Excretion handwritten notes, Schemes and Mind Maps of Physiology

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EXCRETION

10 MARKS

1. PROCESS OF URINE FORMATION Every day kidney produces 1 – 2 liters of urine. The mechanism of urine formation involves three processes: a) Glomerular filtration b) Tubular reabsorption c) Tubular secretion a) Glomerular filtration:

• Process by which the fluid along with the substances dissolved in it passes from the glomerular capillaries in to the Bowman’s capsule is called glomerular filtration
• Blood cells and plasma proteins are not filtered
• Filtration occurs through filtering membrane which is made up of 3 layers – Fenestrated capillary endothelium, basement membrane & podocytes (epithelial cells of Bowman’s capsule) with filtration slits
• The fluid which gets collected in the capsule is called filtrate
• The amount of filtrate formed per minute (GFR – Glomerular Filtration Rate) is 125ml.
• This is mainly determined by net filtration pressure which depends upon the Starling forces acting across the filtering membrane – Glomerular capillary hydrostatic & colloidal osmotic pressure, Bowman’s capsule hydrostatic pressure b) Tubular reabsorption:
• Passage of water and solutes from the filtered fluid in the kidney tubule into the blood is called tubular reabsorption
• Solutes which are reabsorbed are nutrients (glucose & aminoacids), electrolytes (sodium, potassium & chloride) & ions such as bicarbonates.
• Ihe modes of transport are both passive & active transport mechanisms Reabsorption At Proximal Convoluted Tubule:
• Majority of reabsorption takes place at PCT as the surface area is increased due to presence of brush border microvilli
• 65% of filtered water, sodium, chloride, potassium and other solutes
• 100% of glucose and aminoacids
• Sodium is reabsorbed by secondary active transport along with substances like glucose and aminoacids
• This is followed by osmosis of water into the blood. The reabsorption of water at PCT is called obligatory reabsorption of water
• The reabsorption of water and sodium are exactly proportional. So the fluid which leaves the PCT is isotonic Reabsorption At Loop of Henle:
• Loop of Henle consists of three segments - Descending limb, thin ascending limb & thick ascending limb
• About 20% of filtered sodium and chloride, 15% of filtered water and cations such as K+, Ca2+^ and Mg2+^ are reabsorbed in the Loop of Henle
• In the descending limb , water absorption occurs passively because of hypertonic interstitial fluid in this part
• The thin ascending limb is impermeable to water. Limited passive absorption of sodium and chloride occurs
• Thick ascending limb is impermeable to water. 20% of filtered sodium and chloride and other cations are reabsorbed here by the following mechanisms:

B. Surface area of the membrane : Directly proportional to Kf & GFR

• the normal surface area is about 0.8 m^2
• Contraction of the messangial cells compresses the glomerulus & reduces the area of the membrane C. Permeability of the membrane:
• Glomerular capillaries are 50 times more permeable than capillaries of skeletal muscle.
• Permeability of the membrane is influenced by
• size of the particles filtered
• charge of the particles filtered
• Charge of the pores in the filtering membrane
• Particles below 4 nm size (both negative & positive charged) are filtered easily
• Particles above 8 nm size ( both negative & positive charged) are not filtered
• Particles of 4-8 nm size are filtered with difficulty (Positively charged particles are filtered in this size range where as negatively charged particles are not filtered) Reason : The negative charge of the pores in the filtering membrane repel the negatively charged particles E.g – Albumin which is about 6 nm size is not filtered as it is negatively charged particle

1. Effective Filtration Pressure: It is the net outward pressure which determined by forces acting across the filtering membrane. These forces are called Starling forces. Starling Forces acting across the filtering membrane:
2. Glomerular capillary hydrostatic pressure (PGC) = 45 mmHg (favors filtration)
3. Glomerular capillary osmotic pressure (πGC) = 25 mmHg (oppose filtration)
4. Bowmans capsular hydrostatic pressure (PBS) = 10 mmHg (oppose filtration)
5. Bowmans capsular osmotic pressure (πBS) = 0 (no effect on filtration) EFP = Forces favoring filtration – Forces opposing filtration EFP = PGC + πBS – PBS + πGC = (45+0) – (10 + 25) = 10 mmHg Thus GFR = Kf X EFP = 12.5 X 10 = 125 ml / minute Conditions which alter Starling’s forces: Glomerular Hydrostatic pressure (PGC): i) Change in systemic blood pressure – drectly proportional to PGC ii) Constriction of afferent arteriole^ –^ decreases PGC iii) Constriction of efferent arteriole - increases PGC Glomerular osmotic pressure (πGC): i) Dehydration - increases πGC ii) Malnutrition - decreases πGC

