Objectives 1

Question 1

What is body fluid homeostasis?

Answer 1

A constant volume and composition of the body fluid compartments.

Question 2

What are the roles of the kidneys in the maintenance of body fluid homeostasis?

Answer 2

o Excretion of endogenous and exogenous waste products
o Regulation of water and electrolyte balance
o Regulation of body fluid pH
o Regulation of arterial blood pressure
o Regulation of RBC production
o Regulation of vitamin-D activity
o Gluconeogenesis

Question 3

What are the implications of severely impaired renal function for body fluid homeostasis?

Answer 3

.Metabolic acidosis with pH of 4.0mEq/L
.Uremic toxicity resulting in azotemia (An increase in plasma creatinine and BUN blood
urea nitrogen)
.Na+ and H2O imbalance resulting in a change in body fluid volume causing a change in
blood pressure
.Ca2+ and PO42- imbalance resulting in lack of vitamin D activation (low 1,25-OH2 vitamin
D) that decreases calcium absorption resulting in osteoporosis and bone fractures o Plasma protein imbalance resulting in osmotic imbalance and accumulation of fluid in the
interstitial space causing edema.
.Anemia caused by decreased erythropoietin synthesis by impaired kidneys. Low
erythropoietin results in a reduction of RBC production. o Depressed immune system

Question 4

What is renal function reserve capacity?

Answer 4

The ability of the kidney to maintain an adequate glomerular filtration rate GFR despite loss of function to one or both kidneys.

Question 5

What are the primary causes of acute and chronic renal failure?

Answer 5

o Acute renal failure ARF is typically reversible. Characterized by
 Pre-renal ARF-decrease in renal blood flow reduces glomerular filtration
 Intra-renal ARF- acute tubular necrosis (ATN) from ischemia or toxin reduces glomerular filtration
 Post-renal ARF- urinary tract obstruction increases pressure in kidney reducing glomerular filtration
o Chronic renal failure CRF irreversible, usually a progressive renal injury
 Diabetes 34%
 Hypertension 29%
 Glomerulonephritis 14%

Question 6

What are the treatment options for end-stage renal disease?

Answer 6

o Transplant

o Dialysis

Question 7

How does hemodialysis differ from peritoneal dialysis?

Answer 7

o Hemodialysis utilizes a membrane within an apparatus where blood and dialysis fluid can participate in osmotic exchange of solutes and water to remove waste products and excess water from the blood.
o Peritoneal dialysis utilizes dialysis fluid within the patients peritoneal cavity to remove wastes and excess water through osmotic exchange

Question 8

What are the limitations of dialysis?

Answer 8

o Hemodialysis
 takes 3-4 hours
 typically performed three times per week
 requires patient to be in proximity of a clinic with hemodialysis equipment
 patient must take blood thinner prior to hemodialysis
o Peritoneal dialysis
 completed 4-6 times per day
 higher risk of infection than hemodialysis
o Limitations of both types
 Body fluid homeostasis cannot be maintained
 Body weight increases between sessions
 Plasma creatinine increases between session

Question 9

What factors can affect the percentage of total body water (TBW)?

Answer 9

o Gender- men have more body water due to more muscle mass and less adipose
o Age- infants are 75% water, adults are 50-60% water, body water decreases with age

Question 10

What is percentage of total body water contained within each of the principal body fluid compartments?

Answer 10

o Intracellular 66.7% or 2/3
o Extracellular 33.3% or 1/3
 Interstitial fluid comprises 75% of the extracellular fluid
 Plasma comprises 25% of the extracellular fluid
 Trans-cellular fluid is comprised of CSF, aqueous humor, GI secretions, and urine

Question 11

What separates one compartment from another?

Answer 11

Selectively permeable membrane?

Question 12

How does the solute composition of the intracellular and extracellular fluid compartments differ?

Answer 12

o Intracellular fluid is high in potassium (K+), organic phosphates, and proteins
o Extracellular fluid is high in sodium (Na+), chloride (Cl-), and bicarbonate (HCO3-)

Question 13

What are some of the factors responsible for this unique distribution of solutes?

