Physiology of Nephron By Dr Abdel Aziz M

Physiology of Nephron By Dr. Abdel Aziz M. Hussein Assist Prof of Medical Physiology

Kidneys Urinary System

Overall Functions of Kidneys

Overall Functions of Kidneys Homeostatic Endocrinal Excretory Kidney Functions Regulatory Metabolic

1. Homeostatic Function • Kidneys keep the constancy of the internal environment (ECF) regarding; 1. Total body water 2. Tissue fluid osmolarity 3. Electrolytes Na, K, Ca etc……. 4. p. H Intake Kidney Input Output

2. Excretory Function • Kidneys get rid of 1. Metabolic waste products e. g. urea, uric acid & creatinine. 2. Many drugs and toxins Chronic renal failure → accumulation of these metabolites (uremia)

3. Regulation of ABP Through; a) Renin - angiotensin system V. C. ↑ ABP Aldosterone Angiotensin II ACE Angiotensin I Renin Angiotensinogen Drop of ABP

3. Regulation of ABP b) Production of vasoactive substances e. g. PGs and kinins. c) Control of Na and Water excretion Vasoactive substances e. g. kinins and PGs Controlling of Na and Water excretion

4. Endocrinal Function • Kidneys secrete; Erythropoietin from interstitial cells around PTC Activation of Vit D 1, 25 DOCC kinins and PGs Renin

5. Metabolic Functions Breakdown of insulin and glucagon Gluconeogenesis in fasting and starvation Do not Forget (RHEEM)

Functional Anatomy of Kidney

Functional Anatomy of Kidney Weight : 150 gm Capsule: tough and fibrous (limit its distension) Cross section: Capsule Outer Cortex inner Medulla

Functional Anatomy of Kidney • Glomeruli • PCT • DCT • LH • CDs • Vasa recta Cortex Medulla

Nephron

Nephron Def. , • It is the structural and functional unit of the kidney Number: • one million nephrons in each kidney Components : A) Renal or Malpigian Corpuscle B) Renal Tubule

Renal Corpuscle Renal Tubule Nephron Components

Renal Blood Supply

• Short • Wide • Direct branch of aorta

Renal Blood Flow Value: • 1200 ml/min or 4 ml/ 1 gm kidney tissues Significance: • Is high to ensure high GFR NOT to supply excess O 2 for excess metabolism

Juxta-glomerular Apparatus

Juxta-glomerular Apparatus Components:

Macula Densa Function • Monitor Na. Cl concentration in DCT (stimulated by low Na. Cl) ↓ ↑GFR

Juxta-glomerular cell Function • A) Synthesis, store and release of renin • B) acts as Baroreceptors (detect tension in wall of afferent arterioles) JG cells ↓ wall tension Renin ↓ Renal Blood Flow

Extra-glomerular Mesangial cell or Lacis (Polkisson) Function • Form functional syncitium with macula densa and JG cells

Functions of JGA • The only function of JGA is synthesis and secretion of renin Actions of Renin: V. C. Thirst and salt appetite Stimulates Na reabsorption from PT Stimulates ACTH, ADH, etc…. Increase force of myocardial contraction Angiotensin II ACE Angiotensin I Renin Angiotensinogen Stimulates Na and H 2 O reabsorption from intestine Aldosterone

Urine Formation

Urine Formation Filtration Reabsorption Secretion Urine

Glomerular Membrane

Glomerular Membrane Def. , • It the membrane through which the plasma is filtered Composition: 3 layers; 1. Capillary endothelium 2. Basement membrane 3. Capsular epithelium

Glomerular Membrane

Glomerular Filtration Blood Capillary endothelium Basement Membrane Podocytes slits Bowman Capsule Blood Cells Plasma proteins Plasma solutes

Glomerular Filtration Blood Capillary endothelium Basement Membrane Podocytes slits Bowman Capsule

Glomerular Filtration Def. , • It is an ultrafiltration since it is plasma minus plasma protein and cellular elements while simple filtration excludes only cellular elements.

