What is Glomerulonephritis?

Definition: Glomerulonephritis (GN) is an inflammatory condition affecting the glomeruli, the tiny filtering units within the kidneys. These filters are essential for removing waste products, excess fluids, and electrolytes from the blood to produce urine. When the glomeruli become inflamed and scarred, their ability to perform this function deteriorates, leading to a buildup of waste and fluid in the body.

What are the Causes of glomerulonephritis?

1. Infections:
   • Viral Infections: Certain viruses can trigger GN. Notable examples include HIV, hepatitis B, and hepatitis C.
   • Bacterial Infections: Bacteria that cause common throat and skin infections, such as Streptococcus spp or Staphylococcus spp
2. Autoimmune Diseases:
   • Lupus: Systemic lupus erythematosus (SLE) can lead to kidney inflammation as part of a broader autoimmune response.
   • IgA Nephropathy (Berger Disease): This condition involves the buildup of immunoglobulin A (IgA) in the glomeruli, causing inflammation and damage.
3. Genetic Conditions:
   • Alport Syndrome: An inherited disorder that not only causes kidney disease but also affects hearing and vision.
4. Toxins and Medications:
   • Certain drugs or exposure to toxins can damage the glomeruli and trigger GN.

What are the symptoms of glomerulonephtitis?

• Early Symptoms: Often, the kidneys may be significantly damaged before symptoms become apparent. Common early symptoms include:
  • Fatigue: Persistent tiredness that can be a sign of kidney dysfunction.
  • High Blood Pressure: Elevated blood pressure often accompanies GN.
  • Swelling: Accumulation of fluid leading to swelling in the face, hands, feet, and abdomen.
  • Blood and Protein in Urine: Known as hematuria and proteinuria, respectively. These indicators can be detected through urine tests.
• Progressive Symptoms:
  • Decreased Urine Output: Reduced production of urine may signal worsening kidney function.
  • Nausea and Vomiting: These symptoms can occur due to toxin buildup in the body.
  • Fever and Flu-like Symptoms: Systemic inflammation can cause these general symptoms.

How to diagnosis glomerulonephritis?

1. Medical History and Physical Exam: Initial assessment to understand symptoms and possible underlying conditions.
2. Urinalysis: Examines urine for the presence of red and white blood cells, protein, and signs of infection.
3. Blood Tests: Measures levels of waste products like creatinine and urea to evaluate how well the kidneys are filtering blood.
4. Ultrasound: Uses high-frequency sound waves to create images of the kidneys. It helps to assess kidney size, shape, and blood flow, and to identify any abnormalities or blockages.
5. Kidney Biopsy: A definitive diagnostic procedure where a small tissue sample is removed from the kidney and examined under a microscope to detect inflammation, scarring, and other pathological changes.

How to treat glomerulonephritis?

1. Management of Mild Cases:
   • Monitoring: Regular follow-ups to track kidney function and symptoms.
   • Lifestyle Adjustments: Includes dietary changes to reduce salt, protein, and potassium intake.
2. Treatment for Severe Cases:
   • Medications:
     • Blood Pressure Medicines: ACE (angiotensin-converting enzyme) inhibitors help protect kidney function by managing blood pressure.
     • Corticosteroids: These drugs reduce inflammation and prevent scarring of the glomeruli.
     • Diuretics: Help to manage fluid retention by increasing urine production.
   • Dietary Modifications: Limiting protein, sodium, and potassium to reduce kidney strain.
   • Advanced Treatments:
     • Dialysis: An external process that filters blood when the kidneys can no longer perform this function.
     • Kidney Transplant: Replaces the diseased kidney with a healthy kidney from a donor, often considered when kidney function declines to end-stage renal disease (ESRD).

What are the main complications of glomerulonephritis?

• Kidney Failure: Progressive GN can lead to kidney failure, requiring dialysis or a transplant.
• High Blood Pressure: Persistent elevated blood pressure may develop or worsen.
• High Cholesterol: Elevated cholesterol levels are common in chronic kidney conditions.
• Blood Clots: Increased risk of clots such as deep vein thrombosis (DVT) or pulmonary embolism.
• Damage to Other Organs: Prolonged GN can affect other body systems.