Answer 13

o Sodium and potassium differential is maintained by the sodium/potassium pump in the cellular membrane utilizing Na+-K+ATPase
o All membrane transporters that move solutes between the intra and extracellular compartments

Question 14

Why is extracellular fluid volume directly related to total body sodium (chloride)?

Answer 14

o Na+ and associated anions (Cl- and HCO3-) account for about 90% of the osmotic activity of extracellular fluid
o Changes in Na+ concentration in the intra or extra cellular compartments results in a change in water distribution. The movement of Na+ causes a hyper tonicity that is corrected by the movement of water and results in a return of the isotonic environment.
o changes in Na+ and associated ion content of the body cause changes in extracellular volume by the osmoreceptor-ADH and the Renin-Angiotensin-Aldosterone/ANP mechanisms

Question 15

What is the dilution principle and how can it be applied to the measurement of body fluid volumes?

Answer 15

o Compartment volumes are measured by determining the volume of distribution of a tracer substance.
o A known amount of a tracer is added to a compartment.
o The tracer concentration in that compartment is measured after allowing sufficient time for uniform distribution throughout the compartment.
o The compartment volume is calculated as:  Compartment Volume = (Amount of X Given) – (Amount of X Lost)/Concentration of X at Equilibrium

Question 16

Recognize markers that can be used to measure specific compartment volumes.

Answer 16

Extracellular volume markers
  Radiolabeled sodium
  Sucrose
  Mannitol
  Inulin
Plasma volume markers
  Iodinated albumin
  T-1824 (Evans blue)
Total body water
  Tritiated water
  Heavy water
  Antipyrine

Question 17

Understand how to calculate interstitial and intracellular fluid volume

Answer 17

o Interstitial volume = extracellular fluid volume – plasma volume
o Intracellular volume = total body water – extracellular fluid volume

Question 18

Why it is not possible to measure these volumes directly?

Answer 18

o Plasma volume must always be included in the measurement because it is the only fluid that can be sampled directly from the body once the marker has reached equilibrium. There is no clinical method for taking a direct interstitial or intracellular fluid sample from a living patient.

Question 19

When multiple measurements of a specific compartment volume are required, why is it important to use a single marker?

Answer 19

o Markers that are used in the same space may give slightly varying values based on composition differences of the marker.
o If a different marker is used for each measurement a clinically significant difference may be observed in the values that is due to a difference in marker composition not changes in the patients fluid volume

Question 20

Understand the concepts of osmosis and osmotic pressure, tonicity.

Answer 20

 Osmosis is the movement of water molecules through a selectively permeable membrane into a region of higher solute concentration
 Osmotic pressure is the driving force for movement of H2O across cellular membranes
 Tonicity
o Isotonic- inter and extracellular solute concentrations are equal no change in cell volume
o Hypotonic- intercellular solute concentration is higher than extracellular solute concentration, osmotic gradient into cell, cell swells
o Hypertonic- extracellular solute concentration is higher than intracellular solute concentration, cell shrinks

Question 21

Why is 300 mmol/L isotonic but 300 mmol/L urea hypotonic?

Answer 21

Urea is can diffuse across the plasma membrane, unlike Sodium Chloride or Sucrose (these DO NOT cross the plasma membrane)

Question 22

What are the principal factors involved in fluid exchange between interstitium and intracellular fluid?

Answer 22

o Plasma and interstitium; Starling Forces (hydrostatic pressure)
 At the arteriole
 Capillary hydrostatic pressure versus the interstitial oncotic pressure
 At the veinule
 Interstitial hydrostatic pressure versus the capillary oncotic pressure
 Calculated by JV = K= K F [(P [(PC – PI) – (π C – πI)]
o JV = fluid flux across capillary wall (vol/time)
o KF = the filtration coefficient
o PC = capillary hydrostatic pressure
o PI = interstitial hydrostatic pressure
o πC = capillary oncotic pressure
o πI = interstitial oncotic pressure
o Interstitium and intracellular fluid?
 Exchange of fluid between interstitium and intracellular fluid is determined by osmotic pressure. Equilibrium can be disrupted be various insults including
 Ingestion of water
 Intravenous infusions
 Dehydration

Question 23

Be able to interpret graphic representations of the effects of various manipulations on body fluid volumes and osmolality.

