Download MBBS 1st Year Physiology Renal Physiology Notes Notes

Endocrine Functions of Kidney:

Hormones Secreted by Kidney are:

1. Erythropoietin - RBC product

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2. Thrombopoietin
3. Renin - TBP
4. Calcitriol (1,2,5-dihydroxycholecalciferol)
5. Prostaglandins - Inflammation

Types of Nephrons:

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Juxtaglomerular Apparatus:

Juxtaglomerular apparatus is a specialized organ situated near the glomerulus of each nephron.

Structure of JGA: JGA is formed by 3 different structures:

1. Macula densa
2. Extraglomerular mesangial cells (Lacis cells)

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3. Juxtaglomerular cells (Granular cells)

Macula Densa:

• End portion of thick ascending segment of Henle before it opens into DCT.
• Adjacent to afferent & efferent arteriole of same nephron.
• Very close to afferent arteriole.

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• Formed by tightly packed cuboidal epithelial cells.
• Sensitive to NaCl in tubular fluid.

Intraglomerular Mesangial Cells:

• Another type of mesangial cells that are in glomerular capillaries called glomerular mesangial cells.
• Support glomerular capillary loops by surrounding the capillaries in the form of a cellular network.

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Function:

1. Regulate glomerular filtration by contractile property.
2. Phagocytic
3. Secrete glomerular matrix (cytokines)

Granular Cells (Juxtaglomerular Cells):

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• Specialized smooth muscle cells.
• In the wall of afferent arteriole just before it enters the Bowman's capsule.
• These smooth muscle cells are mostly in tunica media & tunica adventitia on the wall of afferent arteriole.
• Called granular cells: full of secretory granules in their cytoplasm (renin).

Functions of JGA:

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1. Hormone secretion.
2. Regulates glomerular blood flow & GFR.

JGA secretes 2 hormones:

1. Renin
2. Ply - secreted by Lacis cells/extraglomerular mesangial cells of JGA. Also secreted by interstitial cells of Medulla called Type I Medullary interstitial cells.

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Renin:

1. Arterial BP
2. ECF volume
3. Sympathetic stimulation
4. Plasma Na+ & Cl-

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Filtration Fraction:

• Fraction/portion of renal plasma, which will be the filtrate.
• It is the ratio of GFR & Renal plasma flow.
• It is expressed in %.

FF = (GFR / Renal plasma flow) * 100

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Normal filtration fraction = 15-20%

Factors Affecting GFR:

1. Renal blood flow (most important factor)
   • GFR & renal blood flow
   • Normal blood flow to kidney - 300ml/min

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Regulation of Renal Blood Flow:

• Autoregulation: intrinsic ability as an organ to regulate its blood flow.
• Autoregulation is not in some vital organs - heart, brain, kidney.

Renal Autoregulation: Aim to maintain GFR.

Renal blood flow remains normal even when the BP varies up to 60-180 mmHg.

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Mechanisms of Autoregulation:

1. Myogenic Response:
   • Increased blood flow to kidney
   • Elastic wall of afferent arteriole stretched
   • Influx of Ca++ from ECF into cells
   • Contraction of smooth muscle of afferent arteriole

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   • Constriction of afferent arteriole
   • Decreased blood flow
2. Tubuloglomerular Feedback:
   • Mechanism to regulate GFR through renal tubule & macula densa.
   • JGA is sensitive to NaCl in tubular fluid.

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Regulation of Glomerulotubular Balance:

• Filtration & reabsorption balance H2O, water & solutes in kidney.

GFR increases, solutes tubular load of PCT & water in PCT increases. There is reabsorption of solutes & water from renal tubules.

Mechanism of Glomerulotubular Balance occurs if osmotic pressure in peritubular capillaries. Amount of plasma protein accumulates in peritubular capillaries & water. Increased osmotic pressure in peritubular capillaries. Increased reabsorption of Na+ & H2O from tubules into capillary blood. GFR decreases.

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Reabsorption of Important Substances:

1. Reabsorption of Na+:
   • From the glomerular filtrate, 99% of Na+ is reabsorbed.
   • 2/3rd of Na+ is reabsorbed in PCT.
   • Remaining 1/3rd reabsorbed in other segments (except descending limb) & collecting duct.

