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STEP Physiology > Proximal Tubule > Flashcards

Proximal Tubule Flashcards

1
Q

T or F. The kidney excretes metabolic waste products such as urea, creatinine and uric acid as fast as they are produced in the body assuming a normally functioning kidney

A

T, so that their level in body fluid is at a very low, non-toxic level.

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2
Q

How many times is plasma filtered through the glomerulus?

A

The entire plasma is filtered through glomerulus about 60 times every day that is equivalent to filtration of entire body fluid about 5 times a day. Such high rate of filtration enables the body to get rid of the waste products as fast as they produced in the body.

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3
Q

How much of the GF is reabsorbed in the PT?

A

about 2/3. So, the primary role of PT is to reabsorb most of the water and solutes filtered into glomerulus.

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4
Q

What is the main function of the distal tubule?

A

On the other hand the function of distal tubule is regulation of water and solute absorption/secretion and determine the urine composition to suite the physiological status of body fluid volume and composition.

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5
Q

What does the epithelium of the proximal tubule look like apically? Why?

A

In the luminal side the plasma membrane of epithelial cells is folded into many finger like projections called microvilli. This increases the surface area of apical membrane by thousands of folds, which is much needed for the massive reabsorption of glomerular filtrate in the proximal tubule.

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6
Q

T or F. The reabsorption in the PT is iso-osmotic.

A

T.

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7
Q

Why is the PT also an important regulatory site in controlling ECF?

A

Due to the volume of fluid absorbed in the PT, any change in the rate of reabsorption here can have significant impact on the volume of ECF.

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8
Q

What is the normal rate of plasma filtration through a glomerulus? Reabsorption in the PT?

A

130ml/min85ml/minTherefore, GF is delivered into the LOH at the rate of 45 ml/min

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9
Q

T or F. Reabsorption in PT is iso-osmotic, that means there is virtually no change in osmolarity of GF as it flows along the PT.

A

T.

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10
Q

How can we determine the fluid amount rate absorbed in the PT?

A

Can determine by tracking the concentration of a substance that is not reabsorbed in the PT nor it is secreted by the tubular epithelial cells, namely inulin So, if you infuse inulin intravenously to maintain a plasma concentration of 1 mg/dl, and measure inulin concentration in the tubular fluid, you can calculate the rate of water absorption in the PT. You can use a glass micropipette to withdraw TF from the PT. Eqn on next slide

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11
Q

What is the mass flow balance in the PT for inulin?

A

GFR - reabsorption = the volume of GF delivered into the LOH. So, GFR times plasma inulin concentration is equal to V-L, that is the rate of flow into LOH, x the inulin concentration in the TF. Rate of flow into LOH or V-L therefore is GFR x plasma inulin concentration (Pin) divided by inulin concentration in the TF. According to the numbers we have it is 130 times 1 divided by 3; that is 43 ml/min delivered into LOH. So, 130-43 is 87 ml/min, what is reabsorbed in the PT, that is 2/3rd of GFR.

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12
Q

Describe the relationship between the TF to plasma inulin concentration ratio (x) at different distance from the glomerulus (y) in the PT.

A

Linearly increasing, indicating that fluid is absorbed through out the length of PT making the inulin more concentrated.

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13
Q

T or F. Even though inulin concentration is increased along the length of PT, the osmolarity of TF remains virtually the same from the glomerular end to the loop end.

A

T. Because the absorption is iso-osmotic in the PT

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14
Q

What is the mass flow of solutes into the PT normally? Mass flow of reabsorption in the PT?

A

The plasma osmolarity is about 290 mOmol/L and the GFR is 130 ml/min, and therefore the flow of solutes in PT is 37.7 mOsmol/min. Reabsorption is 2/3rd of GFR which is 86.6 ml/min, and at isoosmolar reabsorption condition, the solute reabsoprtion is 25.1 mOsmol/min (0.290*86.6). This means that solute is delivered to LOH at the rate of 12.6 mOsmol/min.The major solutes that contribute to isoosmotic reabsorption from the PT are sodium, chloride and bicarbonate

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15
Q

Where does Na+ absorption primarily occur?

A

Sodium reabsorption occurs throughout the tubule, although 65% of it is reabsorbed in the PT.

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16
Q

How is Na+ reabsorbed?

A

It is reabsorbed by an active transport mechanism, and the same mechanism is used throughout the tubule. Due to the involvement of active transport mechanism it is an energy consuming process and accounts for majority of the oxygen consumed in the kidney.

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17
Q

Describe the wall of the PT.

A

The luminal surface of the wall of PT is lined with the epithelium, monolayer of polarized epithelial cells.At the apical end of epithelial cells the intercellular space is sealed by a selectively permeable junctional complex called a tight junction.

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18
Q

What are the tight junctions made from?

