Physiology Exam 4: Renal Physiology

Front 1

What is the primary function of the kidney?

Back 1

Control the volume and composition of the ECF

Front 2

What are some conditions that can be caused by abnormal kidney function?

Back 2

- weakness: increased plasma osmolarity

- vomition

- coma: can't get rid of acids

- polypnea- respiratory compensation of acidosis

- muscle twitching- swelling in the central nervous system

- cardiac weakness- elevated potassium

- uremia- leakage of unsecreted urea into blood

Front 3

What are some responsiblities of the kidneys?

Back 3

1. regulate fluid and volume composition

2. regulate fluid osmolarity and pH

3. regulation of body metabolites

4. regulation of urea

5. regulation of erythropoietin

6. production of renin

7. regulation of vitamin D

8. elimination of foreign substances

Front 4

What are the four mechanisms of movement in the formation of urine?

Back 4

1. filtration

2. reabsorption

3. secretion

4. excretion

Front 5

define filtration

Back 5

the initial moment of fluid and solute from the blood to Bowman's space through a series of membranes from an area of high pressure to lower pressure

Front 6

define reabsorption

Back 6

describes a direction of movement from kidney tubule into interstitial space and back into capillaries

Front 7

define secretion

Back 7

describes a direction of movement from capillaries to kidney tubules

Front 8

define excretion

Back 8

final production of urine. Anything that has been filtered and/or secreted and not reabsorbed will be excreted

Front 9

What is the Donnan effect?

Back 9

describes the fact that the filtrate in Bowman's space has more negative ions and fewer positive ions than plasma

Front 10

What factors affect the filtration of molecules in the kidney?

Back 10

- osmotic pressure

- membrane pore size

- net pressure difference

Front 11

What is the functional unit of the kidney?

Back 11

nephron

Front 12

In which part of the kidney are the glomeruli located?

Back 12

cortex

Front 13

what is a glomerulus

Back 13

A web of capillareis that sit inside Bowman's capsule and provide plasma to be filtered by the kidneys

Front 14

List in order the structures through which potential urine passes in the kidney

Back 14

Renal corpuscle

proximal convoluted tubule

thick descending limb of LH

thin descending limb of LH

thin ascending limb of LH

thick ascending limb of LH

distal convoluted tubule

collecting duct

Front 15

What are the layers of the renal corpuscle through which filtrate must pass (in order)

Back 15

1. fenestrated capillary endothelium

2. basement layer

3. visceral epithelium/ podocyte layer

Front 16

Which layer of the renal corpuscle does filtrate actually pass "through" as opposed to between?

Back 16

basement layer

Front 17

which layer of the renal corpuscle provides the most resistance to filtrate movement?

Back 17

podocyte layer

Front 18

What is the relationship between body weight and GFR? Number of glomeruli?

Back 18

as body weight increases

- GFR increases

- number of glomeruli increase

- diameter of glomeruli increase

Front 19

What structures are part of the juxtaglomerular apparatus?

Back 19

- macula dense of distal convoluted tubule

- juxtaglomerular cells of afferent arterioles

- efferent arteriole

- extraglomerular mesengial cells

Front 20

Would you expect a frog or camel to have longer loops of henle? Why?

Back 20

camel

the loop length is associated with ability to concentrate urine. Because the camel lives where there is less access to water it would need to be able to concentrate its urine more and would therefore have longer loops that descend further into the medulla

Front 21

What physical property of the loop of Henle makes it important in the concentration of urine?

Back 21

Hairpin loop at distal end forms a countercurrent flow system

Front 22

What is a portal system?

Back 22

Arterioles and venules connected by a series of 2 capillary beds

Front 23

What are the 2 capillary beds that compose the renal portal system?

Back 23

glomerular capillary bed and peritubular capillaries

Front 24

What is the vasa recta?

Back 24

part of the peritubular capillaries that serve the juxtamedular nephrons (long loops of Henle) and participate in the countercurrent exchange mechanism

Front 25

Is the kidney served by sympathetic nerve fibers, parasympathetic nerve fibers, or both?

Back 25

sympathetic

Front 26

What is the primary vasomotor function of sympathetic nerves? how would this affect GFR?

Back 26

vasoconstrictive

- if they constrict the afferent arteriole it would decrease GFR

- if they constrict the efferent arteriole it would increase GFR

Front 27

What is the equation for filtration fraction?

Back 27

GFR/RPF

Front 28

What factors must be considered when determining filtration in the glomerulus?

Back 28

Starlings forces:

- Hydrostatic pressure in glomerular capillary

- plasma oncotic pressure

- hydrostatic pressure in Bowman's space

- oncotic pressure in bowman's space

Front 29

How do Starling's forces differ between the glomerulus and extra-renal capillaries?