When to Contact a Healthcare Provider:

• Seek medical advice if symptoms worsen, new symptoms develop, or if there are concerns about kidney function.

Key Points:

Glomerulonephritis is an inflammatory disease of the kidneys’ filtering units, leading to impaired waste removal and potential complications. Early diagnosis and treatment are crucial for managing symptoms, preventing progression, and addressing potential kidney failure. Regular monitoring and treatment adjustments can significantly impact the management of this condition.

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Excretion:

• It is defined as elimination of metabolic wastes by an organism at exchange boundries such as plasma membrane of unicellular organisms and or excretory tubules (flame cell, nephridia, malphigean tubules, nephrons etc) of multicellular organisms. Metabolic wastes products are nitrogenous materials (urea), CO2, pigments (bilirubin), excess of water, inorganic salts etc. It differ from egestion (defecation) and secretion
• Osmoregulation: It is the process of maintaining constant osmotic conditions in the body. It mainly involve maintaining constant water and electrolyte (Na, K and Cl ion) concentration.

Significance of excretion:

1. Removal of unwanted metabolic byproducts: Metabolism of carbohydrates and fats produces CO2and H2O, similarly Protein metabolism produces nitrogenous wastes in the cell and tissue which are remove by excretion.
2. Removal of toxic wastes: accumulation of excretory products such as nitrogenous wastes, CO2, pigments formed by the breakdown of haemoglobin, drugs etc.is harmful to the body. So, these toxic wastes are removed.
3. Osmoregulation of the body: it helps maintaining constant ionic concentration of body fluid as well as Regulating water content of the body
4. Regulation of body PH
5. Thermoregulation: Excretion also helps to maintain a constant body temperature

Modes and types of excretory wastes in different animals

Excretory products and their types

• Metabolism of carbohydrates and fats produces CO2and H2O which are easy to remove. They are effectively removed through lungs (expired air), skin (sweat) or kidneys (urine).
• Other excretory products such as bile pigments (formed by the breakdown of RBCs), drugs etc. are removed in liver.
• Metabolism of proteins produces nitrogenous wastes such as ammonia, which is the basic nitrogenous catabolites of protein, formed by breakdown of amino acids is finally removed from Kidney.
• Depending upon the form in which nitrogenous waste is excreted from the body, the organisms are grouped as under into three categories:

Ammonotelic, Uricotelic and Ureotelic

1. Amminotelic organism

• Those animals which excrete their nitrogenous waste in the form of ammonia are known as ammonotelic.
• Ammonia is highly soluble in water with which it forms ammonium hydroxide (NH4OH) which can damage cells directly by its alkaline caustic action.
• Excretion of ammonia requires large amounts of water, so that more water loss from the body. That is why such a mode is suitable for aquatic organisms which have a constant access to water.
• Ammonia is the first metabolic waste product of protein metabolism and no energy is required to produce ammonia.
• Examples: All aquatic invertebrates, bony fishes and aquatic amphibians are amminotelic organisms.

2. Uricotelic organism

• Those animals which excrete their nitrogenous waste mainly in the form of uric acid and urates are known as uricotelic.
• The phenomenon is known as uricotelism.
• Elimination of uric acid requires lesser amount of water, comparatively less soluble in water and is less toxic as compared to ammonia.
• Examples: All terrestrial animals like insects, reptiles, and birds excrete uric acid as nitrogenious wastes

3. Ureotelic organism

• Those animals that excrete their nitrogenous waste mainly in the form of urea are known as ureotelic and the phenomenon is known as ureotelism.
• Urea can be stored in body for considerable periods of time, and is least toxic. It is eliminated in the form of urine.
• Examples: Ureotelism is exhibited by semi-terrestrial animals, e.g. adult amphibians and mammals

Excretion in Animals; significance of excretion, modes and types of excretory wastes in different animals

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1. ADH (Anti-diuretic Hormone)

• Antidiuretic hormone (ADH) has the primary role in osmoregulation by controlling the amount of urine formation.
• ADH is also known as Vasopressin
• Body maintain water and electrolytes concentration at a relatively constant level by the mechanism of osmoregulation. Hormone are important signaling molecules that control the regulatory process.
• ADH is synthesized in hypothalamus and secreted by posterior pituitary gland.