Bowman’s capsular Hydrostatic pressure (PBS): i) Ureteral obstruction – increases PBS ii) Edema of the kiney inside the tight renal capsule – increases PBS C) Renal blood flow:

• directly proportional to GFR. Renal bood flow is influenced by nerves, hormones like catecholamines, angiotensin, dopamine & ANP D) Sympathetic stmulation:
• strong acute sympathetic stimulation → constriction of both afferent and efferent arterioles →decrease in renal blood flow → decrease in GFR

3. COUNTERCURRET MECHANISM OF CONCENTRATING THE URINE Normal osmolarity of urine: 300 mosm/lt Osmolarity of diluted urine: Upto 50mosm/lt Osmolarity of concentrated urine: Upto 1200mosm/lt Requirements for concentrating the urine:

1. ADH
2. Hyperosmolar medullary interstitium Factors contributing to hyperosmolarity of medullary interstitium:
3. Countercurrent system
4. Reabsorption at DCT & CD
5. Urea recirculation 1. Countercurrent system : A system in which the inflow runs in parallel, in opposite direction & in close proximity to the outflow Components of countercurrent system in kidney: a) Loop of Henle (contercurrent multiplier) b) Vasarecta (countercurrent exchanger) Role of Loop of Henle as countercurret multiplier in countercurrent mechanism: To generate osmotic gradient & hyperosmolarity of medullary interstitium Mechanism –

• Diffusion of water out of thin descending limb of LOH (This makes the fluid in the tip of the loop to become more concentrated than the surrounding interstitum)
• Passive reabsorption of solutes from the hypertonic fluid in the tin ascending limb (This helps in multiplication of interstitial osmolarity)
• Active reabsorption of sodium & chloride in the thick ascending limb of Loop of Henle (This helps in building up of a higher interstitial osmolarity)

• Again it is reabsorbed in the medullary collecting duct.
• This recirculation of urea before it is excreted in the urine helps to generate medullary osmotic gradient
• Urea recirculation contributes 40% to hyperosmolarity of medullary interstitium ADH : Increases urea reabsorption (This increases the interstitial osmolarity) Increases water reabsorption (This makes the urine concentrated) Renal blood flow : Slow rate of blood flow through the medulla causes retention of sodium in the medullary interstitium **5 marks & 3 marks

1. SPECIAL FEATURES OF RENAL CIRCULATION a. Renal Blood Flow (RBF):** The normal blood flow to kidney is about 1200 ml. This forms about 25% of cardiac output. Kidney receives the maximum blood flow next to liver. b. Portal circulation: An arteriole is interposed between two capillaries. Glomerulus (capillary tuft) – Efferent arteriole – Peritubular capillary c. High pressure system: The pressure in the glomerular capillaries is 45 mmHg. This is much higher compared to the pressure in the systemic capillaries which is 30 mmHg. This high pressure is the main driving force for glomerular filtration d. Vasa recta: Longest capillaries in the form of hairpins. It runs parallel to LOH of juxtamedullary nephron. It acts as countercurrent exchanger and maintains the osmotic gradient from the cortex towards the inner medulla of kidney e. Autoregulation: The ability of kidney to regulate its own blood flow is called autoregulation. This helps the kidney to maintain the blood flow constant between a systemic pressure of 90 – 220 mmHg. Autoregulation is achieved by myogenic principle and tubuloglomerular feedback mechanism f. Regional blood flow : Cortex receives the maximum blood flow whereas the inner medulla receives the minimum blood flow g. Arterio-venous difference of oxygen is minimal compared to the other organs h. Renal O 2 consumption is high 2. JUXTAGLOMERULAR APPARATUS Juxta Glomerular Apparatus refers to the collection of specialized cells located very near to the glomerulus Components: a) Juxtaglomerular cells b) Macula densa cells c) Mesangial cells Juxtaglomerular cells:

• Modified smooth muscle cells of afferent arteriole
• Secrete renin Macula densa Cells:
• Specialized tubular epithelial cells at DCT
• Act as chemoreceptors ( detect the changes in the concentration of sodium and chloride in tubular fluid)