Glomerular Filtration Dynamics: • Glomerular Filtration is formed by the forces of filtration as many capillary filtrate in the body (Starling's forces of filtration). • They are 4 forces; v 2 Hydrostatic pressures v 2 Oncotic pressures

Glomerular Filtration Glomerular capillary Glomerular Hydrostatic Pressure (Gp) Glomerular Oncotic Pressure (Gπ) Capillary endothelium Basement Membrane Podocytes slits Bowman Capsule Bowman oncotic Pressure (B π) Bowman Hydrostatic Pressure (Bp)

Glomerular Filtration Gp = 60 mm. Hg Gπ = 32 mm. Hg Bπ = 0 mm. Hg Help Filtration Gp = 18 mm. Hg Oppose Filtration

Glomerular Filtration Rate (GFR)

Glomerular Filtration Rate Def. , • Volume of plasma filtered by both kidney per unit time Value: – 125 ml/min – 180 L/day Significance of High GFR: • To ensure processing of plasma (3 L) about 60 times/day (since daily GFR = 180 L/day prevents accumulation of metabolites.

Glomerular Filtration Rate Causes of high GFR: 1) High capillary hydrostatic P. : • It is about 45 - 60 mm. Hg in glomerular capillary High GP: 1. Efferent arteriole → narrower than afferent arteriole 2. Glomerular capillaries →present between two arteries

Glomerular Filtration Rate Causes of high GFR: 2) High KF (filtration coefficient) 3) High RPF. : • It is about 600 ml/ min. RBF

Glomerular Filtration Rate Factors Affecting GFR: Glomerular hydrostatic pressure • About 45 – 60 mm. Hg • Help GFR Bowman’s capsular hydrostatic pressure • About 18 mm. Hg • Oppose GFR Oncotic pressure of plasma protein • About 32 mm. Hg • Oppose GFR Renal plasma flow (RPF) • About 650 ml/min • Help GFR Filtration coefficient • About 4 ml/min/ 1 mm. Hg/ 100 gm Help GFR •

Functions of Renal Tubules

Renal Tubules

Proximal Tubules

1. Glucose, amino acids, vitamins, protein → 100% 2. HCO 3 - → 90% 3. inorganic phosphate → 80% 4. Na+ & water → 2/3 or 65% 5. K+, Ca 2+, Mg 2+ & urea → Variable amount Reabsorption

Organic solutes as PAH, drugs, various amines and ammonia. Secretion

Overall Functions of Proximal Tubules a) Reabsorption of: 1. All filtered glucose, amino acids, vitamins, protein and Kreb’s cycle intermediates. 2. About 2/3 of filtered load of Na+ & water. 3. About 90% of the filtered load of HCO 3 -. 4. About 80% of the filtered inorganic phosphate. 5. Variable amount of K+, Ca 2+, Mg 2+ & urea. b) Secretion of • Organic solutes as PAH, drugs, various amines and ammonia.

Loop of Henle

Overall Functions of LH 30% Ca 65% Mg 10 % K 15% Water Urea

Overall Functions of Proximal Tubules a) Reabsorption of: 1. 15 % of filtered water from DLH. 2. 30% Ca 3. 65% Mg Thick ALH 4. 10 % K b) Secretion of • Urea by thin ALH c) Concentration of urine by forming counter current multiplier system

Distal Segment of Nephron

Overall Functions of Distal Segment 1. 2. 3. 4. 5. Final adjustment of urine formation. Reabsorption of 7 -10% of filtered load of Na+. Reabsorption of 10 -15% of filtered lead of water. Secretion of variable amount of H+ & K+. Major control site for Na+, K+, Ca 2+ & acid-base balance of body. • Many of these functions are controlled by hormones • Na reabsorption controlled by aldosterone • H 2 O reabsorption controlled by ADH

Summary of overall functions of renal tubules

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