A

made up of complex of proteins providing a barrier function, which means it allows diffusion of selective molecules based on size and charge, while preventing diffusion of most molecules. It has pore pathways that allows diffusion of specific ions (claudins) and leak pathways that allows diffusion of molecules based on size. But, most ions and solutes have to be absorbed by a transcellular route.

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19
Q

T or F. The major portion of Sodium is absorbed by transcellular pathways

A

T.

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20
Q

Describe transcellular reabsorption.

A

On the luminal membrane there are Na+ channels that allow free diffusion of Na+ from the lumen to the cytoplasm. The channels for Na absorption in the luminal membrane are several – NHE, Na-Glucose, Na-amino acid and Na-PO4 cotransporters

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21
Q

What is the main driving force for NA absorption?

A

The NKA pump. It is located in the basolateral membrane and transports 3 Na out of the cell and 2 K into the cell at the expense of one molecule of ATP.

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22
Q

What are the results of NKA activity?

A

The decrease in intracellular Na+ concentration and reduction of membrane potential to almost -70 mV. Both reduction of Na conc. in the cytoplasm and negative membrane potential are poised to drive Na reabsorption from the TF into the cytoplasm. The potential energy of downhill movement of sodium at the luminal membrane is used in the transport of solutes such as glucose and amino acids.

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23
Q

Sodium reabsorption in the proximal tubule is accompanied by what?

A

The absorption of equivalent amounts of anions to maintain electro neutrality.

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24
Q

What happens to the TF as sodium is reabsorbed?

A

As the sodium is reabsorbed by an active transport process, the TF becomes more and more negative. It can be 5 mV more negative than the interstitial fluid. This lumen negative electrical potential drives the transport of chloride and bicarbonate from the TF into the interstitial fluid.

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25
Q

How is Cl transported in the PT?

A

paracellular routes. Cldn 4 in the tight junction forms chloride selective pores.The majority of chloride is absorbed via paracellular route. But, there could be small portion transported by active transport mechanism via anion exchangers.

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26
Q

How does HCO3- reabsorption occur?

A

Bicarbonate transport is coupled to NHE, this is an active transport process. Therefore, more HCO3 is reabsorbed in the proximal part of proximal tubule compared to chloride reabsorption.

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27
Q

T or F. Bicarbonate reabsorption is prefered over Cl in the PT.

A

T. Unlike Cl transport, which is a passive diffusion, bicarbonate transport is active and driven by proton secretion.

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28
Q

Where all does HCO3- reabsorption occur?

A

Bicarbonate absorption occurs in the PT, DT and CD of nephron, and it is coupled to proton secretion into the lumen.

29
Q

What is the difference between the HCO3- reabsorption in the PT, DT and CD?

A

the mechanism involved in proton secretion. NOTE: In all segments the intracellular enzyme carbonic anhydrase catalyzes formation of carbonic acid from carbon dioxide and water. Carbonic acid under physiologic pH dissociates into proton and bicarbonate. Proton is secreted into lumen, while bicarbonate is transported into interstitial fluid.

30
Q

How is proton secretion mediated in the PT?

A

In the PT, proton secretion is mediated by the luminal membrane channel called NHE, which is an antiporter.One hydrogen ion is secreted out when one Na is transpotted into the cell.

31
Q

What does the secreted H ion do once in the TF?

A

Secreted H ion combines with the bicarbonate in TF to form carbonic acid.

32
Q

What happens to the carbonic acid?

A

A membrane bound carbonic anhydrase enzyme in the luminal membrane breaks carbonic acid into carbon dioxide and water. Carbon dioxide freely diffuse into cell and across the cell into interstitial fluid. The bicarbonate formed during the production of proton by intracellular CA is actively transported across the BL membrane into interstitial fluid by a Na/bicarboate co-transporter.

33
Q

Due to the active transport process, most of bicarbonate is reabsorbed from the PT.

A

The filtered HCO3 conc is 25 mml/L. HCO3 conc in TF is 3.8 mmol/L. So the mass flow of HCO filtered into PT is 3.25 mmol/min [(130mL/min)(0.025 mmol/ml)] and mass flow of HCO from PT to LOH is 0.17 mmol/min [(44 mL/min)(0.0038 mol/min)]. Therefore, 95% of HCO is reabsorbed in the PT.

34
Q

It is not just a neutralization of HCO3. The luminal HCO3 is neutralized by the proton secreted by the cells. However, a HCO3 is formed inside the cell during proton production by CA.

A

This HCO is transported into IF. So, there is a net absorption of one molecule of HCO for each HCO neutralized in the lumen. Net result is HCO absorption.This is an active transport mechanism coupled to active transport of Na.

35
Q

How is the water absorbed from the PT?