Back 29

- hydrostatic pressure in glomerular capillary remains nearly constant as blood flows through but in extra-renal capillaries the pressure decreases

- pressure is much higher in glomerular capillary

- glomerular capillary is less permeable to protein than extra-renal capillaries

Front 30

How does oncotic pressure change as blood flows through the glomerulus?

Back 30

increases due to lower permeability to proteins (water can move out but proteins cannot so they become concentrated increasing the oncotic pressure)

Front 31

what is the greatest driving force for filtration?

Back 31

net hydrostatic pressure difference between glomerular capillary and inside of bowman's space

Front 32

How does pressure change as you move along the nephron

Back 32

decreases

at the renal pelvis it is virtually zero

Front 33

What affect would ligation of a ureter have on renal filtration rate?

Back 33

ligation of a ureter would cause a back up of pressure.

This would decrease the pressure difference between bowman's space and glomerular capillaries decreasing GFR

Front 34

What is clearance?

Back 34

it describes the kidney's ability to remove a substance from the plasma in a given period of time.

clearance= urine load/ plasma concentration

Front 35

If a substance was "cleared" how did it move into the tubular lumen? (was it filtered or secreted)

Back 35

either. clearance does not designate how it was moved just that it entered the tubular lumen

Front 36

define urine load

Back 36

urine flow x urine concentration of substance

Front 37

what does freely filtered mean?

Back 37

the amount of the substance is the same in Bowman's space and plasma

Front 38

Define glomerular filtration rate

Back 38

the rate at which a filtrate is formed in both kidneys per minute

Front 39

what are qualities necessary for a substance to be used as a marker for calculating glomerular filtration rate?

Back 39

a. freely filtered

b. neither reabsorbed or secreted

c. easily measured in both plasma and urine

d. neither synthesized or metabolized by the kidneys

e. not directly effect GFR

Front 40

What are two common substances used as markers? How are each administered?

Back 40

- inulin- injected

- creatinine- produced by the body so does not have to be administered

Front 41

Describe the relationship between the clearance of inuline and GFR.

Back 41

they are the same. Because inulin is neither secreted or absorbed and not synthesized or metabolized in the kidney, what is present in the urine is what was filtered. Therefore, the rate at which it is cleared is approximately equal to the GFR

Front 42

What affect does alteration of plasma concentration of inulin or urine flow rate have on the calculation of its clearance/ GFR?

Back 42

no effect

GFR is independent of the urine flow rate and the plasma concentration of a marker

- as plasma concentration increases, urine concentration increases--> same value of GFR

- as flow rate increases, urine concentration decreases--> same value for GFR

GFR= (flow rate x urine concentration)/ plasma concentration

Front 43

how does the clearance of creatinine compare to that of inulin? Explain the difference

Back 43

it is slightly higher creatinine is secreted to some degree

Front 44

define azotemia

Back 44

increase of nitrogenous molecules (such as creatinine and urea) in the blood

Front 45

Describe the 3 types of azotemia.

Back 45

prerenal- decreased blood flow to kidneys results in fewer nitrogenous molecules being filtered

renal- compromised filtering process due to kidney tissue damage causes the increase

post renal- blockage of low of urine after the kidney leads to a back up in the system and decreased filtration

Front 46

How can inulin be used to calculate the percentage of water reabsorbed by the kidneys?

Back 46

1-([inulin in plasma]/[inulin in tubular fluid])

inulin is freely filtered so the amount of inulin is the same in the tubular fluid and plasma. The concentration however differs due to the reabsorption of water. By comparing the concentrations using the equation above you can determine the percent of water that has been reabsorbed at any point in the nephron

Front 47

define filtration fraction

Back 47

the percentage of the total plasma entering the kidneys that actually becomes filtrate

Front 48

what is the equation for extraction ratio?

Back 48

E= (Pa -Pv)/ Pa

extraction ratio is the ratio of the concentration of a marker in the arteries and veins

it is used to calculate corrected Renal plasma flow

Front 49

what is the equation for corrected renal plasma flow?

Back 49

Clearance of marker (e.g. PAH)/ extraction ratio

Front 50

What is the equation for renal blood flow?

Back 50

RBF= RPF/ (1-Hct)

Front 51

what is the difference between primary active transport and secondary active transport?

Back 51

primary- transport is coupled directly to the hydrolysis of ATP

secondary- transport of one molecule against its concentration gradient is linked to the movement of another molecule along its concentration gradient

Front 52

how can the amount of a substance reabsorbed be quantified in relation to amount filtered and excreted?

Back 52

Amount reabsorbed= amount filtered - amount excreted

Front 53

how can you calculate the amount of a substance that is filtered (filtered load)?

Back 53

filtered load= GFR x [substance in plasma]

Front 54

What 5 things must be known to calculate the amount of glucose (or any substance) reabsorbed?

