0804- Glomerular filtration and its determinants- CG Flashcards

1
Q

At the end of this lecture students should be able to • outline the physiologically relevant parts of renal anatomy; • discuss the significance of the micropuncture technique in studying renal function; • explain what makes up the filter and its properties; • demonstrate why and how the following factors determine filtration: PCap, PInterst and πColosm; • identify mechanisms involved in constancy of perfusion (autoregulation); • discuss how GFR can be regulated independent of RBF; and • recognise VSMC mechanisms resulting in renal vasomotion.

A

yes indeed

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2
Q

Outline the physiologically relevant parts of renal anatomy;

A

Afferent arteriole, efferent arteriole, glomerulus + bowman’s capsule Filtration driven by blood perfusion in capillaries (RBF and FF) Regulation of pressure, filtration

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3
Q

• discuss the significance of the micropuncture technique in studying renal function;

A

Detach/separate what happens before and after the oil drop, can investigate exactly what’s going on

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4
Q

• explain what makes up the filter and its properties. What tends to get filtered?

A

Ultrafilter- A semipermeable membrane used as a filter to separate colloids and large molecules from water and small molecules, which pass through =Plasma is filtered (NO CELLS): result is an ultrafiltrate. 3 filter Elements - endothelial fenestrations (between cells) - matrix of basal membrane (collagen + proteins) - podocyte (fine filter- polysaccharide, macromolecule filter) MW>69kda (albumin), negative charged less filterable positively charged- retention

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5
Q

• demonstrate why and how the following factors determine filtration: PCap, PInterst and πColosm;

A

PCap = filtration force, produced by LV πColosm= pressure caused by protein etc in plasma, not filtered but osmotically active (ie albumin)- also resistive to filtration PInterst= Bowman’s capsule fluid pressure (resistive pressure to be overcome) Peff is PCap - (other 2 properties) Only πColosm changes along capillary length (increases as water is filtered away) Reserve, created by long capillaries- High plasma flow –> require filtration over longer capillaries

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6
Q

• identify mechanisms involved in constancy of perfusion (autoregulation); Purpose- keep urine concentration between a certain range, reduce need for capillary length reserve..

A

Autoregulation of RBF ensure constancy of plasma flow, filtration rate, filtration fraction (FF), and excretion (just like autoregulation of arterioles ensure constant blood flow in other regions) Range is only between 80-180mmHg (above that GFR is independent of RBF) If perfusion pressure (ΔP) increases, resistance (RKidney) needs to rise to match. Highest urine production at rest, less in exercise and least in emotional stress 1. Vascular: – myogenic (Bayliss): intrinsic property of smooth muscle -tendency to contract when stretched (TRPC channels)- SAME AS IN ARTERIOLES 2. Glomerulo-vascular: detection of [NaCl] in distal tubule by juxtaglomerular apparatus: if [NaCl]↑=filtering too much → vasoconstriction (adenosine- paradoximal, in other vascular beds it dilates) or dilation (NO) of afferent arteriole (. Brings each glomerulus into appropriate operating range (so that we’re not too dependent on capillary length)

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7
Q

• discuss how GFR can be regulated independent of RBF;

A

• PCap can be regulated either on afferent or efferent arterioles (due to constriction/dilation of smooth muscle) – Afferent vessel constriction:RBF↓ and GFR↓ – Afferent vessel dilatation: RBF↑ and GFR↑ – Efferent vessel constriction: RBF↓ but GFR↑ (blood flow stays in glomerulus- increased Pgc [glomerular pressure] – Efferent vessel dilatation: RBF↑ but GFR↓ (RESISTOR IN SERIES, HENCE INCREASED RESISTANCE REDUCE FLOW)

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8
Q

• recognise VSMC mechanisms resulting in renal vasomotion.

A

SIMILAR TO ARTERIOLES- Blood flow regulation mediated by endothelial - smooth muscle interactions…except adenosine paradoxical… • Endothelial - smooth muscle interactions • Constriction: Endothelin, AT1 • Dilation (see earlier): – Several pathways produce NO within EC, but also PGI/E and EDHF. – Endothelial mediators diffuse to smooth muscle cells: cGMP↑ → IK↑; PGI/E; EDHF

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9
Q

What happens in kidneys in glomerulonephritis and kidney donation

A

glomerulonephritis causes destruction/thickening of basal membrane with changes in its electrical charge resulting in protein loss (proteinuria; anuria). Compensation- when one kidney is lost, within a few days, functional compensation via hypertrophy of remaining glomeruli (reserve)

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10
Q

What keeps the filter clean?

A

Molecules entrapped in glomerular filter are BELIEVED to be eliminated by • glomerular podocytes (pinocytosis, endocytosis) and • phagocytic mesangial macrophages (see glomerulonephritis).

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11
Q

Give examples of vascular modulators

A

Vascular Modulators of RBF • Constrictors: – Sympathetic nerves: α1-adrenoreceptors – Angiotensin II (via AT1 receptor) – Endothelin – Adenosine (paradoxical in this vascular bed…) • Dilators – Prostaglandins (PGI2, PGE2) – NO from endothelia – Bradykinin – Dopamine – Angiotensin II (via AT2 receptor)

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12
Q

Stricker Summary

A

Take-Home Messages • Filtration results from Peff that arises from difference between PCap and PInterst plus πColosm. • PCap is constant over a wide range (autoregulation). • Autoregulation of RBF is invoked by – changes in MAPr (myogenic) and/or – changes in [NaCl] via the juxtaglomerular apparatus. • GFR can be regulated independent of RBF by afferent/ efferent vessel constriction: GFR↓ or ↑. • Blood flow regulation mediated by endothelial - smooth muscle interactions. • At single nephron level: [NaCl]↑ → R↑ → GFR↓: homeostasis to keep filtration constant.

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13
Q

MCQ Jonathan Miles, 50 y old, has been acutely administered a vasodilator drug that causes a 50% decrease in renal efferent arteriolar resistance with no change in afferent arteriolar resistance or arterial pressure. As compared to normal, which of the following rows best describes the expected changes:

A

dilation of efferent arteriole RBF increase GFR decrease Pcap should decrease (backup of blood) πColosm (efferent) should probably decrease (due to increased water in efferent??) B

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