolality in medullary region
Deep region of collecting duct is permeable to urea and it is reabsorbed Ascending limb absorbs urea Thus urea is trapped in medullary area
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Collecting Duct (CD)

Plays important role in water conservation Is impermeable to salt Permeability to H2O depends on levels of ADH

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Antidiuretic Hormone
Is secreted by posterior pituitary in response to dehydration Stimulates opening of aquaporins (water channels) of collecting duct (CD) When ADH is high, H2O is drawn out of CD by high osmolality of medullary interstitial fluid
And then reabsorbed by vasa recta
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Renal Clearance
Refers to ability of kidney to remove substances from blood and excrete them in urine Occurs by filtration and by secretion Secretion is opposite of reabsorption--substances from vasa recta are transported into tubule and excreted Reabsorption decreases renal clearance; secretion increases clearance

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Renal Clearance
Excretion rate = (filtration rate + secretion rate) - reabsorption rate

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Renal Clearance of Inulin

Since it is not reabsorbed nor secreted, the amount of inulin in the urine is an exact indication of GFR
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Renal Clearance of a Molecule Also Secreted

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Glucose and Amino Acid Reabsorption

Filtered glucose and amino acids are normally completely reabsorbed from ultrafiltrate
Occurs in PCT by cotransport with Na+
Transporter displays saturation if ligand concentration in ultrafiltrate is too high
Level that saturates carriers and achieves maximum transport rate is transport maximum (Tm)

Glucose and amino acid transporters arent saturated under normal conditions

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Glycosuria
Is presence of glucose in urine Occurs when glucose > 180-200mg/100ml plasma (= renal plasma threshold)
Glucose is normally absent from urine because plasma levels stay below this level Hyperglycemia has to exceed renal plasma threshold to cause glycosuria Diabetes mellitus occurs when chronic hyperglycemia results in glycosuria
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Renal Control of Electrolyte Balance

Kidneys regulate levels of Na+, K+, H+, HCO3-, Cl-, and PO4-3 by matching excretion to ingestion Control of plasma Na+ is important in regulation of blood volume and pressure Control of plasma of K+ is important in proper function of cardiac and skeletal muscles

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Control of Electrolyte Balance

Role of Aldosterone in Na+/K+ Balance

85% filtered Na+ and K+ reabsorbed before DCT

Remaining (15%) is variably reabsorbed in DCT and CD according to bodily needs
Regulated by aldosterone (controls K+ secretion/excretion and Na+ reabsorption/retention) In the absence of aldosterone secretion, some of the remaining 15% of Na+ is reabsorbed in DCT and CD When aldosterone is high in circulation ALL remaining Na+ is reabsorbed (thus none in the urine)
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 Is the only way K+ is excreted in urine Is directed by aldosterone and occurs in DCT and CD
High blood K+ or low blood Na+ will increase circulatory aldosterone and thus K+ secretion In absence of aldosterone, all K+ is reabsorbed and none excreted

K+ Secretion

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Control of Electrolyte Balance

The Juxtaglomerular Apparatus (JGA)
A specialized region in each nephron where afferent arteriole comes in contact with ascending limb and distal convoluted tubule

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Control of Electrolyte Balance Renin-Angiotensin-Aldosterone System (RAAS)

Begins with release of renin from granular cells of afferent arteriole due to low blood volume (thus pressure) and low flow in afferent arteriole:
Renin converts plasma angiotensinogen to angiotensin I
Which is then converted to Angio II by angiotensin-converting enzyme (ACE) in lungs Angio II stimulates release of aldosterone from adrenal cortex Aldosterone stimulates Na+ reabsorption Chloride and water follows and blood pressure is increased

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Control of Electrolyte Balance

Is region of ascending limb in contact with afferent arteriole Work opposite of RAAS Cells respond to levels of Na+ in ultrafiltrate

Macula Densa Cells

Inhibit renin secretion when Na+ levels are high Causing less aldosterone secretion, thus more Na+ excretion Lowers BP

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Control of Electrolyte Balance

Atrial Natriuretic Peptide (ANP) Is produced by atria due to stretching of walls Acts opposite to aldosterone Stimulates salt and H2O excretion Acts as a diuretic and a natriuretic

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Control of Electrolyte Balance

Na+, K+, and H+ Relationship
Na+ reabsorption in DCT and CD creates electrical gradient for H+ or K+ secretion
Hyperkalemia can cause acidosis because K+ is secreted at expense of H+

Comparatively, in severe acidosis, H+ is secreted at expense of K+ results in hyperkalemia

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Renal Acid-Base Regulation

Kidneys help regulate blood pH by excreting H+ and/or reabsorbing HCO3 Most H+ secretion occurs across walls of PCT in exchange for Na+ reabsorption (Na+/H+ antiporter) Normal urine is slightly acidic (pH = 5-7) because kidneys reabsorb almost all HCO3- and excrete excess H+

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Diuretics
Are used to lower blood volume because of hypertension, congestive heart failure, or edema Increase volume of urine by increasing proportion of glomerular filtrate that is excreted

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Diuretics
Loop diuretics are most powerful; inhibit ActiveTransport of salt in thick ascending limb of LH Thiazide diuretics inhibit NaCl reabsorption in 1st part of DCT Carbonic anhydrase inhibitors prevent H2O reabsorption in PCT when HCOs- is reabsorbed Osmotic diuretics increase osmotic pressure of filtrate

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Sites of Action of Clinical Diuretics

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