Back 54

1. urine concentration of inulin (for determining GFR)

2. urine flow rate (for determining GFR)

3. Plasma concentration of inulin (GFR)

4. urine concentration of glucose

5. plasma concentration of glucose

Front 55

What major feature describes a molecule whose reabsorption is limited by a transport maximum?

Back 55

it is actively transported using some transport system (pump)

Front 56

What limits a molecule's reabsorption if it is a transport maximum molecule?

Back 56

saturation of carrier proteins and enzymes

Front 57

What happens if there is more of a transport maximum molecule than can be handled by transport proteins?

Back 57

it will "spill" over into the urine

- it will not all be reabsorbed

Front 58

What is plasma threshold?

Back 58

the concentration of a transport maximum molecule in plasma when that molecule first appears in the urine

- the concentration in plasma when the carrier molecules become saturated

Front 59

What is splay?

Back 59

When graphing the reabsorption of transport maximum molecules there is initially a positive linear slope followed by a flattening of the curve when the transporter becomes saturated.

The transition between these two segments is rounded and not a sudden change- this is referred to as splay.

Splay is due to the fact that each nephron has a different transport maximum depending on the number a capacity of transport proteins and enzymes.

Front 60

glucose, fructose, and xylose all use the same transport protein in the nephron. If they are all present in the tubular lumen at the same concentration which is mostly likely to be reabsorbed?

Back 60

glucose

Front 61

How is sodium transported first into tubular cells from the tubular lumen and then out of the cells.

Back 61

sodium moves passively into cells along electrochemical gradient (less sodium inside the cell and inside the cell has more negative charge)

sodium is actively pumped out of the cell into the lateral intercellular spaces

Front 62

Time and gradient dependent reabsorption

Back 62

passive reabsorption depends on the amount of time that fluid is in the tubules and the concentration gradient of the molecule to be transported

Front 63

What are some examples of molecules that are passively reabsorbed based on a time and gradient dependent mechanism?

Back 63

chloride

urea

passive diffusion of sodium into tubular cell

Front 64

if urine flow rate increases, how does that affect urea reabsorption

Back 64

reabsorption decreases and excretion increases.

the faster the fluid moves through the less time there is for reabsorption. As less water is reabsorbed the concentration gradient for urea is not favorable for transport out of the tubules

Front 65

Describe the process for the isotonic reabsorption of water in the proximal convoluted tubule.

Back 65

1. sodium is actively pumped into intercellular spaces and chloride follows

2. the increased solute concentration draws water into the spaces

3. the increased osmotic pressure causes water and the solutes to move out of the intercellular spaces and into the peritubular space

4. the high oncotic pressure in the peritubular capillaries draws water from the peritubular space into the capillaries

Front 66

What are the 3 categories of secreted substances in the urine?

Back 66

1. active secretion with transport maximum limited capacity

2. active section with gradient- time limited capacity

3. passive transport down electrical or chemical gradients

Front 67

How can quantity secreted be expressed in terms of quantity excreted and quantity filtered?

Back 67

quantity secreted= quantity excreted - quantity filtered

Front 68

What 5 things must be known to determine quantity secreted?

Back 68

1. urine concentration of inulin (for GFR)

2. urine flow rate (for GFR)

3. plasma concentration of inulin (for GFR)

4. urine concentration of PAH

5. plasma concentration of PAH

Front 69

Which of the three categories of secretion mechanisms describes the secretion of PAH?

Back 69

PAH is secreted on a Transport maximum basis

Front 70

What are the functions of renal blood flow?

Back 70

1. deliver oxygen, nutrients, and hormones to the cells of the nephron

2. return carbon dioxide and reabsorbed water and solutes to general circulation

3. determine glomerular filtration rate

4. modify the rate of solute and water reabsorption by the nephron

5. play a role in the concentration and dilution of urine

Front 71

The sympathetic nervous system has vasoconstrictive actions. If it is activated and constricts the afferent arterioles, how would this affect GFR and RBF? What if it constricted the efferent arteriole?

Back 71

Afferent- decrease both GFR and RBF

--if the afferent arteriole is constricted, less blood will be getting to glomerulus so there will be less filtered

Efferent- increase GFR, decrease RBF

- by constricting the efferent arteriole, there is a build up of blood in the glomerulus. This means there is more to be filtered but it leads to a back up that decreases total RBF

Front 72

An increase in blood pressure is a major threat to homeostasis in the kidney. How does the kidney maintain normal flow if blood pressure is increased?

Back 72

increase resistance

flow= pressure difference/resistence

Front 73

RBF is much higher in the renal cortex (340ml/100g/min) than in the papilla (2.5 ml/100g/min). What determines this difference in flow?

Back 73

differing resistances in the different sections

Front 74

If you suspected that a patient was hemorrhaging internally and you decided to test this by measuring distribution of renal blood flow where would expect to see blood flow increased or decreased?