• When blood become more concentrated in certain situation such as- Too little amount of water intake, Excessive loss of water by sweating or Consumption of large amount of salt. These conditions are responsible for raised in plasma solute concentration (rise in negative osmotic pressure) ie. Decrease in blood volume.
• The osmo-receptor of Hypothalmus detect increase in plasma solute concentration and signal posterior pituitary gland to release ADH.
• ADH travel to the kidney via the blood as chemical messengers.
• ADH regulates water reabsorption by increasing the permeability of distal convoluted tubules and collecting ducts to water by opening water channel. Water channel are protein, which is synthesized by Golgi complex.
• Binding of ADH on specific cell surface receptor present in DCT and collecting ducts bring water channel to the surface of membrane. Through water channel, water enter from glomerular filtrate to the blood capillary, so that the volume of urine become less and hypertonic. This phenomenon is known as Anti-diuresis.
• When intake of water is high, the process reversed.  Release of ADH is inhibited, so the wall of DCT and collecting duct become impermeable to water causing large volume and hypotonic urine production.  The phenomenon is known as Diuresis.
• Function: ADH increases the reabsorption of water by the distal tubule and collecting duct

Feedback regulation of ADH

Hypothalamus control ADH production by negative feedback mechanism

1.  stimulates ADH synthesis, if osmotic concentration of extracellular fluid is high; urine-concentrated
2.  reduces ADH synthesis, if osmotic concentration of extra cellular fluid and plasma falls; urine-dilutes

Deficiencies of ADH

• Deficiency of ADH or non-functional ADH production causes a clinical disease called Diabetes insipidus. The clinical sign is output of large volume of urine frequently which is due to inadequately reabsorption of water by DCT and the collecting duct. Thrust is the symptoms of the disease.

2. Renin-Angiotensin system

• Renin is an enzyme secreted by juxtaglomerular apparatus that catalyze the conversion of angiotensinogen into active angiotensin hormone.
• When Na+ level decrease in blood. It causes decreased in blood volume and interstitial fluid level because less amount of water enter the blood by osmosis. This result in decreased blood pressure and trigger RAAS.
• The decrease in blood pressure stimulates the group of sensory cells present in the area where the renal tubule (DCT) links up with the afferent and efferent arterioles known as Juxtaglomerular apparatus.
• The cells of the juxtaglomerular apparatus release the enzyme Renin. Renin converts angiotensinogen into angiotensin I.
• Angiotensin converting enzyme (ACE) then converts angiotensin I into angiotensin-II;a peptide hormone that is the active form.

Function:

• Angiotensin-II Stimulates sodium reabsorption by the proximal convoluted tubules. Retaining Na+, raises the osmotic pressure of the blood and reduces water loss from renal tubules
• Raises blood pressure directly by constricting blood vessels

3. Aldosterone hormone

• Aldosterone is a hormone secreted by the outer cortical layer of the adrenal gland.
• Angiotensin II Increases the synthesis and release of aldosterone.
• Aldosterone stimulate Na-K pump, so that more Na+ from the filtrate is reabsorbed by the epithelial cells of the collecting ducts.
• Aldosterone also stimulate sodium absorption from gut and decrease loss of sodium from sweat. Thus, level of Na+ increases in blood, this in turn causes more water absorption raising the volume and blood pressure

