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Theme 3: The Excretory System and Renal Function > Formation of urine 1 > Flashcards

Formation of urine 1 Flashcards

1
Q

5 major stages of urine formation

A

1: glomerulus: filtration of blood
2: proximal tubule: reabsorption of filtrate, secretion into tubule
3: loop of henle: concentration of urine
4: distal tubule: modification of urine
5: collecting duct: final modification of urine

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2
Q

Three major functions of the nephron

A

Filtration of blood to produce a filtrate

Reabsorption of water, ions and organic nutrients from filtrate

Secretion of waste products into tubular fluid

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3
Q

Basal renal processes: filtration

A

Force for filtration is:

  • blood pressure
  • differing diameter of afferent and efferent arterioles
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4
Q

Glomerular filtration rate

A

=125mL/min (180L/day)

Rate at which glomerular filtrate is produced

GFR can be measured clinically and used as an indicator of renal function

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5
Q

Ultrafiltration

A

Filtration on a molecular scale

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6
Q

Glomerular filtration

A

All small molecules are filtered

  • electrolytes
  • amino acids
  • glucose
  • metabolic waste
  • some drugs, metabolites

Cells and large molecules remain in the blood

  • red blood cells
  • lipids
  • proteins
  • most drugs, metabolites
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7
Q

Pathway filtrate must go through

A

1: Pores in glomerular capillary epithelium
2: The basement membrane of Bowman’s capsule (includes contractile mesangial cells)
3: Epithelial cells of Bowman’s capsule (podocytes) via filtration slits into capsular space

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8
Q

Filtration pressure equation

A

(PGC)-(PBS+PiGC)

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9
Q

PGC

A

Pressure within glomerular capillary

Hydrostatic pressure=45mmHg

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10
Q

Plasma protein pressure

A

Osmotic pressure=25mmHg

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11
Q

PBC

A

Pressure within Bowman’s capsule

Hydrostatic pressure=10mmHg

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12
Q

Autoregulation of renal blood flow

A

Subject to autoregulation over broad range of systemic BPs (90-200mmHg)

Persists in denervated kidneys so it is not a neuronal or hormonal response but a local effect

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13
Q

Two hypothesis for autoregulation of renal blood flow

A

Myogenic- autoregulation is ue to response of renal arterioles to stretch

Metabolic- renal metabolites modulate vasodilation

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14
Q

Changes in GFR can also alter systemic blood pressure

A
  1. Drop in filtration pressure caused drop in GFR
  2. Lower GFR means less Na+ enters the proximal tubule
  3. The macula densa senses a change in tubular Na+ levels
  4. This stimulates juxtaglomerular cells to release renin into the blood
  5. Renin release leads to generation of angiotensin II
  6. Ang II is a vasoconstrictor which causes BP to increase
  7. Increased BP causes filtration pressure to increase and GFR returns to normal
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15
Q

Renin-angiotensin system

A

Homeostasis disturbed (decreased GFR)

Renin release

Angiotensin activation

Elevation of blood pressure and blood volume

Homeostasis restored (increased GFR)

Homeostasis

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16
Q

Reabsorption from the proximal tubule

A

Glomerular filtrate enters the proximal tubule where
- 60-70% filtered water, Na+, HCO3-, Cl-, K+ and urea are reabsorbed from PT

Almost complete reabsorption of

  • glucose
  • amino acids
  • small amount of filtered proteins
17
Q

Na+/K+/ATPase drives reabsorption

A

Na+/K+/ATPase pumps out Na+ from cells into blood against chemical and electrical gradients

Process requires energy in the form of adenosine triphosphate

Accompanied by entry of K+ ions which rapidly diffuses out of cell

Ratio of transport is 3 Na+ leaving cell: 2 K+ entering cell

18
Q

Na+ reabsorption from the PT

A

PT cells have low intracellular Na+ concentration due to the action of the Na+/K+/ATPase

PT cells have overall negative charge due to the presence of intracellular proteins

19
Q

Water reabsorption from the PT

A

60-70% filtered water reabsorbed in PT- active transport of Na+ out of PT is driving force

Movement of solutes reduces osmolality of tubular fluid and increases osmolality of interstitial fluid

Net flow of water from tubule lumen to lateral spaces occurs by transcellular and paracellular routes

Transcellular routes involve aqauporin channels on apical and basolateral surfaces

No active water reabsorption along nephron- occurs by osmosis and follows sodium

PT highly permeable to water

20
Q

Aquaporin 1

A

Abundant distribution in proximal tubule

Wide distribution

21
Q

Aquaporin 2

A

Present in collecting duct on apical surface

Expression controlled by ADH

22
Q

Aquaporin 3 and 4

A

Present on basolateral surface of collecting duct cells

23
Q

Glucose reabsorption from the PT

A

Glucose is co-transported into the PT cell with sodium

Glucose is co-transported into the PT cell with sodium very efficiently so very little is excreted

24
Q

SGLT2 inhibitors

New drug for controlling type 2 diabetes?

A

Idea is to make diabetic patients excrete more glucose leading to an overall hypoglycaemic effect

25
Q

Further reabsorption in the PT

A

Potassium
- 70% of filtered K+ reabsorbed in PT, mostly passively via tight junctions

Urea
- 40-50% filtered urea is reabsorbed passively in the PT down its concentration gradient

Amino acids

  • 7 independent transport processes for reabsorption of AAs from the PT (depends on type of aa)
  • high Tm for transport so that as much as possible is reabsorbed from PT

Proteins
- reabsorbed from the PT via receptor mediated endocytosis

26
Q

Protein reabsorption from the PT

A

Small amounts of protein pass into filtrate via the glomerulus

They are reabsorbed by pinocytosis

Vesicles transported into cell, degraded by lysosomes and amino acids returned to blood

Only limited transport capacity

Proteinuria is a sign of glomerular damage and impending renal failure

27
Q

Secretion into the PT

A

Some endogenous substances and drugs cannot be filtered at glomerulus (size or protein binding)

Specialised pumps in PT can transport compounds from the plasma into the nephron

Two kinds of pumps

  • for organic acids
  • for organic bases
28
Q

OAT

A

Organic anion transporter

29
Q

MRP

A

Multi-drug resistant protein

30
Q

a-KG

A

a-ketoglutarate

31
Q

Secretion of PAH into the PT

A

PAH secreted into PT from blood

Not an endogenous compound so can be used as a tool to measure tubular secretion

Transported into PT cells from blood with a-ketoglutarate or other di/tri carboxylases

Transported out of PT cells in exchange for another anion present in the PT lumen

32
Q

PAH

A

Para-amino hippurate

33
Q

Organic endogenous acids secreted into urine by the PT

A

cAMP

Bile salts

Hippurates

Oxalate

Prostaglandins

Urate

34
Q

Organic acids drugs secreted into urine by the PT

A

Acetozolamide

Chlorothiazide

Furosemide

Penicillin

Probencid

Salicylate

Hydrochlorothiazide

Bumetanide

35
Q

Some organic endogenous bases secreted into urine by the PT

A

Creatinine

Dopamine

Adrenaline

Noradrenaline

Histamine

Choline

Thiamine, guanidine

36
Q

Some organic base drugs secreted into urine by the PT

A

Atropine

Isoproterenol

Cimetidine

Morphine

Quinine

Amiloride

Procainamide

Theme 3: The Excretory System and Renal Function (13 decks)

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