Anatomy and Physiology, Seventh Edition

Rod R. Seeley Idaho State University Trent D. Stephens Idaho State University Philip Tate Phoenix College

Chapter 26 Lecture Outline*

*See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes.

1
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Kidney Functions
Filters blood plasma
returns useful substances to blood eliminates waste

Regulates
osmolarity of body fluids, blood volume, BP acid base balance

Secretes
renin and erythropoietin

Detoxifies free radicals and drugs Gluconeogenesis

Nitrogenous Wastes
Urea
proteinspamino acids pNH2 removed pforms ammonia, liver converts to urea

Uric acid
nucleic acid catabolism

Creatinine
creatine phosphate catabolism

Renal failure
azotemia: oBUN, nitrogenous wastes in blood uremia: toxic effects as wastes accumulate

Excretion
Separation of wastes from body fluids and eliminating them; by four systems
respiratory: CO2 integumentary: water, salts, lactic acid, urea digestive: water, salts, CO2, lipids, bile pigments, cholesterol urinary: many metabolic wastes, toxins, drugs, hormones, salts, H+ and water
4

The Nephron
Functional and histological unit of the kidney Parts of the nephron: Bowmans capsule, proximal tubule, loop of Henle (nephronic loop), distal tubule Urine continues from the nephron to collecting ducts, papillary ducts, minor calyses, major calyses, and the renal pelvis Collecting ducts, parts of the loops of Henle, and papillary ducts are in the renal medulla
5

Types of Nephrons
Juxtamedullary nephrons. Renal corpuscle near the cortical medullary border. Loops of Henle extend deep into the medulla. Cortical nephrons. Renal corpuscle nearer to the periphery of the cortex. Loops of Henle do not extend deep into the medulla. Renal corpuscle. Bowmans capsule plus a capillary bed called the glomerulus.

Renal Corpuscle
Bowmans capsule: outer parietal (simple squamous epithelium) and visceral (cells called podocytes) layers. Glomerulus: network of capillaries. Blood enters through afferent arteriole, exits through efferent arteriole.

Nephron Functions: Overview

Figure 19-2: Filtration, reabsorption, secretion, and excretion

Filtration
Movement of fluid, derived from blood flowing through the glomerulus, across filtration membrane Filtrate: water, small molecules, ions that can pass through membrane Pressure difference forces filtrate across filtration membrane Renal fraction: part of total cardiac output that passes through the kidneys. Varies from 12-30%; averages 21% Renal blood flow rate: 1176 mL/min = 21% x 5600 ml Renal plasma flow rate: renal blood flow rate X fraction of blood that is plasma: 650 mL/min = 1176 x 55% Filtration fraction: part of plasma that is filtered into lumen of Bowmans capsules; average 19% Glomerular filtration rate (GFR): amount of filtrate produced each minute. 125 ml/min = 180 L/day; 650 ml x 19% = 125ml/min Average urine production/day: 1-2 L. Most of filtrate must9be reabsorbed

Filtration
Filtration membrane: filtration barrier. It prevents blood cells and proteins from entering lumen of Bowmans capsule, but is many times more permeable than a typical capillary Fenestrated endothelium, basement membrane and pores formed by podocytes Filtration pressure: pressure gradient responsible for filtration; forces fluid from glomerular capillary across membrane into lumen of Bowmans capsules Forces that affect movement of fluid into or out of the lumen of Bowmans capsule Glomerular capillary pressure (GCP): blood pressure inside capillary tends to move fluid out of capillary into Bowmans capsule Capsule pressure (CP): pressure of filtrate already in the lumen Blood colloid osmotic pressure (BCOP): osmotic pressure caused by proteins in blood. Favors fluid movement into the capillary from the lumen. BCOP greater at end of glomerular capillary than at beginning because of fluid leaving capillary and entering lumen Filtration pressure (10 mm Hg) = GCP (50 mm Hg) CP (10 mm Hg) BCOP (30 mm Hg)
10