Function: Maintain constant plasma Na+ level and also help water reabsorption

References

1. https://en.wikipedia.org/wiki/Renin%E2%80%93angiotensin_system
2. http://www.tutorvista.com/content/biology/biology-iv/excretion/role-kidney-osmoregulation.php
3. http://study.com/academy/lesson/renin-angiotensin-aldosterone-system-raas-pathway-functions-terms.html
4. http://www.people.vcu.edu/~elmiles/hormones/KidneyHormones_print.html
5. http://www.nbs.csudh.edu/chemistry/faculty/nsturm/CHE452/22_RenAngioAldoANP18.htm
6. https://www.boundless.com/biology/textbooks/boundless-biology-textbook/osmotic-regulation-and-the-excretory-system-41/hormonal-control-of-osmoregulatory-functions-232/other-hormonal-controls-for-osmoregulation-868-12115/
7. https://bio.libretexts.org/TextMaps/Map%3A_General_Biology_(OpenStax)/7%3A_Animal_Structure_and_Function/41%3A_Osmotic_Regulation_and_Excretion/41.5%3A_Hormonal_Control_of_Osmoregulatory_Functions

Role of ADH, Renin-Angiotensin and Aldosterone in Osmoregulation

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There are three stages involved in the process of urine  formation. They are-
1. Glomerular filtration or ultra-filtration

2. Selective reabsorption

3. Tubular secretion

Glomerular filtration

• This takes place through the semipermeable walls of the glomerular capillaries and Bowman’s capsule.
• The afferent arterioles supplying blood to glomerular capsule carries useful as well as harmful substances. The useful substances are glucose, aminoacids, vitamins, hormones, electrolytes, ions etc and the harmful substances are metabolic wastes such as urea, uric acids, creatinine, ions, etc.
• The diameter of efferent arterioles is narrower than afferent arterioles. Due to this difference in diameter of arteries, blood leaving the glomerulus creates the pressure known as hydrostatic pressure.
• The glomerular hydrostatic pressure forces the blood to leaves the glomerulus resulting in filtration of blood. A capillary hydrostatic pressure of about 7.3 kPa (55 mmHg) builds up in the glomerulus. However this pressure is opposed by the osmotic pressure of the blood, provided mainly by plasma proteins, about 4 kPa (30 mmHg), and by filtrate hydrostatic pressure of about 2 kPa (15 mmHg in the glomerular capsule.
• The net filtration pressure is,

Therefore: 55-(30 +15) = 10mmHg.

• By the net filtration pressure of 10mmHg, blood is filtered in the glomerular capsule.
• Water and other small molecules readily pass through the filtration slits but Blood cells, plasma proteins and other large molecules are too large to filter through and therefore remain in the capillaries.
• The filtrate containing large amount of water, glucose, aminoacids, uric acid, urea, electrolytes etc in the glomerular capsule is known as nephric filtrate of glomerular filtrate.
• The volume of filtrate formed by both kidneys each minute is called the glomerular filtration rate (GFR). In a healthy adult the GFR is about 125 mL/min, i.e. 180 litres of filtrate are formed each day by the two kidneys

Selective reabsorption

• As the filtrate passes to the renal tubules, useful substances including some water, electrolytes and organic nutrients such as glucose, aminoacids, vitamins hormones etc are selectively reabsorbed from the filtrate back into the blood in the proximal convoluted tubule.
• Reabsorption of some substance is passive, while some substances are actively transported. Major portion of water is reabsorbed by Osmosis.
• Only 60–70% of filtrate reaches the Henle loop. Much of this, especially water, sodium and chloride, is reabsorbed in the loop, so that only 15–20% of the original filtrate reaches the distal convoluted tubule, More electrolytes are reabsorbed here, especially sodium, so the filtrate entering the collecting ducts is actually quite dilute.
• The main function of the collecting ducts is to reabsorb as much water as the body needs.
• Nutrients such as glucose, amino acids, and vitamins are reabsorbed by active transport. Positive charged ions ions are also reabsorbed by active transport while negative charged ions are reabsorbed most often by passive transport. Water is reabsorbed by osmosis, and small proteins are reabsorbed by pinocytosis.