Back 74

- increased blood flow to the medulla where water and solutes are reabsorbed (loosing blood = loosing ECF and solutes so you want to get as much back as possible)

- decreased blood flow to the cortex where water and solutes are filtered out (don't want to loose more than you already are)

Front 75

What affect would an infusion of NaCl solution have on renal blood flow?

Back 75

This hypertonic solution would increase renal blood flow by expanding ECF volume (increases blood pressure)

over time though the extra sodium would be excreted and renal blood flow would return to normal

Front 76

I just ran a half marathon that took me 1 hour and 35 minutes (YAY ME!) luckily I didn't have to stop to pee the whole time even though I drank water before and during the race. Why is this?

Back 76

during exercise renal blood flow is markedly decreased which means less filtrate is formed so urine flow rate decreases

Front 77

Mesangial cells are known mainly for their function in supporting phagocytic cells in the nephron. How are they also involved in regulation of renal blood flow?

Back 77

In addition to the mesangial matrix which supports the phagocytic cells they secrete prostaglandins and cytokines which can affect constriction/dilation of renal capillaries and therefore alter renal blood flow

Front 78

What is auto regulation and in what part of the kidney is it seen?

Back 78

autoregulation is the process whereby the kidney maintains a relatively constant blood flow and GFR in the face of external changes in pressure.

this is only a property of the cortex

Front 79

What 2 theories did we discuss to explain auto regulation of the kidney?

Back 79

myogenic effect - respond to stretch

tubuloglomerular feedback- respond to chemical composition of urine

Front 80

What is the difference between the afferent arteriolar vasoconstrictor feedback mechanism and the efferent arteriolar vasoconstrictor feedback mechanism?

Back 80

- both involve the juxtaglomerular apparatus sensing low solute concentration and therefore responding by increasing GFR

- AFFERENT- the juxtaglomerular apparatus releases vasodilators that act on the afferent arteriole to increase RBF

- EFFERENT: the juxtaglomerular apparatus releases renin which leads to the formation of angiotensin II which is more active at the efferent arterioles and causes vasoconstriction leading to increased pressure and increased GFR

Front 81

What adverse effect could occur if angiotensin II's effects on the kidneys were unregulated? What molecules can be used to counteract the effects of angiotensin II?

Back 81

angiotensin II leads to decreased RBF due to vasoconstriction which if prolonged could lead to damaging ischemic effects.

prostaglandins and ANP have effects that counteract those of angiotensin II by causing dilation of blood vessels

Front 82

What are the 5 important activities of circulating ANP?

Back 82

1. vasodilation of afferent and constriction of efferent arterioles--> decrease blood pressure

2. inhibits renin release

3. inhibits secretion of aldosterone

4. inhibits reabsorption of NaCl in the collecting duct

5. inhibits ADH secretion

*promotes excretion of Na and water to effectively decrease blood pressure

Front 83

where is renin synthesized and stored?

Back 83

juxtaglomerular cells in the afferent and efferent arterioles as prorenin

Front 84

What 3 mechanisms are important in the regulation of renin secretion?

Back 84

1. intrarenal receptors: vascular baroreceptors and the macula densa

2. the renal sympathetic nerves

3. humoral agents including prostaglandins

Front 85

Where are the intrarenal baroreceptors located?

Back 85

in the afferent arteriole

Front 86

Would a pressure increase in the afferent arteriole sensed by the baroreceptors trigger renin secretion or inhibit it?

Back 86

inhibit

the RAAS system functions to increase blood pressure so if it is already high or is going up you don't want more renin

Front 87

how does an increase in sodium concentration in tubular fluid affect the secretion of renin?

Back 87

sodium concentration and renin release are inversely related

i.e. an increase in sodium concentration would cause a decrease in renin release

- Na concentration would increase when there is less water in the blood. if there is less water renin will lead to a cascade that will increase the amount of water present

Front 88

does sympathetic nerve stimulation seem to trigger or inhibit renin release?

Back 88

trigger

Front 89

Would you be more likely to see renal papilla in the kidneys of kangaroo rats or newts? Why?

Back 89

kangaroo rats

renal papilla are formed by long looped nephrons which are only present or present to a greater degree in animals that live in dry climates

Front 90

What are some stimuli for ADH release?

Back 90

- increase in plasma osmolality

- pain

- fear

- low blood pressure

Front 91

Where are the osmoreceptors responsible for ADH release located?

Back 91

hypothalums

Front 92

increased ADH levels have what effect on urine production

Back 92

increased ADH= decreased urine production

Front 93

What is the mechanism by which diabetes mellitus causes polyuria?

Back 93

- body can't use glucose

- glucose accumulates in blood and is freely filtered by kidneys

- increased glucose concatenation in nephron draws more water in increasing volume of urine produced

Front 94

What is the mechanism by which diabetes insipidis causes polyuria?