Answer 23

see graph in objectives

Question 24

Be able to calculate the effects of such manipulations on compartment volume and osmolality.

Answer 24

Calculate molarity molarity = moles of solute liters of solution
 Calculate equivalence stoichiometry of interaction between cations and anions determined by valence of the ions mEq concentration on an ion= total mM concentration X charge
 Calculate osmolality

Question 25

Would these calculations be valid if membrane permeable solutes were added?

Answer 25

No because these calculations are based on the movement of water across the membrane not solutes.

Question 26

What are the major anatomical subdivisions of the kidney (renal zones)?

Answer 26

o Outer cortex

o Inner medulla

Question 27

What is the relationship between this renal tissue and the renal calyces and pelvis?

Answer 27

o Cortex and medulla contain nephrons that filter plasma
o Nephron distal proximal tubules transfer filtrate to medullary collecting ducts that converge at the inner edge of the medulla forming the calyces
o The calyces transfer filtrate into the renal pelvis which connects to the ureter

Question 28

What are the names of the principal segments of the nephron, and their respective locations with the renal zones?

Answer 28

o Principal segments of nephron
 Proximal tubule>loop of Henle> distal tubule> collecting tubule
o Cortical (short looped) nephron
 Cortex only: proximal and distal tubule
 Cortex and outer medulla: loop of Henle
 Cortex, outer, and inner medulla: collecting tubule
o Juxtamedullary (long looped) nephron
 Cortex only: proximal and distal tubule
 Cortex, outer, and inner medulla: loop of Henle and collecting tube

Question 29

How do we distinguish between cortical and juxtamedullary nephrons; what are the relative proportions of these nephron sub sets in the human kidney?

Answer 29

o Cortical and juxtamedullary nephrons are distinguished by presence of the loop of Henle in the inner medulla. Juxtamedullary nephrons loop of Henle descends down into the inner medulla and cortical nephrons do not.
o 80% of nephrons are cortical and 20% are juxtamedullary

Question 30

What does the percentage of juxtamedullary (long-looped) nephrons appear to correlate with across species?

Answer 30

The greater the percent of juxtamedullary nephrons present in the kidney the greater the ability of that species to concentrate urine.

Question 31

What is unique about the vascular arrangement surrounding the glomerulus?

Answer 31

o Systemic vasculature anatomy contains afferent arteries, capillary beds, and efferent veins
o Renal vasculature anatomy contains afferent arteries, capillary beds, and efferent arteries

Question 32

Why is this arrangement important for glomerular filtration?

Answer 32

o Having an afferent and efferent arteriole allows the renal vasculature to control hydrostatic pressure at the glomerulus which controls filtration

Question 33

What are peritubular capillaries and what is/are their function?

Answer 33

In the renal system, peritubular capillaries are tiny blood vessels that travel alongside nephrons allowing reabsorption and secretion between blood and the inner lumen of the nephron. Peritubular capillaries surround the proximal and distal tubules, as well as the loop of Henle, where they are known as vasa recta.

Question 34

What are the vasa recta, and why are they so critical to renal concentrating capacity?

Answer 34

o Vasa recta are capillary beds that extend down into the medulla next to the juxtamedullary nephron’s loop of Henle.
o They affect the hyper tonicity of urine through water regulation

Question 35

What percentage of cardiac output is delivered to the kidney?

Answer 35

Kidneys receive 25% of cardiac output (1.2-1.5 L/min)

Question 36

How does renal oxygen consumption compare with other organs?

Answer 36

Renal oxygen concentration is low suggesting that renal oxygen consumption is low

Question 37

Why does analysis of an arterio-venous O2 concentration difference alone give a deceptive idea of renal O2 consumption?

Answer 37

This is false, renal blood flow is greater than other organs causing more oxygen to be consumed over time. Measuring static oxygen concentration is misleading.

Question 38

How is renal oxygen consumption calculated?

Answer 38

O2 consumption = a-v O2 difference X blood flow rate

Question 39

Explain the relationship between renal blood flow and renal O2 consumption

Answer 39

This paradox is explained by the fact that since blood flow to the kidneys is high (column 2).. Therefore only a relatively low extraction % is required to provide O2 needs (O2 consumption = a-v O2 difference X blood flow rate)

Question 40

What are the three principal elements of renal function?