Messangial cells:

• Supporting cells present around glomerulus
• Contractile in nature Functions of JG Apparatus:

1. JG cells secrete renin that activates Renin- Angiotensin system which takes part in regulation of blood volume and pressure
2. Macula densa cells act as sensor in Tubuloglomerular feedback which takes part in autoregulation of renal blood flow and GFR
3. JG apparatus helps to regulate the volume and osmolarity of ECF
4. It secretes erythropoietin which influences erythropoiesis 3. TUBULOGLOMERULAR FEEDBACK Tubuloglomerular feedback refers to a mechanism which maintains a constant renal blood flow & GFR inspite of the changes in mean arterial pressure. It involves the feedback signals from DCT when there is a change in the concentration of sodium chloride in the tubular fluid Increased renal arterial pressure Decreased renal arterial pressure ↓ ↓ Increased RBF & GFR -- Decreased RBF & GFR + ↓ ↓ Increased NaCl concentration Decreased NaCl concentration In the tubular fluid in the tubular fluid ↓ ↓ Sensed by macula densa cells Sensed by macula densa cells ↓ ↓ Feedback effect Feedback effect (Release of adenosine) (Less release of adenosine) ↓ ↓ Constriction of afferent arteriole Dilation of afferent arteriole

Basis: Can be explained by Laplace Law (Laplace law: P = 2T / R where ‘P’ is the pressure, ‘T’ is the tension in the wall & ‘R’ is the radius of the bladder Explanation: Urine accumulation → increase in tension of the bladder wall, but there is increase in radius of the bladder too (called as plasticity of the smooth muscle). The effects of these two factors get neutralized & the pressure remains same. c) Phase II: Steep rise in intravesicular pressure:

• Starts beyond 400 ml
• Tension of wall increases due to contraction of detrussor muscle, but radius is not increased. So, the pressure increases (20 cm to 40 cm of H 2 O)
• This stimulates voiding sensation (triggering the micturition reflex) 5. ACIDIFICATION OF URINE
• Normally the urine is acidic with a pH range from 4.5 to 6.0.
• Acidification of urine is brought about by H+^ secretion in to the tubular fluid
• H+^ secretion takes place throughout nephron.
• H+^ secreted at PCT & LH is utilized for absorption of HCO 3 -. Does not contribute to acidification of urine.
• H+^ secreted in small amounts in the DCT & CD is responsible for the acidification of urine Mechanism Of H+^ secretion: BLOOD Tubular Epithelial Cell LUMEN H 2 O + CO 2 ↓ H 2 CO 3 HCO 3 -^ HCO 3 -^ H+^ ATP H+^ (In DCT) H+ K+^ K+^ (In CD)

Fate of H+ ion in the lumen:

1. Reaction with HCO 3 - : BLOOD TUBULAR CELL LUMEN H 2 O + CO 2 CO 2 H 2 O H 2 CO 3 H 2 CO 3 HCO 3 -^ HCO 3 -^ H+^ H+^ + HCO 3 - 2. Reaction with Ammonia (NH 3 )

Blood Cell Lumen

Na Na + Cl H+^ + Cl NH 4 Cl NH 3 G

3. Reaction with Na 2 HPO 4 (Titratable acidity) CELL Blood Lumen Na 2 HPO 4 Na + NaHPO 4 H+^ + NaHPO 4 NaH 2 PO 4 CO 2 + H 2 O H 2 CO 3 HCO 3 -^ H + Glutamine NH 3 HCO 3 -^ H+ H 2 CO 3 CO 2 + H 2 O

Alcohol - Inhibits ADH secretion Coffee & Tea - Increase GFR & decrease reabsorption of Na+ Lithium & Democlocycline - ADH antagonists OSMOTIC DIURETIC

