������Physiology of Kidney, Functional Morphology of Nephron �& �Role of kidney in acid base and electrolyte balance�

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Dr. Amar Chaudhary, ^{DVM, MS}

Assistant Professor

Department of Physiology and Biochemistry

Agriculture and Forestry University,

Rampur, Chitwan, Nepal

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Renal system

• The excretory system also called the renal system
• Group of organs in the body that filters out excess fluid and other substances from the body
• Purpose of the renal system is to
• Eliminate waste & toxin from the body
• Regulate blood volume and pressure
• Controls level of electrolyte and metabolites
• Regulate blood pH
• Metabolic waste product of Body
• Ammonia
• Urea
• Uric acid
• Creatine
• Creatinine
• Hippuric acid

Some Terminology

• Polyurea ↑^ed flow of urine
• Oliguria ↓^ed flow of urine
• Anuria Absence of urine
• Stranguria Slower & painful flow of urine
• Glucosuria Presence of glucose in urine
• Proteinuria Presence of protein in urine
• Natriuria Excess Na⁺ in the urine
• Pyramids Pale conical shaped striations
• Hilum Concave border in where renal artery,

renal vein & ureter enters and leave

Kidney

• Surrounded by fibrous capsule
• Three major region of the kidney
• Renal cortex
• Renal Medulla
• Renal Pelvis
• Urine formed is passes through the renal papillae at the apex of the Pyramid into a minor calyx – Major Calyx – renal Pelvis

Function of kidney

• Kidneys are vital organs responsible for maintaining homeostasis in the body
• Primary functions include filtering blood, removing waste products, regulating fluid and electrolyte balance, and controlling acid-base balance
• Chief function is the formation of urine
• Excretion of
• Metabolic waste products & foreign chemicals
• Drugs, hormone & metabolites - urea, creatinine, uric acid, end products of haemoglobin breakdown and metabolites of various hormones
• Play a significant role in endocrine functions:
• such as erythropoiesis regulation through the release of erythropoietin and the regulation of blood pressure through the renin-angiotensin-aldosterone system (RAAS).
• Gluconeogenesis:
• Kidneys synthesize glucose from amino acids and other precursors during prolonged fasting

Morphology of Nephron

Parts of the Nephron

• Renal Corpuscle:
• Glomerulus:
• A capillary tuft where filtration of blood occurs
• It filters plasma but prevents larger molecules (like proteins) from entering the filtrate
• Filtration Membrane(Glomerular basement membrane)
• Specialized structure envelops capillary loop and continue with basement membrane of B. capsule, Composed of :
• Fenestrated endothelial cells
• Basement membrane, and
• Podocytes (cells with foot processes that prevent larger molecules from passing)
• Bowman’s Capsule:
• Encases the glomerulus (a network of capillaries)
• The space between the capsule and glomerulus is where filtrate is first collected

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Morphology of Nephron

Parts of the Nephron

• Renal Tubule:
• Proximal Convoluted Tubule (PCT):
• Located in the cortex
• It’s responsible for the bulk of reabsorption of water, electrolytes, glucose, and amino acids
• Loop of Henle:
• Has a descending and ascending limb
• Distal Convoluted Tubule (DCT):
• Responsible for electrolyte balance, especially sodium, potassium, and calcium ions
• It responds to hormonal regulation (e.g., aldosterone for sodium reabsorption and potassium secretion)
• Collecting Duct:
• Collects urine from multiple nephrons and plays a major role in water reabsorption and acid-base balance
• The final concentration of urine occurs here

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Types of nephron

Mammalian kidney has two principal types of nephrons

• Cortical nephrons :
• Nephrons with glomeruli in the outer and middle cortices 
• They are associated with the loop of Henle that extend to the junction of the cortex and medulla or into the outer zone of the medulla
• Juxtamedullary nephrons
• Those nephrons with glomeruli in the cortex close to the medulla
• They are associated with loops of Henle that extend more deep into the medulla

Vasa Recta

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• Peritubular capillaries branches to form the vasa recta into the medulla and lie side by side with the loops of Henle.
• Like the loops of Henle, the vasa recta return toward the cortex and empty into the cortical veins.
• They are associated with long looped nephrons.
• They play an essential role in the formation of concentrated urine.

