HRM - Lecture 6: Functions of the urinary system

- urea

- uric acid

- hormone metabolites

- toxins

- drugs

- ions

Name a 5 things excreted by the kidneys

- Blood urea nitrogen (BUN)

- creatinine

- potassium

- phosphate

Name a few parameters that increase in renal failure

- renin (technically an enzyme, but important for angiotensinogen -> angiotensin I)

- 1,25-Dihydroxycholecalciferol (Vit D3)

- erythropoeitin

Name 3 hormones produced by the kidneys

- control amount of water lost (lowers volume+pressure)

- erythropoietin (increase RBC)

- renin secretion (increas BP)

How do the kidneys control blood volume and pressure?

- Na+, K+, Cl- by controlling amount released

- Ca2+ via calcitriol synthesis

How do the kidneys regulate plasma ion concentration?

By controlling the amount of H+ and HCO3- excreted

How do the kidneys regulate pH?

- 25% of CO, highest perfusion/weight of any organ

- From renal artery - from abdominal aorta

- High rate of blood supply for high glomerular filtration

-

Describe the renal blood supply

Function as osmotic exchanger. It helps maintain a hypertonic interstitial fluid in the juxtamedullary nephrons

How do the vasa recta function in urine production?

glomerulus: 60mmHG - a lot of force, favours filtration (pushing fluid out)

peritubular: 20mmHg - less force, favours reabsorption

Compare the pressure of the glomerulus and the peritubular capillaries. What is the main effect of these pressures?

Via a single cilium, functioning as chemo- and mechano-receptor, protruding from the apical surface into the lumen

How do cells of the nephron sense fluid composition and flow rate?

85% cortical

15 % juxtamedullary

What proportion of nephrons is cortical and juxtamedullary respectively?

left: juxtamedullary: lower (closer to medulla), longer loop of henle, vasa recta present

right: cortical: higher (in cortex), shorter loop of henle, no vasa recta, only peritubular capillary network

What type of nephron is the left and the right? Give reasons for your answer.

Their contraction is coupled to basement membrane contraction which lowers surface area for filtration and decreases GFR

How do intraglomerular mesangial cells control GFR (glomerular filtration rate)?

- renin secreting cells

- granular cells

What are two other names for epitheloid cells of the juxtaglomerular apparatus?

- in afferent arteriole close to glomerulus

- modified vascular smooth muscle resembling epithelium

Describe the structure and location of the granular cells

extraglomerular mesangial cells located between afferent and efferent arteriole

What are the Lacis cells?

- Salt detection in DCT

- cause constriction of afferent arteriole in response to high sodium chloride and decrease GFR

- signal renin release from juxtaglomerular cells when sodium is low

What is the function of the macula dense?

- fenestrated endothelium

- basement membrane

- filtration slits created by pedicels of podocytes

All have a negative charge and are selective in filtration

Briefly describe the filtration barrier of the glomerulus

8nm

What is the cutoff size for particles to pass through endothelial fenestrations?

- electrolytes

- water

- vitamins

- hormone metabolites

- amino acids

- fatty acids

- glucose

- urea

- uric acid

- creatinine

Name 5 things that can pass through fenestrations

- proteins

- large anions

- blood cells

- protein bound electrolytes or hormones

Name 4f things present in plasma that can't pass through fenestrations

This allows passage of neutral and positively charged particles and rejects negatively charged particles such as proteins

How does negative charge affect filtration?

The filtration slit diaphram is thin and made up of a number of proteins

Describe the filtration slit barrier

- Nephrin

- NEPH-1

- NEPH-2

- podocin

What are the proteins of the filtration membrane extracellularly?

- CD2-AP

- alpha-actinin 4

What are the proteins of the filtration membrane intracellularly?

a: Na+ is actively transported out and water and Cl- follow

b: solute concentration in ISF very high causing further exosmosis from loop of henle

c: salt is drawn out actively and through diffusion in ascending loop as solute concentration in ISF drops

d: tubule exits into collecting duct which passes through high solute concentration levels in the kindey causing further exosmosis

Describe briefly what happens at points 2 a,b,c,d

Glomerular filtration rate is the sum of all filtrate production by all nephrons per unit time

Define GFR

Renal blood flow is the total amount of blood that flows through the kidneys

Define RBF

Renal plasma flow is the total amount of plasma that flows through the kidneys

Define RPF

GFR/RPF: usually about 20% of plasma is filtered

Define filtration fraction

The ultrafiltration coefficient: size of capillary bed x permeability of capillaries

What is Kf?

Kf x net filtration pressure

What are the factors of GFR?

Lower size of capillary bed (glomerular destruction)

In diseae states, which factor of GFR is most commonly affected?

Net filtration pressure = Glomerular HP - Glomerular OP - Bowman's capsule pressure

What are the factors of net filtration pressure?

Virtually no proteins in filtrate

Why is Bowman's colloidal osmotic pressure not a factor of net filtration rate?

increase GFR

How does dilation of the afferent arteriole affect GFR?

decrease GFR

How does dilation of the efferent arteriole affect GFR?

decrease GFR

How does constriction of the afferent arteriole affect GFR?

increase GFR

How does constriction of the efferent arteriole affect GFR?

- neural control

- hormonal control

- autoregulatory control

What are the 3 main mechanism types that regulate GFR?

This is intrinsic to the kidney. It is comprised of the arteriole myogenic mechanism and the tubuloglomerular feedback

Briefly describe autoregulatory control of GFR

Made up of the renin-angiotensin system

Briefly describe hormonal control of GFR

Mainly controlled by sympathetic input which constricts vessels and decrease GFR

Briefly describe neural control of GFR

The arterioles contain smooth muscle which contracts when stretched and relaxes when stretch dissipates. This reduces diameter variation

What is the myogenic mechanism?