1. Carbonic anhydrase inhibitor Acetazolamide Methazolamide PCT Inhibit the enzyme – carbonic anhydrase Inhibit the reabsorption of Na+^ & HCO
2. Loop Diuretic Furosemide (Lasix) Bumetanide Ethacrynic acid Thick Ascending Limb of LH Inhibit the Na+ - K+ - 2Cl- Cotransporte Inhibit the reabsorption of Na+
3. Thiazide Hydrochlorothiazide Chlorothiazide Trichlormethiazide Metolazone Early DCT Inhibit Na+- Cl- symport
4. K+ sparing diuretics Spironolactone Amiloride Triamterene Collecting duct Aldosterone antagonist Block the epithelial Na+ channels 1. CORTICAL & JUXTAMEDULLARY NEPHRON CORTICAL NEPHRON JUXTAMEDULLARY NEPHRON Location of Glomerulus Cortex Near junction of cortex and medulla Number 85% 15% Loop of Henle Short Long Vasarecta Absent Present Fluid flow Faster Slow Major Function Excretion of waste products Concentration of urine by countercurrent system

2. FILTERING MEMBRANE COMPLEX

• Filtration membrane is otherwise called as filtration barrier or glomerulo-capillary membrane
• It is the membrane through which the fluid from the plasma of glomerular capillaries pass in to the Bowman’s Capsule. Components:

1. Capillary endothelium:

• Fenestrated (contains pores of 70-90 nm diameter)
• Freely permeable to water, small solutes & small proteins

1. Basal lamina:

• Union of glomerular capillary basement membrane & Bowman’s capsule basement membrane
• Consists of glycoproteins & mucopolysaccharides
• Prevents filtration of proteins as strong negative charges are associated with proteoglycans in the basal lamina

1. Bowman’s Capsule Visceral Epithelium:

• Formed by special cells called podocytes
• Podocytes have finger like processes called pedicels
• The pedicels interdigitate to cover the basement membrane & they are separated by gaps called filtration slits (25 nm diameter) 3. INNERVATION OF URINARY BLADDER Sympathetic nerve supply (Hypogastric nerve) – T 12 to L 2 Site of supply: Trigone of bladder & internal urethral sphincter Functions: a) Carry pain sensation from bladder b) On stimulation, causes relaxation of bladder & contraction of internal urethral sphincter (called as nerve of filling) Parasympathetic nerve supply (Pelvic nerve) – S 2 , S 3 & S 4 Site of supply: Trigone of bladder & internal urethral sphincter

Mechanism: Diffusion independent of solute reabsorption Reabsorption at DCT & CD: (5% at DCT & 14.7% at CD) Mechanism: Osmosis of water through aquaporins is influenced by the hormone ADH (Anti Diuretic Hormone) secreted from posterior pituitary. This type of water reabsorption at DCT & CD under the influence of ADH is called “ facultative water reabsorption”.

4. PROTEINURIA Presence of protein in urine more than the usual amount (100 mg/dl) is called proteinuria Most common protein found is albumin. So the defect is commonly called albuminuria Cause:

• Usually the proteins are not filtered. As they are negatively charged, they are repelled by negative charges at the pores of glomerular capillary wall
• In cases of renal diseases like nephritis, the negative charges are dissipated.
• The permeability of the glomerulus to protein is increased. Effects:
• Loss of protein from plasma leads to hypoproteinemia
• Hypoproteinemia leads to decreased colloidal osmotic pressure
• Decreased colloidal osmotic pressure → decreased plasma volume & edema Orthostatic proteinuria: Proteinuria in standing position

1. AUTOREGULATION Definition : Ability of the kidneys to regulate their own blood flow inspite of the changes in systemic blood pressure is called autoregulation

• Seen between a pressure range of 90 – 120 mmHg
• Seen even after cutting of renal nerves & in an isolated kidney perfused with isotonic saline Mechanisms: a) Myogenic theory b) Tubuloglomerular feedback Myogenic theory: Increase in blood pressure → stretching of smooth muscle of afferent arteriole → contraction of smooth muscle → vasoconstriction → decrease in blood flow Tubuloglomerular feedback (also called as chloride feedback theory): Mechanism: Increase in blood pressure → Increased renal blood flow → Increased GFR → increased chloride concentration at macula densa → increased absorption of chloride at macula densa → increased absorption of chloride at macula densa → release of adenosine by JG apparatus → constriction of afferent arteriole & contraction of messangial cells → decrease in RBF & GFR Decrease in in blood pressure → Decreased renal blood flow → Decreased GFR → decreased chloride concentration at macula densa Vasoconstrictor mechanism Vasodilator mechanism (production of angiotensin II & activation of (Release of dopamine & NO Sympathetic fibers) Less release of adenosine) (The opposing effect of the above mechanisms maintains the constant blood flow to the kidney)