Renal Physiology

Suzan Arafat Kamel, DVM, PhD

Medical Physiology Department

School of Medicine, Assiut University

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Objectives

• Understand the basic functions of the urinary system

• Be familiar with the macroscopic and microscopic anatomy and physiology of the kidney

• Describe the process of urine formation

• Understand the process and control of filtration and understand the regional tubular transport

• Understand the micturition reflex

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I. Functions of the Urinary System

A. Controls ion concentration of the plasma

B. Regulates plasma volume & volume of interstitial fluid

C. Regulates plasma osmolarity

D. Regulates plasma pH (H+)

E. Removes waste products and foreign substances from the plasma

F. Endocrine Functions. Erythropoietin, Renin, Vitamin D3

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Anatomy of Urinary System

A. Kidneys

B. Ureters

C. Urinary Bladder

D. Urethra

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Macroscopic Anatomy of the Kidney

1. Cortex

2. Medulla

a. Renal Pyramids

i. Made of nephrons (400 000 in each kidney in dogs and 4000 000 in each kidney in cattle)

ii. Nephrons are the functional units of the kidney

b. Renal Pelvis

i. Collects fluid produced by nephrons via the minor, then major calyx

ii. Delivers fluid to the ureter 5

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Microscopic Anatomy of the Kidney: Nephron

1. Nephrons are either a. Cortical Nephrons

b. Juxtamedullary Nephrons

2. Nephron anatomy is key

for understanding nephron

function

Figure 18.4

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Structure of the Nephron

1. Renal corpuscle

i. Glomerulus

ii. Bowman’s capsule

2. Renal tubules

i. Proximal convoluted tubules (PCT)

ii. Loop of Henle:

a. Descending limb

b. Ascending limb

iii. Distal convoluted tubules (DCT)

3. Collecting duct

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Blood Flow in the Nephron

Both kidneys receive ~ 20% (400 ml) of cardiac output at rest in dogs.

1. Afferent Arteriole

2. Glomerulus

(Glomerular Capillary)

3. Efferent Arteriole

a. Peritubular Capillaries

b. Vasa Recta

4. Renal Venules and Veins

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Renal Corpuscle

• Beginning of the nephron

• Consists of :

– Glomerulus : Capillary network where filtration from the blood to the nephron begins.

• Afferent arteriol

• Efferent arteriol

a. Bowman’s capsule: membrane that surrounds the glomerulus and receives the filtrate from the glomerular capillaries

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Juxtaglomerular Apparatus (JGA)

• Where the efferent and afferent arterioles are in contact with DCT.

• Cells

1. Macula Densa: in distal tubul

2. Juxtaglomerular Cells (JG): the adjoining smooth muscle cells in the afferent arteriolar wall. They form, store and secrete renin. They are sensitive to pressure changes within the arterioles (intrarenal baroreceptors)

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IV. Urine Formation: 1. Filtration (Glomerular

Filtration). Bulk flow of fluid from glomerular capillary into Bowman’s Capsule

2. Reabsorption. Transport of molecules from the renal tubules back into the capillaries

3. Secretion. Transport of molecules from the capillaries to the renal tubules

The net effect of these processes is equal to EXCRETION

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1- Filtration A. Filtration Membrane. Determines movement of

protein-free plasma from glomerular capillary into Bowman’s Capsule

1. Glomerular Capillary Endothelium:

a. Fenestrated capillaries

2. Basement membrane

3. Epithelial cells of Bowman’s

Capsule:

a. Podocytes

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Forces that Determine Filtration

1. Glomerular Capillary Hydrostatic Pressure

2. Bowman’s Capsule Osmotic Pressure

3. Bowman’s Capsule Hydrostatic Pressure

4. Glomerular Capillary Osmotic Pressure

Which 2 forces favor filtration? Which 2 forces oppose filtration?

You are comparing two compartments: Glomerular Capillary & Bowman’s Capsule

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Glomerular Filtration Rate (GFR)

• It is the volume of fluid filtered from the glomerular capillaries into Bowman’s capsule per minute.