Answer 40

Glomerular filtration- plasma filtered from glomerular capillaries into Bowman’s space
o Tubular reabsorption- movement from lumen into the peritubular capillary
o Tubular secretion- movement of a substance from the peritubular capillary into the lumen

Question 41

What is the filtration fraction and a filtered load?

Answer 41

o Filtration fraction- 20% of total blood plasma that enters the glomerular capillary that is actually filtered  filtration fraction = glomerular filtration rate (GFR) /renal plasma flow rate (RPF)
o Filtered load- what is the concentration of solutes in the glomerular capillary  filtered load = glomerular filtration rate (GFR) x plasma concentration (Px)

Question 42

What is the significance of tubular secretion for the maintenance of body fluid homeostasis?

Answer 42

Secretion is mainly to recover solutes that are poorly filtered due to size, charge, or protein binding.
o Molecules >5000 Da and/or negative charge are poorly filtered at glomerulus and require secretion (ex. proteins)
o If secretion did not recover large molecules they would be excreted in the urine resulting in hypotonic blood plasma. The kidney would excrete water in an attempt to reach homeostasis.

Question 43

Can you draw conclusions about renal function simply from the concentration of substances in the urine?

Answer 43

Proteins, amino acids etc. in the urine suggestive of impaired renal function ii. Urine flow rate must be known to draw conclusions about excretory capacity

Question 44

How is urine shunted from the kidney to the bladder?

Answer 44

o Walls of calices, pelvis, and ureters contain smooth muscle with inherent pacemaker activity
o Calices initiates peristaltic contraction moving urine from kidney to the bladder

Question 45

What is the micturition reflex; what is the voluntary component of this reflex?

Answer 45

o Micturition reflex-
 Parasympathetic afferent neurons in bladder muscle respond to stretch as bladder fills with urine.
 Impulse travels parasympathetic pathways to brain and returns as parasympathetic efferent impulse that activates bladder muscle contraction
 Involuntary
o Voluntary component
 Skeletal motor neuron under voluntary control innervates external sphincter that allows urine to exit the neck of the bladder into the posterior urethra

Question 46

Identify common abnormalities of micturition.

Answer 46

i. Automatic bladder … spinal cord damage above the sacral region - loss of higher center control (particularly suppression) of the micturition reflex … periodic unintended bladder emptying
ii. Atonic bladder … loss of sensory nerve fibers therefore no micturition reflex … bladder overflows a few drops at a time … overflow incontinence

Question 47

What are the principal structural components of the filtration barrier?

Answer 47

Endothelium (fenestrated)
Basement membrane (collagen, laminin, fibronectin)
Epithelium (podocytes)

Question 48

What are the potential functions of mesangial cells?

Answer 48

o Mesangial cells are interspersed between the glomerular capillaries
 Provide structural support for capillaries
 Secrete extracellular matrix
 Possess phagocyte activity
 Secrete prostaglandins and cytokines
 Possess contractile activity

Question 49

What are the principal factors that dictate “filterability” of a particular solute? How can the effects of these factors be illustrated?

Answer 49

Size and charge of the molecule.

?

Question 50

For a freely filterable solute, how will its concentration in Bowman’s space compare to that of plasma in the glomerular capillaries?

Answer 50

Freely filterable solute concentration in Bowman’s space and plasma of glomerular capillaries are identical. An isotonic relationship develops from the free passage of filterable solutes across the membrane in the glomerulus.

Question 51

What happens to the concentration of solutes in the plasma immediately downstream of the glomerulus (in the efferent arteriole) that are not freely filtered? Give examples

Answer 51

Proteins are not filtered across glomerular capillaries.
o Bowman’s glomerulus has no oncotic pressure because no proteins cross the filtration barrier.
o Oncotic pressure increases from afferent to efferent arteriole due to fluid loss across the filtration barrier into Bowman’s capsule resulting high protein plasma concentration

Question 52

What often happens to filterability in glomerular diseases?

Answer 52

?

Question 53

What are the principal forces involved in glomerular ultrafiltration?

