1 Lecture-5 Dr. Zahoor. Objectives – Tubular Secretion Define tubular secretion Role of tubular...

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TUBULAR SECRETION

Lecture-5Dr. Zahoor

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Objectives – Tubular SecretionDefine tubular secretion

Role of tubular secretion in maintaining K+ conc.

Mechanisms of tubular secretion.

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• Three Basic Mechanisms (Renal Processes) Of Urine Formation include:1. Glomerular Filtration2. Tubular Reabsorption3. Tubular Secretion

URINE FORMATION

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TUBULAR SECRETION

Tubular Secretion is transfer of substances from the peritubular capillaries (capillaries surrounding the tubule) into the tubular lumen.

It helps to eliminate the compounds from the body

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Tubular Secretion

• First step is simple diffusion from peritubularcapillaries to interstitial fluid

• Entry from interstitial fluid to tubular cell can

be active or passive

• Exit from tubular cell to lumen can be active or passive

• Examples: potassium, hydrogen, organic acids,organic bases, NH3

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Calculation of Tubular Secretion

Secretion = Excretion - Filtration

H+, K+, NH3

Organic acids and bases

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Tubular Secretion

Tubular secretion is important for: Disposing of substances not already in the filtrate

Eliminating undesirable substances such as urea and uric acid

Getting rid of excess potassium ions

Controlling blood pH by secreting H+

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TUBULAR SECRETION

The most important substances secreted are

- Hydrogen ion - Potassium ion - Para Amino Hippuric acid ( PAH) - Organic anion and cations - Drugs e.g. penicillin, aspirin,

Cemitidine - Hormones e.g. erythropoietin,

renin

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TUBULAR SECRETION

Hydrogen Ion Secretion: Hydrogen Ion Secretion is important in acid

base balance Hydrogen ion is secreted in the tubular

lumen and eliminated from the body in the urine

H+ ion is secreted in proximal, distal, and collecting tubule

We will discuss H+ ion secretion in detail with acid base balance.

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TUBULAR SECRETION

Potassium Ion Secretion: K+ ion secretion is controlled by

aldosterone 98% of K+ is intracellular (ICF – K =

140meq/l) ECF – K+ = 4meq/l Slight changes in ECF – K+ can affect

the membrane excitability, therefore, plasma K+ concentration is tightly controlled by the kidneys

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TUBULAR SECRETION OF K+

K+ is actively reabsorbed in PCT Na+ is actively reabsorbed and K+ is

actively secreted by principal cells in the distal and collecting tubules and controlled by Aldosterone.

Intercalated cells in DCT and CT actively secrete H+ and K+ ion

Intercalated cells work for acid base balance

Potassium handling by nephron

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MECHANISM OF K+ SECRETION

K+ is secreted in the principal cell of DCT and CT. It is coupled to Na+ reabsorption by energy dependent basolateral Na+ - K+ pump

14K+ ion secretion

Principle cells in Late DCT & CT

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CONTROL OF K+ SECRETION

Most important control mechanism for K+ secretion is by aldosterone

Aldosterone causes Na+ reabsorption and K+ secretion by principal cells

Increased K+ concentration directly stimulates the adrenal cortex to increase aldosterone secretion

Decreased K+ concentration in plasma – causes decreased aldosterone secretion

NOTE – Aldosterone secretion by Na+ is through Renin-Angiotensin Aldosterone mechanism

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Control Of Aldosterone Secretion By K+ and Na+

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Sodium Reabsorption

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Mechanism of Aldosterone Action

Aldosterone : Aldosterone causes Na+ re absorption and K+ secretion

by principle cell

Aldosterone causes increased Na+ entry through luminal membrane into principal cells

Aldosterone causes Na+ pumping out of principal cells by Na+-K+ pump into interstial fluid at basolateral membrane

Aldosterone causes K+ entry into the cell by Na+ - K+ pump, it increases the concentration of K+ in the cell, which is driving force for K+ secretion (passively)

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Changes in Distal K+ Secretion Causes of

increased Distal K+ Secretion

- High K+ diet- Hyperaldosteronis

m- Alkalosis- Thiazide diuretics- Loop diuretics

Causes of decreased Distal K+ Secretion

- Low K+ diet- Hypoaldosteronism- Acidosis- K+ - sparing

diureticsNOTEHyperaldosteronism – Hypokalemia Hypoaldosteronism – Hyperkalemia

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EFFECT OF H+ SECRETION ON K+ SECRETION

During acid base regulation, intercalated cells in DCT secrete either K+ or H+

When there is acidosis, H+ ions secretion is increased and K+ secretion is decreased

This decreased secretion of K+ leads to K+ retention in the body fluids, therefore, in acidosis, there is hyperkalemia {increased K+}

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IMPORTANCE OF REGULATING PLASMA K+ CONCENTRATION

K+ plays important role in membrane potential

K+ changes in ECF, when there is increase or decrease in K+ level, it can affect the heart and can cause decreased cardiac excitability, decrease conduction, cardiac arrhythmia, fibrillation

K+ changes not only affects cardiac muscle but it also affects skeletal muscle and nerve conduction

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EFFECT OF DECREASED K+

Decreased K+ causes hyperpolarization, which decreases the excitability of the nerve

In Skeletal muscle, K+ depletion causes muscle weakness

K+ depletion causes abdominal distension due to smooth muscle dysfunction

Organic Anion and Cation secretion

Proximal tubule contains two types of secretory carriers1. For organic anions2. For organic cations

Organic ions such as Prostaglandin, epinephrine – after their action removed from blood

Non filterable organic ions also removed Chemicals, food additives, non nutritive

substances Drugs – NSAID, antibiotics

PAH –EXAMPLE OF SECRETION

PAH is an organic acid Used for measurement of renal plasma

flow Both filtered and secreted PAH transporters located in peritubular

membrane of proximal tubular cells.

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Thank you