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Bowman’s capsule

• Renal Corpuscles
• The renal corpuscle is the initial part of the nephron, responsible for the filtration of blood.
• It consists of two main structures

Glomerulus

• Structure:
• A network of capillaries located within the Bowman's capsule.
• These capillaries are fenestrated (have pores) and are surrounded by mesangial cells, which help regulate the glomerular filtration rate (GFR)
• Function:
• Filtration: Blood entering the glomerulus through the afferent arteriole is filtered.
• The high hydrostatic pressure forces water and small solutes like glucose, salts, and urea out of the blood into the Bowman's capsule.
• The filtration barrier (composed of fenestrated endothelium, basement membrane, and podocytes) restricts the passage of large molecules such as proteins and blood cells, which do not normally appear in the filtrate.
• The glomerular filtration rate (GFR) is regulated by the constriction and dilation of the afferent and efferent arterioles, and mesangial cell contraction.

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Bowman’s capsule

• Bowman's Capsule (Glomerular Capsule)
• Structure:
• A double-walled, cup-like structure surrounding the glomerulus
• The space between the two layers of the capsule is the capsular space or urinary space
• Function:
• Collects the filtrate that is passed from the glomerulus.
• This filtrate is composed of water, small solutes, and waste products.
• The filtrate then flows into the renal tubule for further processing.

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Renal Tubules

• After the filtration in the renal corpuscle, the filtrate moves through the renal tubules
• The renal tubules consist of the proximal convoluted tubule (PCT), loop of Henle, distal convoluted tubule (DCT), and the collecting duct
• These structures are involved in the reabsorption of essential substances and the secretion of waste products
• Proximal Convoluted Tubule (PCT)
• Structure:
• The PCT is the first section of the renal tubule that follows Bowman's capsule
• It has a highly convoluted structure and a brush border of microvilli on the apical surface, increasing the surface area for reabsorption
• Function:
• Reabsorption: The PCT reabsorbs the majority of the filtered water and solutes back into the bloodstream, including:
• Na+, Cl-, glucose, amino acids, bicarbonate (HCO₃⁻), and phosphate.
• Water: 65-70% of the filtered water is reabsorbed here.
• Secretion: Some substances, such as organic acids and waste products (like uric acid), are secreted into the PCT from the blood.
• Glucose and amino acids are normally completely reabsorbed in the PCT under healthy conditions.
• Bicarbonate is largely reabsorbed to help regulate the blood's p^H.

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Renal Tubules

Loop of Henle

• Structure: The Loop of Henle is a U-shaped structure with a descending limb and an ascending limb
• It extends into the renal medulla, which allows it to create a concentration gradient in the kidney.
• Function:
• Concentration of Urine:
• The descending limb
• is permeable to water but impermeable to salts
• As the filtrate moves down, water is reabsorbed into the surrounding interstitial fluid, concentrating the urine
• The ascending limb
• is impermeable to water but actively transports Na⁺ and Cl⁻ out of the filtrate
• The thick ascending limb
• uses active transport of ions to create a high osmotic gradient in the renal medulla, which is vital for water reabsorption in the collecting ducts
• Osmoregulation:
• The Loop of Henle plays a crucial role in creating a hyperosmotic medullary environment, which enables the kidney to concentrate urine and conserve water.

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Renal Tubules

Distal Convoluted Tubule (DCT)

• Structure:
• The DCT follows the loop of Henle and is shorter and less convoluted than the PCT
• It is located in the cortex of the kidney
• Function:
• Selective Reabsorption and Secretion:
• The DCT plays a key role in regulating the final composition of urine
• Na⁺ reabsorption: Under the influence of aldosterone, Na⁺ is reabsorbed from the filtrate into the blood
• K⁺ secretion: The DCT also secretes K⁺ into the filtrate, a process regulated by aldosterone
• Ca²⁺ reabsorption: Calcium reabsorption is regulated by parathyroid hormone (PTH)
• pH regulation: The DCT helps in maintaining acid-base balance by secreting H⁺ and reabsorbing HCO₃⁻.

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Renal Tubules

Collecting Duct

• Structure:
• The collecting duct is the final segment of the nephron
• Multiple nephrons drain into each collecting duct
• The ducts travel through the renal medulla towards the renal pelvis
• Function:
• Water Reabsorption:
• The collecting duct is permeable to water under the influence of antidiuretic hormone (ADH), which regulates the water balance
• When ADH is present, water is reabsorbed, making the urine more concentrated
• Urea Recycling:
• Urea is reabsorbed in the inner medullary collecting ducts, contributing to the creation of the osmotic gradient in the kidney
• Final Urine Composition:
• The final composition of urine (water, salts, urea, and waste products) is determined by processes in the collecting ducts
• The ability of the collecting ducts to adjust water permeability under the influence of ADH is critical for maintaining body fluid homeostasis.