Answer 53

o Starling forces (hydrostatic force) is the main filtration force of the glomerular capillary
o Bowman’s space hydrostatic pressure and glomerular capillary oncotic pressure are the forces opposing filtration

Question 54

What is the difference between oncotic and osmotic pressure?

Answer 54

.o Osmotic pressure-a hydrostatic pressure caused by a difference in the amounts of solutes between solutions that are separated by a semi-permeable membrane.
o Oncotic pressure- osmotic pressure due to protein

Question 55

What is a filtration coefficient?

Answer 55

1. a measure of a membrane’s permeability to water; specifically, the volume of fluid filtered in unit time through a unit area of membrane per unit pressure difference, taking into account both hydraulic and osmotic pressures.

Question 56

How do these forces differ from those in systemic capillaries?

Answer 56

.o Hydrostatic force across the glomerular capillary maintains constant from afferent to efferent
o Hydrostatic force at the systemic capillary is high at the arteriole pushing fluid into the interstitial space and low at the vein reversing the flow of fluid from the interstitial space into the vein

Question 57

What are some of the causes of localized systemic edema?

Answer 57

.o Altered balance of starling forces across the systemic capillaries resulting in an influx of fluid into the interstitial space

Question 58

Why does capillary hydrostatic pressure remain relatively constant in glomerular capillaries?

Answer 58

.o There are resistance points at both the afferent and efferent ends of the glomerular capillaries that maintain the hydrostatic pressure

Question 59

Why does oncotic pressure increase along the glomerular capillary?

Answer 59

.o As fluid is filtered from the glomerular capillary to the renal tubule the plasma within the capillary becomes more concentrated because proteins do not cross the filtration barrier. Oncotic pressure increases because protein concentration is higher in the glomerular capillary than in the tubular fluid.

Question 60

When is an NFP of zero achieved? What is filtration pressure equilibrium and disequilibrium?

Answer 60

.o When glomerular capillary oncotic pressure increases to the point where glomerular capillary hydrostatic pressure is equal to Bowman’s space hydrostatic pressure
 Trace the pressure profile along the renal vasculature.
o Systemic BP is highest
o Glomeruli plasma pressure drops slightly after afferent arteriole resistance is passed
o Renal plasma pressure drops further after efferent resistance is passed
o Renal plasma pressure is lowest at the peritubular arteriole

Question 61

Why is hydrostatic pressure so low by the time the peritubular capillaries are reached?

Answer 61

.The two resistance points before and after Bowman’s capsule result in a low hydrostatic pressure when the blood plasma reaches the periotubular capillaries

Question 62

How does the ultrafiltration coefficient compare in glomerular and systemic capillaries?

Answer 62

.o The filtration coefficient of a semipermeable membrane o Glomerular capillary ultrafiltration coefficient is much higher than in systemic capillaries

Question 63

We estimate that the entire plasma volume is filtered 60 times a day; why is this important?

Answer 63

.Constant filtration of the plasma every 24 hours ensures removal of wastes, reabsorption of important solutes, reabsorption of water, resulting in maintenance of homeostasis

Question 64

What happens to glomerular filtration rate and renal blood flow (and why) with selected changes in diameter of the afferent or efferent arteriole?

Answer 64

.see chart in objectives

Question 65

What are the principal factors involved in physiological regulation of glomerular filtration? Where do they act?

Answer 65

.o GFR is physiologically regulated by changing the resistance (diameter) of the afferent arteriole using
 Vasoconstriction of afferent arterioles through sympathetic renal nerves to reduce GFR
 Vasoconstriction of afferent and efferent arterioles through angiotensin II

Question 66

What is the role of vasodilatory prostaglandins in the regulation of glomerular filtration?

Answer 66

.o Vasodilatory prostaglandins PGE2 and PGI2 (prostacyclin)
 Decrease in BP = increase in sympathetic nerve activity and angiotensin II activation which stimulates prostaglandins
 Increase production of angiotensin II up-regulates PGE2 and PGI2 synthesis
 Prostaglandins modulate sympathetic nervous system vasoconstriction through vasodilation of the afferent arteriole

Question 67

What do you predict would happen to glomerular filtration and renal blood flow if, for example NSAID’s were given at a time of high sympathetic nerve activity?