Back 94

There is a disruption in the mechanism of release of ADH

without ADH water is not reabsorbed from the distal convoluted tubule and volume of urine increases

Front 95

What is the mechanism by which nephrogenic diabetes causes polyuria?

Back 95

ADH is released normally but is unable to act on the kidneys resulting in the increased volume of urine.

Front 96

Which part of the nephron is ALWAYS impermeable to water?

Back 96

thick portion of ascending limb of loop of henle

Front 97

Describe the proposed mechanism of action of ADH on renal nephrons?

Back 97

2 functions: increase NaCl reabsorption from thick ascending limb and increase permeability of collecting duct to water and urea

- attaches to basolateral membrane

- increases intracellular cAMP

- activates protein kinases

- increase presence of aquaporins into luminal membrane

Front 98

The production of hyposmotic urine requires that ________ be reabsorbed while _________ remains in the tubule.

In which portions of the nephron is this accomplished?

Back 98

The production of hyposmotic urine requires that SOLUTE be reabsorbed while WATER remains in the tubule.

This is possible in the ascending limb of the loop of henle, the DCT, and the collecting duct

Front 99

understand how the osmotic gradient in the interstitium is created

Back 99

i don't have room to explain it fully here but you should know it. briefly...

- in the descending limb of the loop of henle the tubular fluid equilibrates with the interstitium by pumping out water and taking in NaCl

- in the ascending limb solute is pumped out but water can't follow creating a gradient within the interstitium

- later in the collecting duct, if ADH is present, water moves out in the proximal portion causing a gradient of urea to form that leads to it being pumped out in the distal duct

- all of this leads to a higher concentration in the distal medullary interstitum and the longer the tubule the larger the gradient

Front 100

Which part of the nephron is called the diluting segment? Why?

Back 100

the ascending limb of the loop of Henle because this is where hyposmotic urine is created.

solute is pumped out of this region but it is impermeable to water so it cannot follow resulting in urine that is hyposmotic to plasma

Front 101

Describe the movement of water and solute in the descending and ascending portions of the vasa recta.

Back 101

descending: water leaves and solute enters

ascending: water enters and solute leaves

Front 102

what is the significance of the vasa recta

Back 102

normally blood vessels would make one trip through a tissue in one direction and equilibrate along their path.

If this happened in the kidney, water would move out of the capillaries and solute would move in and this would dilute the medullary interstitium and disrupt the important osmotic gradient.

because the vasa recta form a countercurrent exchange both descending and ascending this problems is avoided because what is taken out going down is put back in going up

Front 103

What are the major extracellular ions?

Back 103

sodium and chloride

Front 104

What are the consequences of increased and decreased salt load in the body?

Back 104

increased: hypertension and edema (more water is drawn into the blood vessels due to the higher salt concentration

decreased: hypotension and dehydration

Front 105

In what part of the nephron is most NaCl reabsorbed?

Back 105

Proximal tubule (67%)

Front 106

what is solvent drag?

Back 106

Water follows the reabsorption of sodium in the proximal tubule and other molecules such as potassium and calcium are pulled along with water. The passive movement of these other molecules is solvent drag

Front 107

Describe the movement of sodium (transcellular or pericellular) in the proximal convoluted tubule.

Back 107

in the proximal PCT it is all transcellular

- passively moves into the cell usually along with other solutes such as glucose and amino acids and is actively pumped out

in distal PCT it is both transcellular (70%) and paracellular (30%)

Front 108

What conditions in the distal proximal convoluted tubule allow for the passive paracellular movement of sodium?

Back 108

there is an increased chloride concentration within the cell which gives the lumen a net positive charge. This charge establishes an electrical gradient that favors the passive movement of sodium through the tight junctions between cells

Front 109

How is sodium reabsorbed in the ascending loop of Henle?

Back 109

1. a symporter that also transports 2Cl and 1 K. Of these, potassium is the only ion moving against its gradient

2. an antiproton that pumps hydrogen into the lumen

Front 110

What is the electrical gradient in the loop of Henle? How is it established and what is the result?

Back 110

positive in lumen, negative in cell

sodium is pumped into cell then moved into the pericellular space while hydrogen ions are pumped into the lumen. This increases the positive charge in the lumen along with loosing positives within the cell.

this results in the uptake of Mg, Ca, and K through both transcellular and pericellular pathways

Front 111

What are the 2 types of cells in the DCT? What are their functions?

Back 111

1. principal cells- reabsorb sodium and water, secrete potassium

2. intercalated cells- secreted hydrogen and reabsorb bicarbonate and potassium

Front 112

What are the extra-renal adjustments for sodium balance in the kidneys?

Back 112

- release of hormones (ANP, angiotensin II, aldosterone, ADH, prostaglandins)

- alteration of sympathetic nerve activity

Front 113

How does stimulation/inhibition of the sympathetic nervous system affect sodium regulation in the kidneys?