This refers to the macula dense cells and Na+ level regulation.

Increased GFR -> increased NaCl in tubule fluid at macula densa level -> increased uptake of NaCl by MD cells -> increased adenosine and ATP in MD cells -> ATP binds to P2X receptor and adenosine binds to adenosine A1 receptors in smooth muscle of afferent arteriole -> increased intracellular Ca2+ -> contraction of smooth muscle vasoconstriction -> return of normal (lower) GFR

What is the tubuloglomerular feedback? Describe the steps

source: adrenal medulla and sympathetic nerves

site of action: beta receptors on afferent arterioles

action: reduced RBF and GFR

Name source, site of action and effect for Epinephrine and norepinephrine

Source: renal endothelium, mesangial cells and distal tubular cells

site of action: blood vessels

action: vasoconstriction and reduced GFR

Name source, site of action and effect for Endothelin

source: Converted in blood from ATI (mostly in lung by ACE)

site of action: afferent and efferent arterioles, particularly efferent (in kidney), brain, adrenal cortex

actions:

- powerful systemic vasoconstriction

- lower RBF but similar GFR

- Stimulate aldosterone and ADH (and ACTH) release -> increased sodium and water reabsorption -> increased blood pressure

- stimulate thirst and salt craving directly in the brain

Name source, site of action and effect for Angiotensin II

source: Macula densa in response to high Na+

site of action: afferent arteriole

action: reduced RBF and GFR

Name source, site of action and effect for Adenosine

source: widespread - mostly local release during renal ischaemia

site of action: renal vessels

action: vasodilation and increased RBF

Name source, site of action and effect for prostaglandins

source: myocardial cells

site of action: afferent and efferent arteriole

action: dilate afferent, constrict efferent. increase GFR, similar RBF, supression of Na+ reabsorption in PCT, inhibit ADH and aldosterone secretion -> natriuresis -> decrease BP

Name source, site of action and effect for ANP and BNP

Glomerular filtration - tubular reabsorption + tubular excretion

What are the factors of urinary excretion?

1. paracellular

2. transcellular

Name the two pathways

Bulk flow

What is the name of transfusion of water and solutes from ISF to blood?

- primary active transport

- secondary active transport

- pinocytosis

- passive diffusion

Name 4 types of cellular transport

- Na+/K+ ATPase pervasive in basolateral side of cells (side facing interstitium)

- Sodium actively transported into interstitium and from there enters capillaries.

- Cl- and water follow sodium

How is sodium reabsorbed in the tubules?

- Secondary active transport

- SGLT (sodium-glucose transport protein) transports Na+ down its gradient and pulls glucose together with it against its gradient

How does glucose move from the lumen into the epithelial cells of the tubule?

90% SGLT2

(10% SGLT1)

Which is the major subtype of SGLT?

H+/Na+ exchanger exports one H+ into lumen and brings in one Na+

How can H+ be concentrated in the lumen of the tubule?

Secondary active: Sodium cotransport

How are amino acids reabsorbed?

Pinocytosis via surface receptors

How are proteins reabsorbed in PCT?

Follows positive charge of Na+ (Passive reabsorption, not active)

How is urea reabsorbed?

65% - actively established sodium gradient is the main driver of reabsorption of other solutes and water

How much sodium chloride is typically reabsorbed under normal circumstances. What is the significance?

- thin descending

- thick descending

Which regions of the loop of henle are permeable to water?

- no significant reabsorption in thin ascending

- thick ascending reabsorbs sodium, chloride and potassium via NKCC2 symporter (1Na+,1K+, 2Cl-)

- ROMK channel allows K+ to be secreted after absorption through NK2C

- Ca2+, HCO3-, and Mg are also absorbed

- paracellular reabsorption of Na+, Mg2+, Ca2+, K+

Describe reabsorption in the ascending limb

ADH

Which hormone stimulates NKCC2?

H+ excreted, Cellular H+ exchanged for luminal K+, luminal K+ passively diffused into interstitium on basal surface,

Intracellular HCO3- exchanged for interstitial Cl-,

passive diffusion of Cl- into lumen

Which solutes are modulated by type A intercalated cells?

Intracellular HCO3- (from carbonic acid) excreted in exchange for luminal Cl-,

passive diffusion of Cl- in to interstitium,

H+ (from carbonic acid) reabsorbed at basal surface,

Intracellular H+ exchanged for interstitial K+ at basal surface,

passive diffusion of K+ out to lumen

Which solutes are modulated by type B intercalated cells?

In the collecting duct

Where are the intercalated cells?

- sites: principal cells, intercalated cells

- effect at principal cells: Na+ reabsorption, K+ secretion

-effect at intercalated cells: increased H+ secretion

How does aldosterone act on reabsorption (site and effect)?

- sites: PCT, TAL, DCT,

- effect for all: increased Na+ reabsorption, increased H+ secretion

How does angiotensin II act on reabsorption (site and effect)?

- site: DCT, collecting tubule, collecting duct

- effect: increased water reabsorption

How does ADH act on reabsorption (site and effect)?

- site: DCT, collecting tubule, collecting duct

- effect: decreased sodium reabsorption

How does ANP act on reabsorption (site and effect)?

- site: PCT, TAL, DCT

- effect: decreased phosphate increased Ca2+ reabsorption

How does PTH act on reabsorption (site and effect)?

enhances Na+ reabsorption in PCT, stimulates apical sodium-hydrogen exchanger and basal Na/K pump

How does the sympathetic nervous system act on reabsorption (site and effect)?

decreased sodium reabsorption

How does arterial pressure act on reabsorption (site and effect)?