Mammals GFR

Horse 380 ml/min

Dog 55 ml/min

Human 125 ml/min

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Factors Regulating GFR • Under physiological conditions, the factors

regulating GFR, that is, glomerular hydrostatic pressure and renal blood flow, are primarily adjusted by:

– Autoregulation

– Angiotensin II

– Sympathetic nerve fibers

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1- Autoregulation

• It is mediated by 2 different mechanisms:

1. Myogenic regulation:

i. An increase in blood pressure stretches mechanoreceptors in arterioles

ii. This stretch stimulates vasoconstriction of the afferent arteriole

iii. Vasoconstriction decreases blood flow through the vessel

iv. A decrease in blood flow through the afferent arteriole decreases glomerular capillary hydrostatic pressure and thus brings GFR back down to normal

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2. Tubulo-glomerular feedback:

i. An increase in GFR causes an increase in fluid flow through the distal tubule.

ii. Stretch receptors in the macula densa detect the increased flow and increased fluid osmolarity and signals the juxtaglomerular cells of afferent arteriole to contract

iii. When those cells vasoconstrict, distal flow through the afferent arteriole is reduced, so GFR is ________________.

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2- Renin Angiotensin System

• Decrease in arterial blood pressure and extracellular fluid volume.

• JG cells of the afferent arteriol release renin. Renin acts on angiotensinogen (made in liver) to be converted into angiotensin II (AT II) by ACE (angiotensin converting enzyme)

• Angiotensin II:

– is a powerful vasoconstrictor that causes a rise in mean arterial BP

– It stimulates adrenal cortex to release aldosterone.

– There are more AT II receptors on the efferent arteriole than the afferent resulting in constriction of efferent arterioles reduces the hydrostatic pressure in the peritubular capillaries that promotes tubular reabsorption

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Juxtaglomerular Apparatus (JGA)

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H+ excretion

Aldosterone Regulation

Circulating angiotensin II level

is the most important regulator

of aldosterone secretion!

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(liver)

Juxtaglomerular Cells & Macula Densa

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GFR Regulation

Slightly 24

GFR Regulation

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3- Autonomic Regulation of GFR

• In response to excessively LOW blood pressures in situations of crises and stress e.g in hemorrhage. It leads to increase in sympathetic activity.

• The net effects are:

– Reduced blood flow to the kidneys (due to contraction of both afferent and efferent arterioles)

– Moderate reductions in the excretion of waste products

– Increased conservation of water and salts

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Tubular Reabsorption

The transport of the substances from the tubular lumen across epithelial cells to the peritubular capillaries

It is highly selective process and 70% occurs in PCT

It includes passive and active mechanisms

Active reabsorption includes primary and secondary

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Primary Active Transport

• Transport against electrochemical gradient and is coupled directly to an energy source as hydrolysis of ATP.

• E.g.

– Na+-K+ ATPase

– H+ ATPase

– H+-K+ ATPase

Secondary Active Transport

• Transport against electrochemical gradient and is coupled indirectly to an energy source

• E.g.

– Glucose

– Amino acids

– Phosphate

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Primary Active Reabsorption

• Na+-K+ pumps in the basolateral membrane transport Na actively out of the cells. K+ is transported in the opposite direction. The Na+ concentration is therefore low, and the K+ concentration is high. K+ diffuses out of cells causing an excess of negative charge inside the cells. The negative charge and the low Na + concentration inside the cells lead to diffusion of Na + from the tubular lumen through ion channels into the epithelial cells

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Secondary Active Transport • Glucose or AA is transported through the apical membrane of

the epithelial cell by sec. active reabsorption, coupled to Na transport (co-transport). This increases the intracellular glucose or AA concentration causing facilitated diffusion of them into the interstitial fluid.

• H + is secreted by secondary active transport with Na + (counter-transport)

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Passive Reabsorption

• Urea, negative ions and many other substances are passively reabsorbed due to differences in concentration and electrical potential between the tubular and interstitial fluid.

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Water Reabsorption

• Obligatory water reabsorption occurs at the PCT by osmosis where water flows in the same direction as the dissolved substances

• Facultative reabsorption of water occurs at the DCT and collecting tubules under ADH control.

PCT

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Renal handling of Glucose

• Normally, all filtered glucose is reabsorbed by PCT

• Glucosuria occurs when the plasma glucose concentration is more than twice the normal.

• The renal threshold of glucose is the lowest plasma concentration at which glucose can be detected in the urine.

• Transport maximum of glucose is about 170 mg/min in dogs and 375 mg/min in humans

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Transport maximum (TM) system Is the maximum rate at which a filtered substance can be

reabsorbed from the tubules General characteristics: • Carriers are easily saturated • Carriers have high affinity for the substance • Low back leak: back leak refers to the back diffusion of the substance into the tubule after it is reabsorbed into the interstitium. Minimal back leak of glucose occurs because the proximal tubule is not permeable to glucose

Example: proximal tubular reabsorption of glucose

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