Back 113

stimulation- increases reabsorption of NaCl

inhibition- decreases reabsorption of NaCl

Front 114

How would constriction of the efferent arterioles affect sodium balance?

Back 114

constriction of efferent arterioles would increase GFR

an increase in GFR would cause a serious loss of sodium

Front 115

What is meant by glomerulotubular balance?

Back 115

referes to mechanisms that maintain a balance between what the glomerulus does (filtration) and what the tubular system does (reabsorption)

i.e. mechanisms that match the amount of something that is filtered in the glomerulus to the amount that needs to be reabsorbed in the tubule (mechanism varies depending on what substance is being considered - glucose, sodium, water, etc)

Front 116

The glomerulotubular balance of sodium is likely due to what 3 things?

Back 116

- changes in Starling's forces of peritubular capillaries ( if GFR increases, oncotic pressure in capillaries increases which will lead to more sodium reabsorption)

- changes in geometry of tubules (possibly can increase or decrease reabsorption by altering surface area available for transport)

- reabsorption of glucose and amino acids (glucose and amino acids are Tm limited so they are limited by the amount of transport molecules, in many places sodium is linked to the transport of these molecules, so as more of them are reabsorbed, more sodium is reabsorbed)

Front 117

What are the two internal mechanisms for regulating sodium balance in the kidney?

Back 117

- glomerulotubular balance

- auto regulation of GFR

Front 118

What are the 3 methods (lines of defense) for regulating body pH?

Back 118

1st: chemical buffers in the blood (only free H+ contribute to pH so by binding to buffers pH is not altered as significantly

2nd: respiration

3rd: kidneys

Front 119

How do the kidneys help regulate body pH?

Back 119

secrete H+

reabsorb bicarbonate (important buffer in the blood)

Front 120

the kidneys cannot secrete urine with a really low pH; so how do they secrete H+ ions without lowering the pH of the urine?

Back 120

bind it to urinary buffers to form titratable acids or to ammonia to form ammonium

Front 121

Where is most bicarbonate reabsorbed in the kidney?

Back 121

PCT (90%)

10% in ascending loop of henle

Front 122

Describe how bicarbonate is reabsorbed from the kidneys

Back 122

1. within the cell carbon dioxide is hydrated to from carbonic acid which is then ionized to bicarbonate and H+

2. the H+ ions are secreted and combine with bicarbonate in the lumen to form CO2 and water

3. The bicarbonate is reabsorbed into the peritubular capillaries

effectively a bicarbonate is reabsorbed from the lumen but it is not the same one. One bicarbonate is lost in the lumen when it combines with the secreted H+ and one bicarbonate is moved into the capillaries from inside the cell.

Front 123

What are 4 factors that can influence bicarbonate reabsorption?

Back 123

- CO2 tension (as PCO2 increases HCO3 reabsorption increases)

- potassium concentration (as potassium ion concentration increases, HCO3 reabsorption decreases

- plasma chloride concentration ( as it increases, HCO3 reabsorption decreases

- adrenal corticosteroids

Front 124

What is non-ionic diffusion or diffusion trapping?

Back 124

the tubular cell membrane is highly permeable to ammonia (NH3) so it is easily secreted into the lumen.

in the lumen some of the H+ ions secreted by the tubular cell will bind to ammonia forming ammonium (NH4) which is not able to pass through the membrane

The effect is that ammonium, and with it a hydrogen ion, become trapped in the tubular lumen where they are eventually excreted in urine

Front 125

Describe potassium movement in the PCT, Loop of Henle, DCT, and collecting duct

Back 125

PCT: net reabsorption

loop of henle: net reabsorption

DCT: net secretion

collecting duct: can be secreted or reabsorbed depending on the amount in the diet

Front 126

the amount of potassium secreted in the distal convoluted tubule depends on what 3 things?

Back 126

1. transepithelial potential

2. concentration of intracellular potassium

3. power of potassium pumps

Front 127

How does tubular flow rate affect the amount of potassium excreted?

Back 127

increased flow of urine creates a sink for potassium which increases the amount of potassium excreted.

i.e. by rapidly removing (replenishing) tubular fluid there is always a large concentration gradient that will draw more potassium into the tubular lumen

Front 128

How does acid base status affect the amount of potassium excreted in the urine?

Back 128

acidosis: decreases excretion

- More hydrogen is present in cells which competes with intracellular potassium. if intracellular potassium is low there won't be a concentration gradient to move it out of the cell.

- acute acidosis inhibits the Na/ K pump

- acute acidosis decreases membrane permeability to potassium

Alkalosis: increases potassium excretion

- intercellular hydrogen decreases, this allows more potassium to take its place which creates a large concentration gradient to move potassium out of cell into urine

Front 129

What are some conditions that promote hyperkalemia?

