Renal system

Parts of the urinary system:

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• Kidneys: contain the functional units to make urine

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• Ureters: carry urine formed by the kidney to the urinary bladder

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• Urinary bladder: store urine until released from the body

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• Urethra: conduct urine outside the body

General Functions of the kidneys:

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• Excretion of metabolic waste products such as Urea, Uric acid

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• Regulation of Water and electrolyte balance

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• Regulation of Body fluid volume and osmolarity

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• Regulation of Acid base balance

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• Regulation of Arterial pressure

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• Produce hormones (erythropoietin) or regulate the release of hormones from other organs (Vit D3 and aldosterone)

Nephron: is functional units of kidneys

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1. Glomerulus:
• Function: filter blood into the first stage of urine formation

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• made up of network of branching and anastomosing glomerular capillaries which are encased in bowman’s capsule

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• Renal tubules:
• Process the glomerular filtrate into urine

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• Proximal convoluted tubule
• Loop of henle: descending and ascending
• Distal convoluted tubule
• Collecting ducts

Blood Supply:

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• Renal artery: Blood from the renal artery is delivered to the afferent arterioles.

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• Afferent arterioles branches to form the glomerular capillaries which come together to form the efferent arterioles.

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• Efferent arterioles divides to form the peritubular capillaries which give rise to the renal vein.

Types of nephron

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• Juxtamedulary nephron:
• The glomerulus is located in the cortex near the corticomedullary junction

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• Has long loop of henle extends deep into the inner medulla.

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• It plays an important role in the production of concentrated urine

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• Cortical or superficial nephron:

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• The glomerulus is located in the outer cortex

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• Has short loop of henle extends only to the outer medulla.

Juxtamedulary nephron

Cortical or superficial nephron

Excreted Urine is product of:

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1. Glomerular Filtration:

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• Glomerular capillaries: are highly permeable to all non-cellular constituents of the plasma but are impermeable to protein and protein bound substances.

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2. Reabsobtion of some filtered substances to the blood

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3. Secretion of some substances from the blood into the renal tubules.

Renal handling of substances

Glomerular Filtration Rate

GFR can be affected by

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• Bowman capsule pressure: an increase of Bowman’s capsule pressure lead to a decrease GFR (kidney Stones)

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• Oncotic pressure: an increase in glomerular Oncotic pressure leads to a decrease in GFR such as:

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• Increase of Plasma osmotic pressure
• Increase of Filtration fraction

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• Capillary hydrostatic pressure

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• Arterial Pressure
• Afferent Resistance
• Efferent Resistance

• Increase afferent arteriolar resistance:

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• Decrease renal blood flow
• Decrease glomerular hydrostatic pressure and decrease GFR

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• Increase efferent arteriolar resistances:

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• decrease renal blood flow
• Initial increase of GFR followed by a decrease

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• increased glomerular hydrostatic leads to an increase in filtration.

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• increased filtration (Increased filtration fraction) allow for an increase in the glomerular oncotic pressure which causes a decrease in filtration

Increased resistance of efferent arterioles also causes an increase of peritubular reabsorption because of

1. Increased oncotic pressure (resulted from the increased filtration fraction)

2. Decrease of peritubular hydrostatic pressure.

Regulation of GFR:

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• Maintain GFR within a normal range despite changes in systemic blood pressure or renal blood flow.

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• Renin-Angiotensin-Aldosterone System:

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• activated by any change in the renal perfusion pressure (such as systemic hypotension)

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• Adjust systemic blood pressure and blood volume.

Angiotensin Converting Enzyme (ACE)

• Tubuloglomerular Feedback: is intrinsic mechanism act to adjust GFR of the same nephrone

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• Juxtaglomerular Apparatus: is special anatomical arrangement of distal tubule and the glomerulus of the same nephron.

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• The macula densa cells is sensitive to the NaCl concentration within the distal tubule.

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• An increase of NaCl concentration activate macula densa cells to signal to the Juxtaglomerular cells of the afferent arterioles to

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• suppress renin release which causes

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• Increases afferent arteriolar resistance
• and decrease glomerular hydrostatic pressure and GFR

Glomerular Filtration Rate

GFR X Ps = Us X V

125 ml/min

C_s : Clearance rate of a substance

P_s : Plasma concentration of substance

U_s : Urine concentration of substance

V : Urine flow rate

Clearance of substance:

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the volume of plasma that is completely cleared of the substance

by the kidney per unit time

Tubular processing of glomerular filtrate.

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• Reabsorption and secretion

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• Only a small fraction of filtered load is secreted by the urine. The majority of filtered substances by the glomeruli is reabsorbed by the renal tubules.

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• Each segment of the renal tubules have a unique structure reflecting their specialized function.

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• Normally

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• 100% of glucose and amino acids are reabsorbed by the proximal tubule

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• 99% of water, sodium are reabsorbed by different segments of renal tubules

Transport: from the lumen of tubule to the blood:

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• Transcellular pathway: required a carrier proteins to transport substances across the apical membrane and then discharged them across the basolateral membrane to the interstitial fluid.

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• Paracellular pathway: substances transported through the tight junction

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• peritubular capillaries: has a high oncotic pressure which enhance the absorption from the interstitial to the peritubular capillaries.

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Proximal tubule:

• extensive brush border of the apical membrane to increase the surface area for transport

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• Abundant mitochondria to support transport of a large variety of substances by both active and passive transport.

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• Reabsorb: 65% of filtered Na, Cl, HCO3, K and 100% of glucose and amino acids

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• Secrets: organic acids, bases and hydrogen ions

• The proximal tubule is permeable to both water and solute and, therefore, the osmolarity of the tubule fluid is similar to that of the blood (isosmotic).