Filtration Pressure

11

Filtration
High glomerular capillary pressure results from
Low resistance to blood flow in afferent arterioles Low resistance to blood flow in glomerular capillaries High resistance to blood flow in efferent arterioles: small diameter vessels

Filtrate is forced across filtration membrane Changes in afferent and efferent arteriole diameter alter filtration pressure
Dilation of afferent arterioles/constriction efferent arterioles increases glomerular capillary pressure, increasing filtration pressure and thus glomerular filtration
12

Regulation of Glomerular Filtration

If the GFR is too high:
Urine output rises p Dehydration, electrolyte depletion

If the GFR is too low:

Everything is reabsorbed, including wastes that are normally disposed of

GFR is controlled by adjusting glomerular blood pressure through:

Autoregulation Sympathetic control Hormonal mechanisms: Renin and Angiotensin

13

Autoregulation and Sympathetic Stimulation

Autoregulation Renal autoregulation maintains a nearly constant glomerular filtration rate over a wide range of systemic blood pressure GFR constant as systemic BP changes between 90 and 180 mm Hg Involves changes in degree of constriction in afferent arterioles As systemic BP increases, afferent arterioles constrict and prevent increase in renal blood flow Increased rate of blood flow of filtrate past cells of macula densa: signal sent to juxtaglomerular apparatus, afferent arteriole constricts Sympathetic stimulation: norepinephrine Constricts small arteries and afferent arterioles Decreases renal blood flow and thus filtrate formation During shock or intense exercise: intense sympathetic stimulation, rate of filtrate formation drops to a few mm
14

Renal Autoregulation of GFR

o BP p constrict afferent arteriole, dilate efferent q BP p dilate afferent arteriole, constrict efferent Stable for BP range of 80 to 170 mmHg (systolic) Cannot compensate for extreme BP
15

Renal Autoregulation of GFR

Myogenic mechanism
o BP p stretches afferent arteriole p afferent arteriole constricts p restores GFR

Tubuloglomerular feedback
Macula densa on DCT monitors tubular fluid and signals juxtaglomerular cells (smooth muscle, surrounds afferent arteriole) to constrict afferent arteriole to q GFR
16

Negative Feedback Control of GFR

17

Sympathetic Control of GFR

Strenuous exercise or acute conditions (circulatory shock) stimulate afferent arterioles to constrict q GFR and urine production, redirecting blood flow to heart, brain and skeletal muscles

18

Renin-Angiotensin Aldosterone

19

Effects of Angiotensin II

20

Tubular Reabsorption: Overviewas filtrate flows Tubular reabsorption: occurs

Diffusion Facilitated diffusion Active transport Cotransport Osmosis

through the lumens of proximal tubule, loop of Henle, distal tubule, and collecting ducts Results because of

Substances transported to interstitial fluid and reabsorbed into peritubular capillaries; 99% of filtrate volume. These substances return to general circulation through venous system
21

Tubular Reabsorption and Secretion

22

Peritubular Capillaries
Blood has unusually high COP here, and BHP is only 8 mm Hg (or lower when constricted by angiotensin II); this favors reabsorption Water absorbed by osmosis and carries other solutes with it (solvent drag)

23

Proximal Convoluted Tubules (PCT)

Reabsorbs 65% of GF to peritubular capillaries Great length, prominent microvilli and abundant mitochondria for active transport Reabsorbs greater variety of chemicals than other parts of nephron
transcellular route - through epithelial cells of PCT paracellular route - between epithelial cells of PCT

Transport maximum: when transport proteins of cell membrane are saturated; blood glucose > 220 mg/dL some remains in urine
(glycosuria); glucose Tm = 320 mg/min

24

Mechanisms of Reabsorption in the Proximal Convoluted Tubule

25

Tubular Maximum

Maximum rate at which a substance can be actively absorbed Each substance has its own tubular maximum Normally, glucose concentration in the plasma (and thus filtrate) is lower than the tubular maximum and all of it is reabsorbed; none of it is found in the urine In diabetes mellitus tubular load exceeds tubular maximum and glucose appears in urine. Urine volume increases because glucose in filtrate increases osmolality of filtrate reducing the effectiveness of water reabsorption (osmotic diuresis). 26 Accounts for dehydration of diabetes.