A

Water absorption is driven by osmotic gradient. The massive solute transport of Na+ reabsorption followed by passive diffusion of anions results in a drop in the osmolarity of TF and an increase in omsolarity in the interstitial fluid.

36
Q

What ways does water cross the epithelium out of the lumen?

A

Water transport occurs by both paracellular route in so called leaky epithelium andby transcellular pathway via the water channels called aquaporins on the luminal membrane and basolateral membrane.

37
Q

What are the forms of aquaporins?

A

AQ-1 is at the luminal membrane, AQ-4/5 are in the basolateral membrane.AQ-2 is in DT, regulated by ADH or vasopressin.

38
Q

Once the fluid with salts is absorbed across the epithelium from the lumen of PT, how is it absorbed into the peritubular capillary?

A

Three different starling forces are involved in this process:1) Positive interstitial fluid pressure. 2) Low hydrostatic pressure in the peritubular capillary 3) High oncotic pressure in peritubular capillary

39
Q

How does positive interstitial fluid pressure promote capillary uptake of fluid from the interstitial field?

A

You have higher hydrostatic pressure in the interstitial space due to fluid accumulation. That favors fluid uptake into the capillary.

40
Q

How does Low hydrostatic pressure in the peritubular capillary promote capillary uptake of fluid from the interstitial field?

A

As a portion of plasma is filtered through glomerular capillary bed the volume of blood delivered to peritubular capillary is about 20% lower than that in the afferent arteriole. This favors fluid uptake.

41
Q

How does high oncotic pressure in peritubular capillary promote capillary uptake of fluid from the interstitial field?

A

Due to ultra filtration of plasma in the glomerular capillary the protein conc. in the peritubular capillary is increased resulting in increased oncotic pressure. This also favors fluid uptake by the capillary.

42
Q

T or F. Fluid reabsorption from the PT is iso-osmotic. However, the solute absorption in the PT is selective, not all solutes are absorbed at the same rate. Some are absorbed faster than others and some are not absorbed at all.

A

T. If you can measure the concentration of each solute in the TF at different lengths of PT you can have some idea about their transport properties

43
Q

Why is the absorption of Na and Cl isoosmotic?

A

Their concentrations do not change along the length of PT because water absorption is the result of osmotic gradient created by NaCl reabsorption. NOTE: There is a slight increase in Cl concentration at the end of the PT; this is due to a more dominant absorption of HCO3 in the convoluted PT (HCO3- is slightly dilute).

44
Q

Why is HCO3 absorbed faster than Cl-?

A

This is because Cl absorption occurs by passive diffusion, whereas bicarbonate absorption involves active transport mechanism

45
Q

How does the concentration of glucose, AA, and organic acids change along the length of the PT?

A

Glucose, aa and organic acids need to be conserved and are completely reabsorbed by the nephron. They are absorbed by active transport mechanisms and therefore, their conc in the TF are reduced gradually along the length of PT.

46
Q

How does the concentration of inulin or PAH change along the length of the PT?

A

Inulin is not an endogenous solute. But, if you infuse inulin intravenously and measure its concentration in TF along the length of PT you will find that the concentration increases along PTthis is because inulin is not reabsorbed.Unlike inulin PAH is actively secreted by PT, and therefore its concetration in the TF is much higher than inulin.

47
Q

How is glucose reabsorption in the PT controlled?

A

the Na-Glu co-transporter in the luminal membrane of the epithelial cells, which allows transport of one molecule of glucose along with one equivalent of Na from the TF into the cytoplasm. Two isoforms of glucose transporter are SGLT1 and SGLT2. So, glucose transport is coupled to Na electrochemical gradient, and therefore it is an active transport mechanism. This active transport is essential as all of glucose in GF needs to be reabsorbed in the PT.

48
Q

Can any amount of glucose be reabsorbed?

A

No, glucose is only completely reabsorbed until it reaches a threshold level of plasma glucose which is 200-220 mg/dl (aka threshold).

49
Q

Describe the relationship of glomerular filtration of glucose with plasma glucose level (x)

A

glomerular filtration of glucose is increased linearly with the increase in plasma glucose level. 100% of filtered glucose is reabsorbed until a certain concentration of plasma glucose. Until this conc., rate of filtration is equal to rate of reabsorption,

50
Q

Why at a certain conc does the reabsorption of glucose decrease from 100%?

A

because some of the glucose transporter molecules gets saturated.so unabsorbed glucose is excreted in urine.

51
Q

As the filtered glucose level is increased above the threshold more and more glucose transporters are saturated and finally reach a state when all transporters are occupied, and the rate reabsorption remains constant. Any further increase in glucose in the filtrate would be excreted out in the urine. Not all nephrons have same capacity. So, at threshold some nephrons are saturated and begin to excrete glucose in urine. With further increase in glucose all nephrons are saturated. This concentration is called what?