Answer 67

.High sympathetic nerve activity would already cause a state of vasoconstriction at the glomerular arteriole
o NSAID’s (indomethacin) inhibit prostaglandin synthesis, no vasodilation
o Lack of prostaglandins removes the modulating control for vasoconstriction allowing increased vasoconstriction at the glomerular arteriole via angiotensin II
o Acute renal failure results

Question 68

What is meant by “pre-renal” acute renal failure?

Answer 68

.

Question 69

What are some of the factors that can adversely affect glomerular filtration?

Answer 69

.o Changes to the ultrafiltration coefficient (Kf)
 Glomerular disease
 Mesangial cell contractility
o Changes in capillary oncotic pressure
 Alteration of plasma protein concentration
o Changes in intra-tubular pressure
 Ureteral obstruction by stone
 Kidney can protect itself through ureterorenal reflex that lowers GFR

Question 70

Why could mesangial cell contractility potentially affect GFR?

Answer 70

.

Question 71

Could ureteral obstruction stop glomerular filtration completely? Explain in terms of Starling forces.

Answer 71

.Yes, complete post renal obstruction increases glomeruli pressure enough to result in damage to the glomerulus. The increase in pressure results in sympathetic activity causing increased constriction at the afferent arteriole inhibiting fluid flow to the glomerulus.

Question 72

What is the ureterorenal reflex?

Answer 72

Ureteral obstruction (ureteral stone) > reflex constriction> sympathetic reflex> renal arteriole constriction> reduction of glomerular filtration rate

Question 73

What is meant by autoregulation of glomerular filtration (and renal blood flow)?

Answer 73

The kidneys intrinsic ability to maintain GFR and renal plasma flow consistently over a wide range of blood pressures (70 mmHg and greater)

Question 74

Why do we know that it is an intrinsic (intrarenal) mechanism?

Answer 74

Mechanism must be intrinsic because it can be observed in
 Transplanted kidneys that are not connected to the donors sympathetic nervous system
 Isolated perfused kidneys exhibit this ability in vitro with no hormonal input

Question 75

Why do we know that the afferent arteriole is the control site?

Answer 75

.o The afferent arteriole pressure is the primary determinant for glomerular filtration
o Resistance changes in the afferent arteriole parallel glomerular filtration rate GFR and the rate of plasma filtration RPF

Question 76

What is the importance of renal autoregulation?

Answer 76

.Autoregulation prevents fluctuations in GFR and RPF

o Prevents large changes in water and solute excretion as arteriole pressure changes

Question 77

What is the myogenic theory of renal autoregulation.

Answer 77

.o Reflex resistance changes in the afferent arteriole

o BP increases causing dilation of the afferent arteriole reducing the changes in glomerular arteriole pressure

Question 78

What is the tubuloglomerular (TG) feedback theory of renal autoregulation?

Answer 78

.o A change in flow rate and or composition of tubular fluid sensed at the macula densa causes a compensatory change in glomerular flow rate
o BP increases causing increase in glomerular arteriole pressure which increases glomerular flow rate subsequently increasing tubular fluid flow resulting in constriction of the afferent arteriole and minimal increase in glomerular arteriole pressure or glomerular flow rate.
o A feedback mechanism that relies on the proximity of the renal tubule to the macula densa

Question 79

What is the macula densa and what is its role in TG feedback?

Answer 79

.

o A feedback mechanism that relies on the proximity of the renal tubule to the macula densa

Question 80

Why is it important to understand that autoregulation can be overridden when homeostatically necessary? Work through an example such as the response to hemorrhage; would autoregulation make sense under these conditions?

Answer 80

.Auto-regulation is not desirable in all circumstances
o During hemorrhage BP drops
 Auto-regulation would result in a dilation of afferent arteriole in an attempt to maintain glomerular filtration rate increasing blood flow in the kidney that would further decrease systemic BP
 Override of auto-regulation results in constriction of the afferent arteriole reducing glomerular filtration rate resulting in water conservation and maintenance of blood volume
 By overriding auto-regulation the body can attempt to maintain systemic BP and shunt blood from the kidney to vital organs such as the brain and heart