5. TUBULAR SECRETION

Download Report

Transcript 5. TUBULAR SECRETION

TUBULAR SECRETION
Lecture-5
Dr. Zahoor
1
Objectives –Tubular Secretion
 Define tubular secretion
 Role of tubular secretion in maintaining K+
conc.
 Mechanisms of tubular secretion.
2
URINE FORMATION
• Three Basic Mechanisms (Renal Processes) Of
Urine Formation include:
1. Glomerular Filtration
2. Tubular Reabsorption
3. Tubular Secretion
3
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
4
Tubular Secretion
• First step is simple diffusion from peritubular
capillaries 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
5
Calculation of Tubular Secretion
Secretion = Excretion - Filtration
H+, K+, NH3
Organic acids
and bases
6
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+
7
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
8
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.
9
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
10
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
11
Potassium handling by nephron
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
13
K+ ion secretion
14
Principle cells in Late DCT
& CT
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 ReninAngiotensin Aldosterone mechanism
16
Control Of
Aldosterone
Secretion By
K+ and Na+
17
Sodium Reabsorption
18
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)
19
Changes in Distal K+ Secretion
 Causes of increased
 Causes of decreased
Distal K+ Secretion
Distal K+ Secretion
- High K+ diet
- Low K+ diet
- Hyperaldosteronism
- Hypoaldosteronism
- Alkalosis
- Acidosis
- Thiazide diuretics
- K+ - sparing diuretics
- Loop diuretics
NOTE
Hyperaldosteronism – Hypokalemia
Hypoaldosteronism – Hyperkalemia
20
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+}
21
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
22
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
23
Organic Anion and Cation
secretion
 Proximal tubule contains two types of secretory
carriers
For organic anions
2. For organic cations
1.




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.
Thank you
26