A

transport maximum, which is either 375 mg/min or 350 mg/dlTm is reduced in chronic renal failure due to reduced number of functional nephrons.

52
Q

What are physiological causes of glucosuria? Pathologic?

A

pregnancy, and pathophysiologic causes are diabetes mellitus and mutation in SGLT1 and SGLT2, a condition known as familial renal glucosuria.

53
Q

How are AAs reabsorbed from the PT?

A

coupled to Na electrochemical gradient via Na-amino acid co-transporters

54
Q

Are all AAs transported by the same transporters?

A

No, There are several isoforms of Na-amino acid cotransporters, some are specific for neutral amino acids, whereas others specific for either acidic or basic amino acids. Similar to glucose, almost all amino acids are reabsorbed from the PT.

55
Q

How are metabolic intermediates reabsorbed from the PT?

A

Also coupled to Na electrochemical gradient.

56
Q

Is the plasma conc of metabolic intermediates normally low or high?

A

Normally, the concentration of metabolic intermediates in the plasma is low. But, it can be high under pathophysiologic conditions, such as diabetes mellitus. In such conditions, the plasma concentration of metabolites may exceed the capacity of PT to reabsorb, and therefore a part of it may be excreted in the urine. Diabetic ketosuria is example of that.

57
Q

T or F. Normally, protein in the GF is low, but peptides are filtered through the glomerulus.

A

PT epithelial cells have peptide transporters that can reabsorb the filtered peptides.

58
Q

When could protein appear in the GF?

A

Protein may appear in GF in conditions such as multiple sclerosis, hemoglobinemia or myoglobinemia. Since these proteins cannot be reabsorbed, they will be excrete in the urine

59
Q

How are phosphates reabsorbed from the PT?

A

Also coupled to Na electrochemical gradient and therefore uses the potential energy associated with the downhill transport of Na. Therefore, it is an active transport mechanism.

60
Q

T or F. Phosphate reabsorption has low threshold

A

T, and hence phosphate is partially excreted in the urine. Threshold is normally poised to match the physiological concentration of phosphate in the plasma. Therefore, any excess of phosphate in daily intake is excreted oiut in the urine

61
Q

What regulates transport maximum for phosphate?

A

hormones. For example PTH, the parathyroid hormone, decreases Tm for phosphate and therefore facilitates phosphate excretion in the urine

62
Q

How is Cl- reabsorbed from the PT?

A

Cl is reabsorbed by passive diffusion across the renal tubular epithelium.

63
Q

What are driving forces of Cl-reabsorption?

A

-concentration gradient created by water reabsorption, -electrochemical gradient created by Na reabsorption.While 66% of fluid is reabsorbed in the PT, only 60% of Cl is reabsorbed due to competition by HCO, which is reabsorbed by an active transport mechanism.

64
Q

How is K+ reabsorbed from the PT?

A

Reabsorption of potassium also occurs by passive transport mechanism. Predominantly, it is transported via tight junctions. Some of the claudins in the tight junctions form cation selective pores.

65
Q

How is urea reabsorbed from the PT? Is it effective?

A

The passive transport of urea is relatively slow and only 50% of filtered urea is reabsorbed, therefore 50% of filtered urea is excreted in the urine. Urea clearance in urine can be increased by increasing the urinary flow.

66
Q

Substances that are freely filtered through glomerulus, but not reabsorbed can cause what?

A

Increase the TF osmolarity and cause diuresis, that is excessive water excretion in the urine. Such substances have clinical significance to stimulate diuresis and reduce ECFV. Examples of such conditions are intracranial and intra ocular pressure and edema. It is also indicated to promote excretion of toxins form the body.

67
Q

What is Mannitol?

A

an inert monosaccharide, not produced in the body nor degraded in the body. It is water soluble, freely filtered into GF, not reabsorbed nor secreted in the PT and is typically used in the clinic to induce diuresis

68
Q

If you continuously infuse mannitol at concentration of 30 mml/L the plasma osmolarity will be increased by 30 mOsm/l, so the total plasma osmoloarity will be 320 mOsm/L instead of 290 mOml/L.

A

Mannitol filtered into GF would be 3.9 mO,/min, when GFR is 130 ml/min. Under such conditions, the delivery of manntiol to LOH was 67.8 mMol/L. Theoretically, if the water rabsorption was unaffected the mannitol should be delivered to LOH at a concentration of 90 mMol/L. This suggests that there was a reduction in fluid reabsorption in the PT equivalent to the amount of mannitol in the TF.

69
Q

What are some examples of substances that are secreted into the PT?

A

-organic acids and bases, -creatinine, -PAH or paraamino hippuric acid and others. Mostly this process occurs by active transport mechanisms. Na co-transporters and other co-transporters are involved in tubular secretion of substances.

STEP Physiology (68 decks)

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