LECTURE 11 (Urine formation by the kidneys II) Flashcards

1
Q

What is the equation to calculate Urinary excretion?

A

Urinary excretion = Glomerular filtration - Tubular reabsorption + Tubular secretion

EXPLANATION: urine formation represents the sum of glomerular filtration, tubular reabsorption and tubular secretion

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2
Q

How do we calculate Filtration?

A

Filtration = Glomerular filtration rate X Plasma concentration

[calculation assumes that substance is freely filtered and not bound to plasma proteins]

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3
Q

What differentiates Tubular reabsorption to Glomerular filtration?

A

Tubular reabsorption is is highly selective whereas Glomerular filtration is relatively non-selective

EXPLANATION: Tubular reabsorption reabsorbs glucose + amino acids almost entirely, ions depending on needs of body and waste products in small amounts whereas Glomerular filtration filters everything but Proteins

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4
Q

Describe Tubular reabsorption transport

A

1) Across the tubular epithelial membranes into the renal interstitial fluid
[can be transported through cell membranes themselves “TRANSCELLULAR ROUTE” or through spaces between cell junctions “PARACELLULAR ROUTE”]
2) Through the peritubular capillary membrane back into blood
[transport by “ULTRAFILTRATION” (bulk flow) by hydrostatic and colloid osmotic forces]

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5
Q

Which two ways can solutes be transported across epithelial cells?

A
  • Transcellular pathway = resorbed/secreted across the cells
  • Paracellular pathway = between the cells by moving across tight junctions and intracellular spaces
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6
Q

How is Sodium transported from the tubular lumen back into the blood?

A

1) Na2+ diffuses across the luminal membrane (“apical membrane”) into the cell down an electrochemical gradient established by the Sodium-Potassium ATPase pump on the basolateral side of the membrane
2) Na2+ is transported across the basolateral membrane against an electrochemical gradient by the Sodium-Potassium pump
3) Sodium, water and other substances are reabsorbed into the peritubular capillaries by ULTRAFILTRATION (process driven by hydrostatic and colloid osmotic pressure gradients)

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7
Q

What are the properties of the Sodium-glucose co-transporters (SGLT2 and SGLT1)?

A
  • located on brush border of proximal tubular cells + carry glucose into the cell cytoplasm against a concentration gradient
  • 90% of glucose absorbed by SGLT2 in early part of proximal tubule “S1 segment”
  • 10% transported by SGLT1 in lateral segments of proximal tubules
  • glucose diffuses from cell into interstitial spaces by GLUT2 in S1 segment + GLUT1 in S3 segment of proximal tubule
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8
Q

What happens in glucose reabsorption?

A

Secondary active transport occurs at the luminal membrane -> passive facilitated diffusion occurs at the basolateral membrane -> passive uptake by bulk flow occurs at the peritubular capillaries

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9
Q

What happens in Pinocytosis?

A

Some parts of the proximal tubule reabsorb large molecules (e.g proteins) by PINOCYTOSIS

PROCESS:
1) Protein attaches to brush border of luminal membrane + portion of membrane invaginate to the interior of the cell + completely pinches off and forms vesicle
2) Once inside cell, protein is digested into amino acids which are reabsorbed through basolateral membrane into interstitial fluid

[A form of active transport since requires energy]

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10
Q

What is “Transport maximum”?

A

The limit to the rate at which the solute can be transported

EXPLANATION: The limit is due to saturation of the specific transport systems involved when the amount of solute delivered to the tubule exceeds the capacity of the carrier proteins and specific enzymes involved in the transport process

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11
Q

What is “Gradient-time transport”?

A

The rate of transport that depends on the electrochemical gradient and the time that the substance is in the tubules which depends on tubular flow rate

EXPLANATION: These substances are passively reabsorbed and do not depend on carrier proteins but on electrochemical gradient, permeability of membrane and time of fluid in tubule instead

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12
Q

Describe water reabsorption in the nephron

A
  • When solutes are transported out of the tubule -> concentration decreases inside tubule but increases in renal interstitium -> concentration difference causes osmosis of water in the same direction
  • In proximal tubules = high permeability for water + solutes so move across by tight junctions rapidly
  • Ascending loop of hence = water permeability is low -> no water is reabsorbed despite a large osmotic gradient
  • Distal tubules, collecting tubules, collecting ducts = can be high or low depending on presence or absence of ADH
    [ADH greatly increases water permeability in distal and collecting tubules]
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13
Q

Describe reabsorption of Chloride, Urea and Creatinine

A
  • Active reabsorption of sodium allows PASSIVE reabsorption of chloride by way of an ELECTRICAL POTENTIAL and a CHLORIDE CONCENTRATION GRADIENT
    [transport of +ve Na2+ leaves lumen -ve charged compared to interstitial fluid -> ions diffuse passively through paracellular pathway; reabsorption of water increases concentration in lumen allowing for Cl- diffusion into interstitial fluid]
  • Urea is passively reabsorbed from tubule (in the same mechanism as Cl- with water) but to a lesser extent since it needs UREA TRANSPORTERS
  • Almost NONE of creatinine is reabsorbed since is impermeable to tubular membrane
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14
Q

How is the proximal tubule adapted to reabsorb large amounts of water and solutes?