Back 129

- metabolic acidosis, because less potassium is excreted

- exercise- potassium is released from skeletal muscle cells

- increase in ECF osmolarity: draws water into ECF which concentrates potassium in cells creating a concentration gradient that then causes it to move into the ECF as well

Front 130

In general, how do diuretics other than water and osmotic diuretics function

Back 130

prevent the establishment of normal ion gradients by tubular cells resulting in water not being reabsorbed as normal

Front 131

what are characteristics of osmotic diuretics?

Back 131

- freely filtered

- are only slightly reabsorbed

- pharmacologically inert

Front 132

Where do osmotic diuretics exert most of their function and what its their mode of action?

Back 132

inhibit reabsorption of water and sodium in the proximal tubule and loop of Henle

Front 133

Where are carbonic anhydrase inhibitor diuretics primarily active and what is their method of action?

Back 133

active mainly in the proximal tubule where carbonic anhydrase is most active

- prevent the hydration of carbon dioxide which leads to bicarbonate reabsorption. less bicarbonate reabsorption means it accumulates in the tubule and pulls water with it.

Front 134

site and method of action of loop diuretics?

Back 134

primarily active in the ascending loop of Henle

- blocks NaCl reabsorption by competing for Cl binding sites on Na/K/2Cl pump

- inhibits Mg and Ca reabsorption by disrupting the electrical gradient

- build up of these ions in the tubular fluid draws water in/prevents it from leaving

Front 135

site and method of action of thiazides (diuretics)

Back 135

primarily active in distal convoluted tubule

- inhibits reabsorption of NaCl by blocking NaCl symporter

- increase secretion of Na by increasing activity of NaCa antiporter

- increased excretion of potassium

Front 136

site and method of action of aldosterone antagonists

Back 136

primarily active in collecting duct

- block aldosterone receptor which leads to decreased sodium reabsorption and with that decreased water reabsorption

- interfere with sodium/potassium exchange leading to retention of potassium that would usually be secreted in exchange for sodium

Front 137

Give an example of each of the following types of diuretics:

- osmotic diuretic

- carbonic anhydrase inhibitor

- loop diuretic

- aldosterone antagonists

Back 137

- osmotic diuretic: mannitol

- carbonic anhydrase inhibitor: acetazolamide

- loop diuretic: furosemide

- aldosterone antagonist: spironolactone

Front 138

What are three roles hydrogen ions play in the body (three things that make it so important to regulate acid base balance)?

Back 138

1. hydrogen ions influence the structure and therefore function of proteins

2. hydrogen ions alter the distribution and activities of other body ions

3. hydrogen ions influence the activities of hormones and drugs

Front 139

How can pH imbalance lead to tetany?

Back 139

when pH increases (not enough H+), more calcium becomes bound to plasma proteins making less available in the free ionic form.

This decrease in ionic calcium alters the membrane potential of muscles cells making them more excitable and leading to tetany

Front 140

What is the difference between an acid and a base?

Back 140

Acid gives up hydrogen in solution, base takes on a hydrogen in solution

Front 141

Acid and bases are interchangeable molecules. An acid has a H+ bound (HA). its conjugate base is the same molecule without the hydrogen (A-).

Would you expect to see a weak acid exist more in its acid state (HA) or as its conjugate base (A-)?

Back 141

as the acid form (HA). Stronger acids will dissociate more fully in solution so you would see more of a strong acid unbound and more a weak acid bound.

- I think this seems tricky, but think of it as a measure of how well it does its job. Acids are supposed to give up hydrogens. Strong acids are really good at their job so give up their hydrogens easily and exist mostly as A-. Their conjugate base on the other hand is not good at its job of accepting H+ which is why it remains unbound as A-.

Front 142

Why is titratable acidity only considered a "potential acidity"?

Back 142

it measures bound H+ while in the body only free H+ contributes to pH so actual acidity only considers hydrogen ions in the ionic form

Front 143

what is the equation for pH

Back 143

1/[H+]

Front 144

Phosphoric acid has a pKa of 12.7. Is it a strong or weak acid? Would you expect its Ka to be high or low?

Back 144

weak, Ka would be very low

pKa= -log(Ka); low for strong acids, high for weak acids

Ka= [H+][conjugate base])/ [undissociated acid]

high for strong acids, low for weak acids)

Front 145

What is the Henderson Hasselbalch equation?

Back 145

pH= pK + (log ([A-]/[HA]))

Front 146

What is the difference between a volatile and nonvolatile acid?

Back 146

volatile acids are CO2 derived and can be expelled through respiration while nonvolatile acids cannot

Front 147

How do buffers limit the change in pH?

Back 147

,pH only takes into account free hydrogen ions.

buffers usually consist of a salt of a strong base. When mixed in solution with a strong acid the acid will dissociate increasing the amount of H+ but because of the buffer this free H+ will quickly be removed from solution by binding to the strong base thus decreasing the effect on pH

Front 148

What are three important chemical buffers in the body?