Tubular secretion

• Tubular secretion takes place from the blood in the peritubular capillaries to the filtrate in the renal tubules and can ensure that wastes such as creatinine or excess H+ or excess K+ ions are actively secreted into the filtrate to be excreted.
• Excess K+ ion is secreted in the tubules and in exchange Na+ ion is reabsorbed otherwise it causes a clinical condition called Hyperkalemia.
• Tubular secretion of hydrogen ions (H+) is very important in maintaining normal blood pH.
• Substances such as , e.g. drugs including penicillin and aspirin, may not be entirely filtered out of the blood because of the short time it remains in the glomerulus. Such substances are cleared by secretion from the peritubular capillaries into the filtrate within the convoluted tubules.
• The tubular filtrate is finally known as urine. Human urine is usually hypertonic.

Composition of human urine

Water – 96%

Urea – 2%

Uric acids, creatinine, pigments- 0.3%

Inorganic salts – 2%

Bad smell is due to Urinoid

Pale yellow color due to urochrome or urobillin (which is a breakdown product of haemoglobin)

Micturation:

• The process of time to time collection and removal of urine from urinary bladder is known as micturition. Collection of more than 300ml of urine in urinary bladder creates pressure on the wall. The pressure stimulates the desire for urination.

References

1. https://opentextbc.ca/anatomyandphysiology/chapter/25-5-physiology-of-urine-formation/
2. https://en.wikibooks.org/wiki/Human_Physiology/The_Urinary_System
3. https://legacy.owensboro.kctcs.edu/gcaplan/anat2/note/APIINotes3%20urinary%20system.htm
4. https://www.visiblebody.com/learn/urinary/urine-creation
5. http://study.com/academy/lesson/the-three-processes-of-urine-formation.html
6. http://www.columbia.edu/itc/hs/medical/humandev/2005/HD13-4s.pdf
7. https://www.boundless.com/physiology/textbooks/boundless-anatomy-and-physiology-textbook/urinary-system-25/physiology-of-the-kidneys-240/overview-of-urine-formation-1171-2197/

Physiology of Urine formation

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• Histologically, each kidney is composed of approximately 1 million of Uriniferous tubules or nephron. Nephron is the structural and functional unit of the kidney.

Figure: Nephron- a functional unit of kidney

Each nephron has two major portions:

1. A Renal corpuscle (Malpighian body)
2. A Renal tubule

1. Renal corpuscles (Malpighian body):

• A renal corpuscle consists of a glomerulus surrounded by a glomerular capsule (Bowman’s capsule).
• The glomerulus is a capillary network that arises from an afferent arteriole and empties into an efferent arteriole. The diameter of the efferent arteriole is smaller than that of the afferent arteriole, which helps maintain a fairly high blood pressure in the glomerulus.
• Bowman’s capsule is double walled cup like structure and it encloses the glomerulus. The wall of glomerulus and the Bowman’s capsule consists of a single layer of flattened epithelial cells.
• Glomerular capsule consists of three layers
  • i) Outer parietal layer consists of squamous epithelium cells with minute pore of 12nm diameter called fenestrations
  • ii) Middle basement membrane which is selectively permiable
  • iii) The inner visceral layer of large nucleated cell called podocytes. Podocytes bears finger like projections known as podocels. The areas between the two podocels is filtration slit underlying basement membrane.

2. Renal tubules:

• The renal tubule continues from Bowman’s capsule and consists of the following parts: proximal convoluted tubule (in the renal cortex), loop of Henle (in the renal medulla), and distal convoluted tubule (in the renal cortex).
  • i) Proximal convoluted tubules (PCT): it is proximal part of renal tubules next to Bowman’s capsule. It is lined with microvilli. Maximum reabsorption of water, glucose, amino acids and electrolytes takes place here.
  • ii) Loop of Henle: It is U shaped middle portion of renal tubules. It is composed of ascending and descending loop. Ascending loop is thick walled and impermeable to water while descending loop is thin walled and permeable to water. Counter current mechanism is crucial role of loop of Henle.
  • iii) Distal convoluted tubules (DCT): It is the distal part of renal tubules that leads to collecting ducts. It is similar in structure and function with PCT.
  • iv) Collecting tubules: It is not a part of nephron rather it is a part of kidney. The distal convoluted tubules from several nephrons empty into a collecting tubule. Several collecting tubules then unite to form a papillary duct that empties urine into a minor calyx and then into major calyx and finally into renal pelvis.