A
  • Highly metabolic + have large numbers of mitochondria to support powerful active transport processes
  • Extensive brush border on luminal side of membrane + labyrinth of intercellular and basal channels -> extensive surface area for rapid transport
  • Protein carrier molecules -> transports large amount of Na2+
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15
Q

What is the difference between the first and second half of the proximal tubule?

A
  • First half = sodium is reabsorbed by co-transport with glucose, amino acids and other solutes
  • Second half = sodium is reabsorbed with CHLORIDE ions
    [when glucose and other solutes are reabsorbed it leaves chloride to have a higher concentration -> favours diffusion from lumen into renal interstitial fluid]
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16
Q

What are the different concentrations of solutes along the proximal tubule?

A
  • Amount of Na2+ decreases but CONCENTRATION is constant since water reabsorption keeps pace with Na2+ reabsorption
  • Organic solutes (e.g glucose) are highly reabsorbed -> decrease along length of proximal tubule
  • Creatinine concentration increases since is not reabsorbed
17
Q

What does the Loop of Henle consist of?

A
  • Thin descending segment
  • Thin ascending segment
  • Thick ascending segment
18
Q

Describe the different segments of the Loop of henle

A
  • Thin ascending + descending parts have thin epithelial membranes with no brush border and few mitochondria -> allows simple diffusion through its walls
  • Thin descending limb -> water reabsorption
  • Thick and thin ascending limbs -> virtually impermeable to water [tubular fluid delivered to distal tubule is dilute]
  • Thick ascending limb has a 1-SODIUM, 2-CHLORIDE, 1-POTASSIUM CO-TRANSPORTER and a SODIUM-POTASSIUM ATPase pump
    [backleak of K+ back into lumen creates a +ve charge which forces Mg2+ and Ca2+ from lumen into interstitial fluid]
19
Q

What happens in the Distal tubule?

A
  • First portion forms “macula densa” which provides feedback control of GFR and blood flow
  • Reabsorbs most ions but is impermeable to water and urea -> “diluting segment”
  • Sodium-chloride co-transporter moves NaCl from tubular lumen into cell and Sodium-potassium ATPase pump transport sodium out of the cell across the basolateral membrane [hypertension drugs inhibit sodium-chloride transporter]
20
Q

What are Principal cells and Intercalated cells?

A

Both cells are found in the second half of the distal tubule and collecting tubule

  • Principal cells = reabsorb sodium and water from the lumen + secrete potassium ions into the lumen
  • Intercalated cells = reabsorb potassium ions and secrete hydrogen ions into the lumen
21
Q

How does secretion of Potassium from blood into lumen happen?

A

1) Potassium enters the cell though the Sodium-Potassium ATPase pump -> maintains a high intracellular potassium concentration
2) Once in cell, potassium diffuses down its concentration gradient across the luminal membrane into the tubular fluid

22
Q

Summarise the function of the late distal tubule and cortical collecting tubule

A
  • Almost completely impermeable to urea (some reabsorption occurs in medullary collecting ducts)
  • Reabsorb Na2+ ans secrete K+ from peritubular capillary blood into the tubular lumen (process controlled by aldosterone)
  • Secrete H+ by Hydrogen-ATPase against a large concentration gradient
  • Permeability of water is controlled by ADH/Vasopressin
23
Q

What is the Medullary collecting duct?

A

The final site of urine processing and plays an important role in determining the final urine output of water and solutes

CHARACTERISTICS:
- cuboidal in shape with smooth surfaces and few mitochondria
- Permeability is controlled by ADH
- Permeable to urea with “urea transporters” -> helps raise osmolality allowing formation of concentrated urine
- Can secrete H+ ions against a large concentration gradient

24
Q

What is Glomerulotubular balance?

A

The intrinsic ability of the tubules to increase their reabsorption rate in response to increased tubular flow (as GFR increases, reabsorption increases -> prevents overloading of distal tubular segments when GFR increases)

25
Q

How do you calculate Reabsorption across the peritubular capillaries?

A

Reabsorption = Kf X Net reabsorptive force

Net reabsorptive force is the sum of hydrostatic and colloid osmotic forces
- Peritubular hydrostatic pressure -> opposes reabsorption
- Renal interstitium hydrostatic pressure -> favours reabsorption
- Peritubular osmotic pressure -> favours reabsorption
- Renal interstitium osmotic pressure -> opposes reabsorption

26
Q

What determines Peritubular capillary reabsorption?

A

Hydrostatic and colloid osmotic pressures

Peritubular capillary hydrostatic pressure is influenced by arterial pressure and resistance of afferent and efferent arterioles
- Increase in arterial pressure increase hydrostatic pressure + decrease reabsorption rate
- Increase in resistance of afferent and efferent arterioles reduces hydrostatic pressure + increases reabsorption rate
[constriction of efferent arterioles increases glomerular capillary hydrostatic pressure but lowers peritubular capillary hydrostatic pressure]

Colloid osmotic pressure is determined by systemic plasma colloid osmotic pressure and filtration fraction
- Increasing plasma protein concentration increases capillary colloid osmotic pressure + increases reabsorption
- The higher the filtration fraction, the greater fraction of plasma filtered through glomerulus, the more concentrated protein in plasma remains -> increases capillary reabsorption rate

27
Q

What are the effects of increased renal arterial pressure?