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Na+ Reabsorption occurs in steps:

1. Transport from the lumen of renal tubules into tubular epithelial cells:
   • Active transport - occurring in ways:
     1. Antiport - in exchange for H+ into PCT.
     2. Symport - Na+ cotransport along with other solutes like AA, glucose in other segments & collecting duct.
   • Some amount of Na+ diffuses from lumen into tubular epithelial cells due to electrochemical gradient. Developed by Na-K pump.

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   • Transport from tubular epithelial cells into interstitial fluid: By Na+-K+ pump.
   • Transport from interstitial fluid into blood: By concentration gradient.
   • In DCT - reabsorption of Na+ & H2O. Aldosterone - adrenal cortex. Excretion of K+.

Reabsorption of Water:

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• From PCT & Collecting duct.
• Reabsorption of water from PCT - Obligatory reabsorption.
• Reabsorption of H2O from PCT is secondary (consequent) to Na+.
• Na+ reabsorbed from PCT. Osmosis of H2O from renal tubules.
• Reabsorption of water from DCT & collecting duct. Facultative water reabsorption - occurs by the activity of ADH.

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• Normally, DCT & PCT impermeable to H2O. ADH - permeable to H2O.
• ADH combines with vasopressin (V2) receptor in tubular epithelial membrane.

Reabsorption of Glucose:

• Glucose - completely reabsorbed by PCT.
• Transported by 20 active transport Na cotransport mechanism.

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Tubular Maximum for Glucose (TmG):

• Adult - 375 mg/min
• 300 mg/min

Renal Threshold for Glucose:

• 180 mg/dl in venous blood

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• When blood level reaches 180 mg/dl, glucose is not completely reabsorbed. Appears in urine - Glycosuria.

Concentration of Urine:

• When water content in the body decreases, kidney retains Na+ & excretes concentrated urine.

Processes:

1. Development & maintenance of medullary gradient by countercurrent mechanism.

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2. Secretion of ADH - facultative H2O reabsorption.

Medullary Gradient:

• Cortical interstitial fluid is isotonic to plasma with osmolarity 300 mOsm/L.
• Osmolarity increases gradually from cortex part towards inner medulla.
• Osmolarity is maximum at the innermost part of medulla near renal sinus. It is hypertonic with osmolarity of 1200 mOsmol/L.

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• This type of increase in osmolarity of medullary interstitial fluid is called medullary gradient.

Loop of Henle: Functional responsible for hyperosmolarity of medulla (medullary gradient).

• Role of Loop of Henle is development of juxtamedullary nephrons.
• Functions as countercurrent multiplier.
• Loop of these nephrons is long & veins deep into the medulla.

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Main Reason for Hyperosmolarity of Medullary Interstitium:

• Active reabsorption of NaCl (solute) at thick ascending limb of Loop of Henle into medullary interstitium.
• Solutes accumulate in medullary interstitium.
• Now, due to concentration gradient, NaCl diffuses from ascending limb into the descending limb of LoH.
• NaCl & H2O - repeatedly recirculated into ascending limb & descending limb through medullary interstitial fluid, leaving small portion to be excreted into urine.

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Apart from this, there is regular addition of NaCl into descending limb by constant filtration.

Reabsorption of NaCl from ascending limb. Addition of new NaCl ions into descending limb.

Increase/multiply the osmolarity of medullary interstitial fluid & medullary gradient.

Other Factors Responsible for Hyperosmolarity of Medulla:

1. Reabsorption of Na+ from collecting duct.

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2. Recirculation of urea.

Countercurrent Exchanger:

• Vasa recta function as: It is responsible for maintenance of medullary gradient which is developed by countercurrent multiplier.

Role of Vasa Recta in the maintenance of Hyperosmolarity:

• Acts like counter current exchanger because of its position.

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• It is 'U' shaped tubule with descending limb - runs along descending limb of LoH. Ascending limb - runs along ascending limb of LoH.

When blood passes through ascending limb of vasa recta, NaCl diffuses out of ascending blood & enters interstitial fluid of medulla & water diffuses into blood.

Vasa Recta retain NaCl in medullary interstitium & removes H2O from it. Hyperosmolarity is maintained.

• Recycling of urea also occurs through vasa recta.
• Along with NaCl, some urea also enters descending limb of vasa recta.