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Blood Supplies to kidney

Role of kidney in Acid- base Balance

A. 1st line: Blood buffer system (Re-adjust P^H within seconds)

• Bicarbonate buffer system
• Phosphate buffer system
• Protein buffer system

B. 2nd line: Respiratory mechanism (Re-adjust within minutes)

• By removal of Carbon dioxide ( Hyperventillation)

C. Renal mechanism (takes few hours to days to adjust PH)

• Kidney regulate the acid base balance by the four major renal mechanisms
• Excretion of Hydrogen ion concentration (H⁺)
• Reabsorption of Bicarbonates (HCO3^-)
• Excretion of Titratable acid
• Excretion of NH4⁺ (Ammonium ions)

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Kidneys role in Acid –Base balance

• Kidneys play a crucial role in maintaining the body’s acid-base balance by regulating the excretion of hydrogen ions (H⁺) and the reabsorption of bicarbonate ions (HCO₃⁻)
• Reabsorption of Bicarbonate:
• In the PCT, most bicarbonate (HCO₃⁻) is reabsorbed
• Carbonic anhydrase in the tubular cells helps convert CO₂ and H₂O into H₂CO₃ (carbonic acid), which dissociates into H⁺ and HCO₃⁻.
• The H⁺ is secreted into the filtrate, while HCO₃⁻ is reabsorbed into the blood.

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Kidneys role in Acid –Base balance

• Excretion of Hydrogen Ions (H⁺):
• In the DCT and collecting ducts, H⁺ is actively secreted into the filtrate in exchange for sodium (Na⁺) or potassium (K⁺) ions.
• This process helps to lower the blood's acid levels, maintaining the blood pH within the normal range (7.35-7.45).

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Kidneys role in Acid –Base balance

• Ammonium (NH₄⁺) Secretion:
• The kidneys also secrete ammonium (NH₄⁺) as a buffer for excess acid
• Ammonia (NH₃) is generated in the proximal tubule from glutamine metabolism
• Ammonia binds with H⁺ to form ammonium (NH₄⁺), which is then excreted in the urine, helping to reduce the body's acid load

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Kidneys role in Acid –Base balance

• Phosphate Buffers:
• In addition to ammonia, phosphate buffers are used in the renal tubules to help buffer excess hydrogen ions (H⁺) in the filtrate

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Kidney's Role in Electrolyte Balance

• kidneys regulate various electrolytes, which are essential for normal cell function, nerve transmission, muscle contraction, and fluid balance
• Sodium (Na⁺):
• Sodium is primarily reabsorbed in the PCT, thick ascending loop of Henle, and DCT
• Aldosterone, a hormone secreted by the adrenal glands, promotes sodium reabsorption in the collecting ducts by increasing the activity of Na⁺/K⁺ ATPase pumps
• Potassium (K⁺):
• Potassium is filtered at the glomerulus and largely reabsorbed in the PCT and thick ascending loop of Henle
• In the DCT and collecting duct, potassium secretion into the urine is regulated by aldosterone. High potassium levels stimulate aldosterone release, which increases potassium secretion
• Calcium (Ca²⁺):
• Calcium is primarily reabsorbed in the PCT and loop of Henle.
• The DCT also fine-tunes calcium reabsorption, which is regulated by parathyroid hormone (PTH)
• PTH increases calcium reabsorption in the kidneys when blood calcium levels are low.
• Phosphate (PO₄³⁻):
• Phosphate is filtered and reabsorbed in the PCT
• The reabsorption of phosphate is influenced by PTH, which decreases phosphate reabsorption, leading to phosphate excretion in the urine when blood phosphate levels are high

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Regulation of kidney function(Feedback mechanism)

1. Renin-Angiotensin-Aldosterone System (RAAS):
1. Renin is released by juxtaglomerular cells in response to low blood pressure or sodium levels. Renin converts angiotensinogen (from the liver) into angiotensin I, which is then converted to angiotensin II by ACE (angiotensin-converting enzyme) in the lungs.
2. Angiotensin II raises blood pressure by constricting blood vessels and stimulating aldosterone release from the adrenal glands.
3. Aldosterone increases sodium reabsorption in the DCT and collecting ducts, helping to raise blood pressure and restore sodium balance.
2. Antidiuretic Hormone (ADH):
• ADH (also called vasopressin) is released by the posterior pituitary in response to increased plasma osmolality or low blood volume.
• It increases water reabsorption in the collecting ducts by promoting the insertion of aquaporin channels into the tubular cells, which allows water to pass from the filtrate into the bloodstream.
3. Parathyroid Hormone (PTH):
• PTH is released from the parathyroid glands in response to low blood calcium levels. It increases calcium reabsorption in the kidneys and stimulates the conversion of vitamin D to its active form, enhancing calcium absorption in the intestines.