Types of nephron

1. Cortical nephron: 80% of the nephrons are short and located within the cortex.
2. Juxtamedulary nephron: 20% of nephron have long loops of Henle that extend into the medulla.

Nephron-Structural anatomy and types

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Gross Structure

• Kidneys are bean-shaped organs, about 11 cm long, 6 cm wide, 3 cm thick and weigh 150 g. They are embedded in, and held in position by, a mass of adipose tissue.
• Each kidney is enclosed by a thin tough fibrous connective tissue called renal capsule that protects it from infections and injuries. Around the capsule there is a layer of fat (adipose tissue) which is further enclosed by another layer of fibrous membrane known as renal fascia. The bean shaped kidney have outer convex surface and inner concave surface.
• Location: The kidneys lie on the posterior abdominal wall, one on each side of the vertebral column, behind the peritoneum and below the diaphragm.
• Position: It is situated at the level of T12-L3. The right kidney is usually slightly lower than the left, probably because of the considerable space occupied by the liver.

Anatomy of kidney

• Longitudinal section of the kidney shows following parts.

1. Capsule: It is an outermost covering composed of fibrous tissue surrounding the kidney.
2. Cortex: It is a reddish-brown layer of tissue immediately below the capsule and outside the renal It consists of renal corpuscles and convoluted tubules.
3. Medulla: It is the innermost layer, consisting of conical areas called the renal pyramids separated by renal columns. There are 8-18 renal pyramids in each kidney. The apex of each pyramid is called a renal papilla, and each papilla projects into a small depression, called a minor calyx (plural calyces). Several minor calyces unite to form a major calyx. In turn, the major calyces join to form a funnel shaped structure called renal pelvis that collects urine and leads to ureter.

Blood supply to kidney

• The renal artery enters the kidney through the hilum and then branches progressively to form the interlobar arteries arcuate arteries, interlobular arteries, and afferent arterioles, which lead to the glomerular capillaries. The distal ends of the capillaries of each glomerulus combine to form the efferent arteriole, which leads to a second capillary network, the peritubular capillaries, that surrounds the renal tubules called vasa recta. The blood vessels of the venous system progressively form the interlobular vein, arcuate vein, interlobar vein, and renal vein, which leaves the kidney beside the renal artery and ureter.

Functions of Kidney:

1. Endocrine functions: kidney is also an endocrine glands. It secretes enzymes renin, 1, 25-dihydroxycholecalciferol, erythropoietin etc.

• Renin; It is an enzyme secreted by cells of juxtaglomerular apparatus which helps in regulation of blood pressure.
• 1, 25-dihydroxycholecalciferol; it is a biological active form of vitamin D3 found in kidney.
• Erythropoietin; it is essential for RBC formation

2. Osmoregulation: Kidney regulate osmotic pressure in the body by regulating fluids and electrolyte balance
3. Homeostasis: also regulate PH balance
4. Excretion: metabolic wastes of the body are excreted in the form of urea, creatinine, uric acid etc in urine.
5. Excretion of Drugs and toxins
6. Selective reabsorption: glucose, amino acids, water and electrolytes  etc are selectively reabsorbed in the renal tubules
7. Erythropoiesis: helps in RBC formation
8. Blood pressure regulation

References

1. https://www.boundless.com/physiology/textbooks/boundless-anatomy-and-physiology-textbook/urinary-system-25/the-kidneys-239/internal-anatomy-of-the-kidneys-1168-4690/
2. https://opentextbc.ca/anatomyandphysiology/chapter/25-3-gross-anatomy-of-the-kidney/
3. http://www.newhealthadvisor.com/kidney-structure-and-function.html
4. http://www.webmd.com/urinary-incontinence-oab/picture-of-the-kidneys#1
5. https://www.healthpages.org/anatomy-function/kidney/
6. http://www.innerbody.com/image_urinov/dige05-new.html

Kidney-Structure, Anatomy and Function

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