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• Blood passes to ascending limb of vasa recta.
• Urea diffuses back to medullary interstitium along with NaCl.
• NaCl & urea are exchanged for water. Ascending & descending limb of vasa recta. This system is called countercurrent exchanger.

• Polyuria: Increased urinary output with frequent voiding.
• ADH deficiency.

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• Common in diabetes insipidus.
• Renal tubules fail to reabsorb water.

Role of Kidney in Acid-Base Balance:

Kidney prevents metabolic acidosis by ways:

1. Reabsorption of NWS.

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2. Secretion of H+.

Reabsorption of HWS: 4320 mEq of NWS is filtered everyday by the glomerulus. It is called Filtered load of HOS.

Excretion of this much HOS in urine will affect acid-base balance in our body. So, HOS must be taken from renal tubules by reabsorption.

Us Secretion of H+:

1. Reabsorption of almost all HOS above occurs by the reabsorption of H+ by renal tubules.

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2. 4380 mEq of H+ appears everyday in renal tubules by filtration.
3. Most of them is utilized for NWS reabsorption. Only 50-100 mEq is excreted. Results in acidification of urine.

Secretion of H+ into renal tubules occurs by the lumen into PCT/DCT/CD. Reabsorption of NaCO3 by pumps - Na+-H+ transport pump. Proton pump.

Excrete/Removal of H+ & Acidification of Urine:

By mechanisms:

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1. NWS mechanism.
2. NH3 mechanism.
3. PO4 mechanism.

Bicarbonate Mechanism - mainly PCT

For every H+ secreted into lumen of tubule, 1 NWS is reabsorbed from tubule. In this way kidney conserve NWS.

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Reabsorption of HWS - important factor for maintaining pH of body fluids.

Composition of Urine:

• Water

Organic Substances:

1. Urea

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2. Uric acid
3. Ureanine
4. NH3

Inorganic Substances:

1. Na+

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2. K+
3. Ca++
4. Cl-
5. PO43-
6. SO42-

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Renal Function Tests:

Group of tests that are performed to assess the function of kidney.

Types:

1. Exam of urine alone.
2. Examination of blood alone.

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3. Examination of urine & blood.

Examination of Urine - Urinalysis:

Routine examination of urine/urinalysis is a group of diagnostic tests performed on the sample of urine.

Urinalysis is done by:

1. Physical examination - volume, color, appearance.

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2. Microscopic examination.
3. Chemical analysis - to analyze abnormal constituents in urine like glucose, protein, bile salt, blood, ketone bodies.

Examination of Blood During:

Measurement of GFR: A substance that is completely filtered but neither reabsorbed nor secreted should be used to measure GFR.

Inulin - ideal substance used to measure GFR. Neither reabsorbed nor secreted. Completely filtered. Inulin indicates GFR.

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Inulin Clearance:

Known amount of Inulin injected into body. After sometime, [Inulin] in urine, volume of urine excreted.

GFR = (Inulin in urine * volume of urine output) / [Inulin] plasma

Creatinine Clearance:

Used to measure GFR. Easier than inulin clearance. Creatinine is already there in the body fluids & its plasma concentration is steady throughout the day.

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Creatinine is completely filtered & being a metabolite, it is neither secreted nor reabsorbed.

The normal value of GFR determined by creatinine clearance = value of GFR determined by inulin clearance.

Measurement of Renal Plasma Flow:

To measure renal plasma flow, a substance which is filtered & secreted but not reabsorbed is used.

Ex: P-aminohippuric acid (PAH)

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PAH clearance indicates the amount of plasma that passes through kidney.

A known volume of PAH injected into body. After sometime, [PAH] in urine, volume of urine excreted.

Renal plasma flow = ([PAH] urine * volume of urine output) / [PAH] plasma

Urea Clearance Test:

Clinical test to assess the clearance of urea from plasma by kidney per minute.

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Test Requires:

1. Blood sample to determine urea level in blood.
2. Urine samples collected at 1 hour interval to determine the urea cleared by kidney into urine.

Normal value of urea clearance: 70ml/min

Urea: Waste product formed during protein metabolism. Excreted into urine.

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Determination of urea clearance forms a specific test to assess kidney/renal function.

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