Reabsorption in Loop of Henle

Loop of Henle descends into medulla; interstitial fluid is high in solutes. Water reabsorption is NOT coupled to solute reabsorption! Descending thin segment is highly permeable to water. Water moves out of nephron, reducing the volume of filtrate by another 15% and increasing its osmolarity (more concentrated). Ascending thin segment is not permeable to water, but is permeable to solutes. Solutes diffuse out of the tubule and into the more dilute interstitial fluid as the ascending limb projects toward the cortex. At the end of the loop of Henle, inside of nephron is 100 mOsm
27

Reabsorption in Distal Tubule and Collecting Duct

Active transport of Na+ out of tubule cells into interstitial fluid with cotransport of Cl Na+ moves from filtrate into tubule cells due to concentration gradient Collecting ducts extend from cortex (interstitial fluid 300 mOsm/kg) through medulla (interstitial fluid very high) Water moves by osmosis from distal tubule and collecting duct into more concentrated interstitial fluid Permeability of wall of distal tubule and collecting ducts have variable permeability to water Urine can vary in concentration from low volume of high concentration to high volume of low concentration
28

Tubular Secretion of PCT and Nephron Loop

Waste removal
urea, uric acid, bile salts, ammonia, catecholamines, many drugs

Acid-base balance
secretion of hydrogen and bicarbonate ions regulates pH of body fluids

Primary function of nephron loop

water conservation generates salinity gradient, allows CD to conc. urine also involved in electrolyte reabsorption

29

DCT and Collecting Duct

Principal cells receptors for hormones; involved in salt/water balance Intercalated cells involved in acid/base balance Function
fluid reabsorption here is variable, regulated by hormonal action
30

DCT and Collecting Duct

Aldosterone effects
q BP p renin release p angiotensin II formation angiotensin II stimulates adrenal cortex adrenal cortex secretes aldosterone
promotes Na+ reabsorption p promotes water reabsorption p q urine volume p maintains BP
31

DCT and Collecting Duct

Effect of ADH
dehydration stimulates hypothalamus hypothalamus stimulates posterior pituitary posterior pituitary releases ADH ADH o water reabsorption q urine volume

32

DCT and Collecting Duct

Atrial natriuretic peptide (ANP)
atria secrete ANP in response to o BP has four actions: 1. dilates afferent arteriole, constricts efferent arteriole - o GFR 2. inhibits renin/angiotensin/aldosterone pathway 3. inhibits secretion and action of ADH 4. inhibits NaCl reabsorption

Promotes Na+ and water excretion, o urine volume, q blood volume and BP
33

DCT and Collecting Duct

Effect of PTH
o calcium reabsorption in DCT - o blood Ca2+ o phosphate excretion in PCT, q new bone formation stimulates kidney production of calcitriol

34

Collecting Duct Concentrates Urine

Osmolarity 4x as concentrated deep in medulla Medullary portion of CD is more permeable to water than to NaCl

35

Control of Water Loss

Producing hypotonic urine
NaCl reabsorbed by cortical CD water remains in urine

Producing hypertonic urine

dehydration p o ADH p o aquaporin channels, o CDs water permeability more water is reabsorbed urine is more concentrated
36

Medullary Concentration Gradient

In order to concentrate urine (and prevent a large volume of water from being lost), the kidney must maintain a high concentration of solutes in the medulla Interstitial fluid concentration (mOsm/kg) is 300 in the cortical region and gradually increases to 1200 at the tip of the pyramids in the medulla Maintenance of this gradient depends upon
Functions of loops of Henle Vasa recta flowing countercurrent to filtrate in loops of Henle Distribution and recycling of urea
37

Osmotic Gradient in the Renal Medulla

38 Figure 25.13

Countercurrent Exchange System

Formed by vasa recta
provide blood supply to medulla do not remove NaCl from medulla