A
  • Increased GFR
  • Decreases the % of the filtered load of sodium and water that is reabsorbed by the tubules (increases peritubular capillary hydrostatic pressure) -> increases urine output
  • Reduced angiotensin II formation
    [increases sodium reabsorption + stimulates aldosterone secretion which increases sodium reabsorption]
28
Q

Describe Aldosterone

A

SITE OF ACTION: Collecting tubule and duct
EFFECTS: NaCl and H2O reabsorption + K+ secretion

MECHANISM:
- stimulates Sodium-potassium ATPase pump on basolateral side of cortical collecting tubule membrane
- increases sodium permeability of the luminal side of membrane

STIMULI FOR SECRETION:
- increased extracellular potassium concentration
- increased angiotensin II levels (occur with sodium and volume depletion/low blood pressure)

DISEASES:
- Addison’s disease (absence of aldosterone due to adrenal destruction/malfunction) -> loss of Na2+ and accumulation of K+
- Conn’s syndrome (adrenal tumour) -> sodium retention + decreased plasma K+ concentration

29
Q

Describe Angiotensin II

A

SITE OF ACTION: Proximal tubule, thick ascending loop of Henle/distal tubule, collecting tubule
EFFECTS: NaCl and H2O reabsorption + H+ secretion

MECHANISM:
- Stimulates aldosterone secretion (increases sodium reabsorption)
- Constricts efferent arterioles
[reduces peritubular capillary hydrostatic pressure which increases reabsorption + reduces blood flow which increases filtration fraction in glomerulus which increases colloid osmotic pressure, raising reabsorption]
- Directly stimulates sodium reabsorption in proximal tubules, loop of Henle, distal tubules and collecting tubules

STIMULATION FOR SECRETION:
- Low blood pressure and/or low ECF (during haemorrhage, excessive sweating, diarrhoea)

30
Q

Describe ADH (Antidiuretic hormone)

A

SITE OF ACTION: Distal tubule/collecting tubule and duct
EFFECTS: Increase H2O reabsorption

MECHANISM:
- In absence of ADH, permeability to water is low so kidneys excrete large amounts of dilute urine
- ADH binds to specific V2 receptors in late distal tubules, collecting tubules and ducts, increasing the formation of cyclic AMP + activates protein kinases -> stimulates movement of intracellular protein “AQP-2” to luminal side of membrane -> molecules of AQP-2 cluster together + fuse with cell membrane by EXOCYTOSIS to form WATER CHANNELS that allow for rapid diffusion of water

31
Q

Describe Atrial Natriuretic peptide

A

SITE OF ACTION: Distal tubule/collecting tubule and duct
EFFECTS: Decreased NaCl reabsorption

MECHANISM:
- Inhibit reabsorption of sodium and water
- Inhibits renin secretion, preventing angiotensin II formation (reduces sodium reabsorption) -> increases urinary excretion, returning blood volume back to normal

DISEASES:
- ANP level elevated in CONGESTIVE HEART FAILURE when cardiac atria are stretched due to impaired pumping of ventricles

32
Q

Describe Parathyroid hormone

A

SITE OF ACTION: Proximal tubule + thick ascending loop of Henle/distal tubule
EFFECTS: Decreased phosphate reabsorption + Increased Calcium reabsorption

33
Q

What are the effects of the sympathetic nervous system on sodium reabsorption?

A
  • Decreases Na2+ and H2O excretion by contracting the renal arterioles, reducing GFR
  • Increases renin release and angiotensin II formation -> increases tubular reabsorption and decreases renal excretion of sodium
34
Q

What is Renal clearance?

A

Renal clearance of a substance is the volume of plasma that is completely cleared of the substance by the kidneys per unit time

Cs = Us X V / Ps

Us - urine concentration
V - urine flow rate
[Us X V is “urinary excretion rate”]
Ps - plasma concentration

35
Q

What is Inulin?

A

A polysaccharide that is not produced in the body and is administered to patients to measure GFR

36
Q

Why can creatinine be used to mature GFR?

A

Despite it being a by-product of muscle metabolic, it is cleared from the body almost entirely by glomerular filtration

37
Q

How can you calculate Total renal plasma flow?

A

Total renal plasma flow = PAH clearance/ PAH extraction ratio

[Extraction ratio is renal arterial PAH minus renal venous PAH decided by renal arterial PAH concentration]

38
Q

Describe the comparisons of Inulin clearance with clearances of different solutes

A
  • Clearance rate EQUALS inulin = substance is only filtered and not reabsorbed or secreted
  • Clearance rate LESS than inulin = substance reabsorbed by nephron tubules
  • Clearance rate GREATER than inulin = substance secreted by nephron tubules