Back 148

bicarbonate

phosphate

protein

Front 149

A buffer would normally maintain the pH around its pKa. The body's normal pH is 7.4 and the pKa of bicarbonate is 6.1. Based on this it does not seem that bicarbonate would make a good buffer yet it does. Why?

Back 149

there is so much of it that even though its pKa is lower the high concentration allows it to maintain the normal body pH of 7.4

Front 150

Proteins are amphoteric. What does this mean?

Back 150

it means that at one end they can act as an acid (give up an H from the carboxy group) and at the other end they can act as a base (accept an H on the amino end)

Front 151

What is the isohydric principle?

Back 151

The chemical buffers in the body are constantly interacting and buffer each other to some degree

Front 152

Ultimately, how does respiration contribute to pH regulation?

Back 152

respiration controls the amount of CO2 present in the body and thus controls the amount of bicarbonate, a major chemical buffer, present

Front 153

What enzyme catalyzes the hydration of CO2 and to form carbonic acid? Where is it found in abundance?

Back 153

carbonic anhydrase

found in RBCs

Front 154

an increase in ventilation would have what effect on body pH?

Back 154

increase pH

increased ventilation would decrease the amount of CO2 present and therefore decrease the amount of carbonic anhydrase available to release H+ ions

Front 155

Decreased body pH will lead to increased ventilation to compensate; however, increased body pH does not lead to a marked decrease in ventilation. Why?

Back 155

a decrease in ventilation cannot be maintained for long periods of time because it will lead to an increase in CO2 concentration and a decrease in O2 concentration. Both of these stimulate an increase in respiration.

Front 156

What effect does increased or decreased blood PCO2 have on bicarbonate reabsorption in the kidneys?

Back 156

increased CO2= increased reabsorption

decreased CO2= decreased reabsorption

more CO2 means more carbonic acid which means more H+. Therefore the kidneys need to save more bicarbonate to buffer it.

Front 157

What are the four possible acid base imbalance conditions?

Back 157

respiratory acidosis

respiratory alkalosis

metabolic (non-respiratory) acidosis

metabolic alkalosis

Front 158

What is the primary cause of respiratory acidosis?

Back 158

increased PCO2

secondarily this leads to increased H+ and bicarbonate

Front 159

What are the compensatory mechanisms for respiratory acidosis?

Back 159

1. chemical buffers

2. increased renal excretion of hydrogen and retention of bicarbonate

Front 160

What are clinical signs of respiratory acidosis

Back 160

dyspnea and cyanosis

Front 161

what is the primary cause of respiratory alkalosis?

Back 161

excessive loss of CO2 due to hyperventilation

Front 162

What are the compensatory mechanisms of respiratory alkalosis

Back 162

- decreased excretion of H+ by the kidneys

- additionally the increase in body pH and fall in PCO2 provide a stimulus to stop hyperventilating

Front 163

Cause of metabolic acidosis

Back 163

abnormal accumulation of fixed acids or loss of a buffer base

Front 164

compensation for metabolic acidosis

Back 164

- increased buffing by bicarbonate--> decreased bicarbonate concentration

- hyperventilation--> decreased CO2

Front 165

Cause of metabolic alkalosis

Back 165

either a loss of hydrogen ions or a marked increase in fixed base (bicarbonate, lactate, citrate)

Front 166

compensation for metabolic alkalosis

Back 166

1. hypoventilation

2. increased secretion of bicarbonate by the kidneys

Front 167

A change in concentration of what molecule indicates some form of respiratory compensation?

Back 167

CO2

< 40 mm Hg= compensation for acidosis

> 40 mm Hg= compensation for alkalosis

Front 168

A change in concentration of what molecule indicates renal compensation for an acid base imbalance?

Back 168

bicarbonate

> 24 mEq/L= compensation for acidosis

<24 mEq/L= compensation for alkalosis

Front 169

What diagnostic information does the anion gap provide?

Back 169

can be used to determine if metabolic acidosis is caused by a loss of bicarbonate or an increase in acid

Front 170

What is an anion gap?

Back 170

it is the difference in the concentration of anions to cations in the body.

under normal conditions these are equal but not all anions can be measured so there is a "normal anion gap"

Front 171

What does an increased anion gap mean? How does it occur?

Back 171

indicates addition of new acid

- when new acid is added bicarbonate buffers it. This reduces the amount of bicarbonate (anion) present thus increasing the gap

Front 172

What does metabolic acidosis with a normal anion gap indicate? What causes it?

Back 172

indicates a loss of bicarbonate

- as bicarbonate (anion) is lost sodium is lost with it.

- the body tries to regain sodium (cation) by reabsorbing it. Chloride (anion) is reabsorbed along with sodium

- this results in decreased bicarbonate (anion), normal sodium (cation) and increased chloride (anion)

- the loss of bicarbonate and gain of chloride balance out resulting in a normal anion gap