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RENAL PHYSIOLOGY,

HOMEOSTASIS OF FLUID COMPARTMENTS (4)

Dr. Attila Nagy

2018

Intercalated cells

Intercalated cells secrete either H+ (Typ A) or

HCO3- (Typ B).

In intercalated cells Typ A can be observed the H+ Sekretion

through H+-ATPase or in K+-deficit through H+/K+

ATPase.

In intercalated cells Typ B HCO3- secretion is through

Cl-/HCO3- antiporter. The accumulated Cl- leaves the cell

through basolateral Cl- channels.

Paracellular Cl- resorption is also possible.

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Principal cell

Intercalated cell

Typ A

Intercalated cell

Typ B

Water household

Water intake 2100-3400 ml/day

Fluid intake 1000-2000 ml/day

Water content of foodstuffs 800-1000 ml/day

Oxidative water 300-400 ml/day

Water output 2100-3400 ml/day

Insensible perspiration 800-1000 ml/day

sensible perspiration, sweating 200 ml/day

Stool 100-200 ml/day

Urine 1000-2000 ml/day

Minimal urine output 500-600 ml/day (650 mosm solute/day).

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• Physiology of thirst

1. dryness of the mouth

2. angiotensin II

3. hypothalamic osmoreceptors

Control of water intake (hyperosmosis and hypovolaemy)

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Control of loss of water

Regulation of vasopressin

(AVP) production

Renin-angiotensin system stimulates Atrial Natriuretic

Hormon inhibits the AVP production.

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Effects of AVP:

-Water reabsorption from the collecting duct through

Aquaporin-2 water chanels (V2/cAMP)

-V1/ITP-Ca2+ vasoconstrictor effect

-V3 receptor in the ACTH producing neurons of the anterior

pituitary gland

The water transport is regulated by the anti-diuretic

hormone (ADH).

The collecting duct is relatively impermeable to

water and urea in the absence of ADH

In the presence of ADH the water permeability of the

whole collecting duct and the urea permeability of its

papillary part is greatly increasing

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In the absence of ADH the osmolality of the fluid that

leaves the collecting duct is 70 mosm/kg (50 mosm/kg

urea and 20 mosm/kg electrolyte).

In the absence of ADH or V2 ADH receptor up to

15% of the filtrated water will be excreted (max. 26 liter/day)

diabetes insipidus.

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ADH secretion

Increased by Inhibited by

1. High osmolarity of the blood 1. low osmolarity

2. Hypovolemia 2. Hypervolemia

(inhibits ANP secretion)

3. Standing 3. Lying in horisontal position

↓ ANP ↓ ↑ ANP ↑

4. venous stasis 4. Alcohol

5. pain, exercise

Osmolality of the tubular fluid

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The concentration and dilution of the urin

Depending on the need of the body the kidney can produce

1. highly concentrated (to 1.200 mOsm/l) or

2. strongly diluted urin (to 70 mOsm/l).

Factors influencing urine concentration:

Length of Henle loops

Percentage of long-looped nephrons compared to

short-looped ones

Urea

Flow through Henle-loop and collecting duct

Blood-flow through vasa recta

Prostaglandines (PGE2, PGD2)

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Concentration and Dilution of Urine

Countercurrent multiplication

Medullary gradient

300 mosm/kg-1200 mosm/kg

Medullary gradient originates from:

Horisontal gradient – Active Na+ reabsorption in the

ascending thick segment of the loop of Henle

Loop diuretics (i.e. Furosemide) abolishes the medullary

gradient

Vertical gradient (countercurrent) - Fluid movement in the

descending and ascending segment of the Henle-loop

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The motor of the concentrating of the urin is the

electrolyt transport in the loop of Henle

The most important function of the loop of Henle is the

bilding of hyperosmolar renal medulla.

The ascending thick segment resorbs actively Na and Cl,

practically without water resorption. These transports

decrease the osmolarity of the tubular fluid and increase the

osmolarity in the renal medulla.

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ACTIVE TRANSPORT

PASSIVE TRANSPORT

Urea transport in the nephronUrea-cycle

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Blood flow in the renal medulla

The hyperosmolarity and the medullar gratient would be

washed out quickly, if the blod flow and the form of blood

wessels would be conventional. The loop form structure of

Vasa Recta prevents the dilution of renal medulla.

Countercurrent system does not allow the quickly transport

of NaCl and urea.

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The concentration of urin will be inhibited through:

- Karboanhydrase inhibitor (Acetazolamide)

- Loop diuretics (Inhibition of Na+,K+,2Cl--symporters)

-Thiazide (Inhibition of Na+/Cl- cotransporter)

- ATII rezeptor antagonists (Losartan)

- Aldosteron antagonistsen (Spironolakton)

- Potassium deficit (inhibits the Na+,K+,2Cl--symporter)

- Hyperkalcaemia (Decreasing the permeability of tight junctions,

Ca2+-receptors inhibiting the Na+,K+,2Cl--symporter)

- Proteipoor nutrition

- Renal inflammation (Dilatation of Vasa recta)

- Increase of blood pressure

- Osmotic diuresis (filtration of no or partial resorbable osmotic active

substances)

- Diabetes insipidus

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Buffer systems in the urine

1. phosphate buffer

2. ammonia buffer

(3. bicarbonate buffer)

Urine pH: 4.0-8.0

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Phosphate buffer

HPO42- : H2PO4

– = 4:1 (pK= 6.8)

if the urin pH is equal to the pH of the arterial

Blood (7.4)

Titratable acidity

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Ammonia buffer

NH4+ ⇔ NH3 + H+ (pK = 9.3)

Glutaminase Glutamate dehydrogenase

Glutamine Glutaminic acid α-ketoglutaric

acid

NH3 NH3

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Solubility of NH3 and NH4+

NH3 rather soluble in lipids and diffuses passively

through membranes, NH4+ is a polar substance and

not able to diffuse through membranes.

The production of ammonia is regulated by the plasma

pH, through glutaminase activation.

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Ammonia transport in the proximal nephron

Passive diffusion in the tubular lumen (NH3)

Active transport Na+/H+ antiporter (NH4+)

Lumen Sejt Vér

Ammonia transport in the thick ascending limb of loop of

Henle. Na+-K+-2Cl- cotransporter reabsorbs NH4+ instead of

K+.

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Ammonia transport in the distal nephron

In principal cells the Na+/K+ pump could transport NH4+ instead of

K+ .

Principal cell

NH3 – NH4+ reaction in the distal tubule is coupled with H+

secretion and new bicarbonate production

PERITUBULAR SPACETUBULAR LUMEN

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Micturition(Learning objective: 58)

Upper urinary tract

- renal calyces

- renal pelvis

- ureter

Lower urinary tract

- urinary bladder

- urethra

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Micturition reflex

Stimulus: stretch (volume of the urine)

Receptor: stretch receptors

Afferents nerves: pelvic n. (parasympathetic)

Ctr: S2-4

Efferents nerves pelvic n. (parasympathetic)

Somatic innervation: pudendal nerve S1

Sympathetic innervation: hypogastric plex.

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sympatheticafferent

parasympathetic

afferent

vegetative

afferent

somato-motor

pelvic nerve

pudendal nerve

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sympathetic

medial pontine lateral pontine

Micturition

Detrusor contraction

sphincter relaxation

Retention

Detrusor relaxation

sphincter contraction

Supraspinal regulation:

Pontine

Mesencephalic

Hypothalamic

Cortical centers

Spinal transection