Proximal tubule:

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• reabsorption and secretion is linked to the Na⁺/K⁺ pump.

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• Na⁺/K⁺ pump transports Na⁺ out of the tubular cells through the basolateral membrane which create a low intracellular Na⁺ and a negative intracellular electrical potential.

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• The potential of Na⁺ to diffuse down its electrochemical gradient is used to transport other substances.

Na

Glucose

Amino acids

glucose and amino acid reabsorption

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• facilitated by carrier protein that couple Na⁺ diffusion Na to glucose and amino acids (secondary active transport)

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• Glucose and amino acids then move across the basolateral membrane by facilitated diffusion.

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Water reabsorption:

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• Reabsorption of Na⁺ , HCO^3-, glucose, amino acids and other solutes to the intestinal fluid lead to an increase of the osmotic pressure in the interstitial which causes water to diffuse by osmosis to the blood.

The thin descending loop of henle

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• contain low epithelium with few mitochondria and few membranous folding.

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• This segment is highly Permeable for water but is less permeable for solutes.

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• Because of this ability it is called Concentrating Segment

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• Hyperosmotic

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Thick ascending loop of henle:

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• contain tall epithelium with many mitochondria and membranous infolding to support its high capacity of active transport

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Early distil tubule:

• Retain the same structural characteristic as thick ascending loop of henle.

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• Both segments are highly permeable for solute but less permeable for water.

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• Therefore, those segments are called the diluting segment

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• Hypoosmotic

• K⁺ and Cl⁺ enters the cells from the luminal fluid by co-transport with Na⁺.

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• Cl^- diffuses from the tubular cells through Cl channels on the basolateral membrane.

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• Na⁺/K⁺ pump pump acts to accumulate a high concentration of K⁺ inside cells.

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• K⁺ diffuses out of the cells through the apical and basolateral membranes through K channels.

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• Absorption of Cl^- and secretion of K⁺ make the lumen more positive as compared to the interstitial. This drive the positively charged Ca⁺⁺ and Mg⁺⁺ to move from the lumen to the interstitium.

• Transport of thick limb of henle and early distal tubule is driven by Na⁺/K⁺ pump

Late distal tubule and collecting ducts

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• Principle cells:
• acts to reabsorbed Na⁺ and secret K⁺ through the activity of Na⁺ / K⁺ pump on the basolateral membrane.

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• The high intracellular K⁺ concentration because of Na⁺ / K⁺ pump drives K to diffuse out of the cells into the lumen of the tubule

• Cl^- is absorbed because of the electrical charge created by Na⁺ reabsorption.

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• Intercalated cells: reabsorb K⁺ and secret H by K⁺/H⁺ ATPase pump.

• Permeability of this segment to water is controlled by the concentration of antidiuretic hormone

kidney ability to produce concentrated or diluted urine depends on:

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1.Hypertonic medullary interstitium:

• produced by the countercurrent mechanism which depends on the differential permeability of the thin descending and thick ascending loop of henle to water and solutes.

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• The thick ascending loop:
• actively transport NaCl to the interstitium
• causes an increase of the interstitium osmolarity and reduce the tubule osmolarity.

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• The thin descending loop allows for water to diffuse from the tubular lumen to the interstitium and, thus, raising the osmolarity of the tubule fluid.

2. Antidiuretic hormone:

• different of osmolarity between the fluid of collecting ducts and the interstitium creates a potential for water to move form the tubule to the interstitium.

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• The collecting duct permeability to water depends on the antidiuretic hormone.

Hormonal regulation of tubule processing of filtrate

Role of the kidney in acid-base balance:

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1.Proximal tubule:

• The PH of the proximal tubule is maintained at a level similar to plasma PH

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• Has a high capacity to reabsorb HCO3 and secret H ion.

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• H ion secreted from the proximal tubular cells by the Na/H counter transporter

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• H binds to the filtered HCO3 to form H2O and CO2 under the influence of the carbonic anhydrase enzyme.

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• CO2 then diffuses through the apical membrane to the cells where it binds to H2O to regenerate HCO3.

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• H ion then secreted into the lumen by Na/H counter transport and H-ATPase pump.

• The generated HCO3 is transported to the blood through the basolateral membrane through co-transport with Na or in exchange for Cl.

Apical Membrane

Blood

2.Collecting ducts: determine the final urine pH

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pH of excreted urine is

5.5-7.5 of carnivores

6-9 of ruminants

• Intercalated cells of the collecting ducts acts to secret H⁺ and reabsorb HCO^3-.

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• Carbonic anhydrase catalyze the formation of HCO^3- and H⁺ ion from H₂O and CO₂

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• H⁺ ion secreted through the apical membrane by H⁺ /K⁺ pump and H⁺ -ATPase pump.

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• HCO^3- is transported through the basolateral membrane by Cl^-/ HCO^3- exchanger.

Ureters:

• Move urine from the kidneys to the urinary bladder.

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• The ureters enter the urinary bladder at an oblique angle and this collapses the opening of the ureter and prevent urine backflow to ureter

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Urinary Bladder:

• Collect, store, and release the urine periodically from the body.

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• The urinary bladder has two parts:

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• The sac: is a thick muscular wall lined with many folds of transitional epithelium

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• The neck: contain sphincter of skeletal muscle fibers which provides voluntary control over the process of urination

Urination or micturition

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•  is the release of urine from the urinary bladder through the urethra to the outside of the body.

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• The process is regulated by somatic and the autonomic nervous system. 

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• During storage, bladder pressure stays low, because of the high compliance of the bladder

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• Filling the bladder with urine stimulate the stretch receptors of the bladder wall and activate the maturation reflex which leads to

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• Contraction of the muscles of the bladder wall (detrusor)

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• and relaxation of the sphincter muscles