Descending capillaries
water diffuses out of blood NaCl diffuses into blood

Ascending capillaries
water diffuses into blood NaCl diffuses out of blood

39

Countercurrent Multiplier
Recaptures NaCl and returns it to renal medulla Descending limb
reabsorbs water but not salt concentrates tubular fluid

Ascending limb
reabsorbs Na+, K+, and Clmaintains high osmolarity of renal medulla impermeable to water tubular fluid becomes hypotonic

Recycling of urea: collecting duct-medulla

urea accounts for 40% of high osmolarity of medulla

40

Countercurrent Multiplier of Nephron Loop Diagram

41

Loops of Henle and vasa recta function together to maintain a high concentration of solutes in the interstitial fluids of the medulla and to carry away the water and solutes that enter the medulla from the loops of Henle and collecting ducts Water moves out of descending limb and enters vasa recta Solutes diffuse out of ascending thin segment and enter vasa recta, but water does not Solutes transported out of thick segment of ascending enter the vasa recta Excess water and solutes carried away from medulla without reducing high concentration of solutes Concentration of filtrate reduced to 100 mOsm/kg by the time it reaches distal tubule
42
Figure 20-10: Countercurrent exchange in the medulla of the kidney

Maintenance of Osmolarity in Renal Medulla

43

Summary of Tubular Reabsorption and Secretion

44

Formation of Concentrated Urine

Antidiuretic hormone (ADH) inhibits diuresis In the presence of ADH, 99% of the water in filtrate is reabsorbed ADH-dependent water reabsorption is called facultative water reabsorption ADH is the signal to produce concentrated urine
Stimulates the insertion of aquaporins into apical membranes of DCT and collecting ducts

The kidneys ability to respond depends upon the high medullary osmotic gradient

45

Formation of Dilute Urine

Filtrate is diluted in the ascending loop of Henle. Water permeability of collecting ducts is extremely low Dilute urine is created by allowing this filtrate to continue into the renal pelvis (water diuresis) Ocurrs as long as antidiuretic hormone (ADH) is not being secreted Collecting ducts remain impermeable to water; no further water reabsorption occurs Sodium and selected ions can be removed by active and passive mechanisms Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma) Diabetes insipidus-condition in which no ADH is secreted or kidney fails to respond to ADH; 20-25 L of urine excreted per day Osmotic diuresis- increased urine flow due to increase solute excretion; occurs in diabetes mellitus or inadequate Na+ reabsorption

46

Composition and Properties of Urine

Appearance
almost colorless to deep amber; yellow color due to urochrome, from breakdown of hemoglobin (RBCs)

Odor - as it stands bacteria degrade urea to ammonia Specific gravity

density of urine ranges from 1.001 -1.028

Osmolarity - (blood - 300 mOsm/L) ranges from

50 mOsm/L to 1,200 mOsm/L in dehydrated person

pH - range: 4.5 - 8.2, usually 6.0 Chemical composition: 95% water, 5% solutes
urea, NaCl, KCl, creatinine, uric acid
47

Urine Volume
Normal volume - 1 to 2 L/day Polyuria > 2L/day Oliguria < 500 mL/day Anuria - 0 to 100 mL/day

48

Diabetes
Chronic polyuria of metabolic origin With hyperglycemia and glycosuria
diabetes mellitus I and II, insulin
hyposecretion/insensitivity

gestational diabetes, 1 to 3% of pregnancies ADH hyposecretion diabetes insipidus; CD q water reabsorption

49

Diuretics
Effects
o urine output q blood volume

Uses
hypertension and congestive heart failure

Mechanisms of action
o GFR q tubular reabsorption
50

Voiding Urine - Micturition

200 ml urine in bladder, stretch receptors send signal to sacral spinal cord Signals ascend to
inhibitory synapses on sympathetic neurons micturition center (integrates info from amygdala, cortex) further inhibit sympathetic neurons stimulate parasympathetic neurons urinary bladder contraction relaxation of internal urethral sphincter
51

Signals descend to

Result

sacral spinal cord inhibit somatic neurons - relaxes

External urethral sphincter - corticospinal tracts to

Neural Control of Micturition

52