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(5) Renal (Facts (Determinants (ICF: Potassium, ECF (Interstitial): Sodium…
(5) Renal
Facts
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Kidney Function
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Hormone Production: Renin (BP), Calcitriol (Calcium&Phosphate), Erthropoietin (RBC Production)
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Normal urine contains very small amounts of RBCs, WBCs, albumins and globulins. Water 99%, Sodium 99.5%, Glucose 100%, Urea 44%
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Osmolality: Mass Osmolarity: Volume
Wide Range of Osmolality: 50-1400 mOsm/kg
Normal Serum: 275–295 mosm/kg
ADH: Regulates H2O in response to ECF Osmolality (Also causes thirst) sensed by osmoreceptors near hypothalamus
- Angiotensin II triggers ADH
Aldosterone: Regulates Na in response to ECF Volume sensed by Macula Densa
- ECF osmolarity increases:
- Trigger thirst sensation
- Trigger creation of concentrated urine
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Anatomy
Na Resorption
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3) DCT
- Active
- Aldosterone mediated
2) LoH
- Passive: Dec + Thin Asc
- Active: Thick Asc
1) PCT
- Active: Na/K Antiport
- Active: Na/Glucose Symport
- Passive: H2O & Solute
Medullary Osmotic Gradient
Maintained
Countercurrent Exchange in Vasa Recta
- Removes excess water & solute
- Maintain osmotic gradient
- Slower blood flow, more efficient
- Provides nutrients for ATP
Established
Urea Recycling
- Cortical CD ADH inc H2O perme but not Urea
- Medullary CD ADH inc H2O perma & Urea transporter
Countercurrent Multiplication
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Single Effect (Equilibration step):
- Asc LoH Thick active transport out NaCl
- Dsc LoH H2O diffuse out into interstitial
Tubular cells
Transport Mechanisms
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Secondary Active Transport
- Energy from another solute
- Not directly from ATP
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Types of Nephron
Juxtamedullary Nephron
- 20-30% of nephrons
- More efficient + develope osmotic gradient
- Longer loop of henle
- Corpuscle closer to the medulla
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Nephrotic Segments
Thin Ascending LoH (Passive)
- Impermeable to water, permeable to solutes
- Solutes diffuse out
Medullary Collecting duct
- Reabsob H2O & Salt
- Urea Passively Reabsorbed
- ADH controls H2O permeability + Inc transporter for Urea
- Acid-base balance
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Distal convoluted T (Passive)
- Determines volume of urine (together w CT)
- Normally impermeable to water
- Reabsorb 5% H2O & Na
- Aldosterone: Reabsorb Na, Secrete K
- ADH controls H2O permeability
Thick ascending LoH (Active)
- Impermeable to water, permeable to solutes
- Na/K Primary (antiport) Na into ECF
- Na, K, Cl across apical membrane
- Filtrate in before DCT more dilute
Thin descending LoH (Passive)
- Highly permeable to water
- Moderately permeable to urea
- Reabsorb 20% of Na, Cl
- Reabsorb 10% of H2O
Water diffuse out, Solutes diffuse in
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Proximal convoluted T (Active)
- Reabsorb 2/3 of filtered (H2O, Na, Cl)
- Reabsorb all organic molecules (Glucose, AA) by Secondary AT
- Reabsorb ions (K+, Po4, Ca++, HCO3-)
- Na/K Primary (Antiport) Na into ECF
- Concentration gradient from Na/K allows symport & ions Secondary AT
- DIffuse/symport across basolateral membrane
- H2O by osmosis
- Filtrate in PCT have same osmolarity as surroundings
Glomerulus
- Greatest mass of excreted substances
- Fenestrated Capillary Endothelium
- Basal Lamina / Basement Membrane + Podocytes
- Bowman's capsule epithelium
Macula Densa 2 responses to low NaCl
(1) Vasodilate afferent
(2) Release renin form juxtaglomarular cells
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Hurmoral
ADH
3) Inc Sodium Absorption across Asc LoH
- Contributes to countercurrent multiplication in ddistal tubule and collecting duct
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2) Inc Urea permeability Medullary Collecting Duct
- Urea enters by following water
- Moves down conc gradient
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Potassium Balance
Regulation
Chronic Response:
- Aldosterone secretion
- Colonic secretion
Acute Response: ECF into ICF
- Insulin/Catecholamines
- Acid-Base alkalolsis (K+ in)
- Inc ECF Osmolality, K+ efflux (no one knows but in diabetes)
Function:
- Maintenance of intracellular volume
- Resting Membrane Potential
- Cellular processes
- BP, vascular tone
Pathophysiology
Hypokalemia
- Renal losses
- Diarrhea / Vomiting
- Insulin / Thyrotoxicosis
Hyperkalemia
- Renal retention / failure
- Tissue breakdown
- Causes cardiac arrest
Renal handling:
- Resorption at PCT, Thick A LoH, early DCT (Unregulated)
- Secretion at DCT & Cortical CT (Regulated)
- Reabsorption by both Principal & Intercalated cells
- Secretion by Principal cells
Regulation
Regulation of RBF
- Hemorrhage activate Humoral & Neural
- Whenever there is dilation, increases RBF
Humoral factors
Vasodilate
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Atrial natiuretic peptide (ANP)
- **Reduces expanded ECF
- Secreted by cardiac muscle **cells
- Constriction (Efferent) Dilate (Afferent)
Prostaglandins
- Produced in kidney
- Modulate vasoconstriction by Sympathetic NS & angiotensin II
Vasoconstrict
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Angiotensin II
- Low Conc: Constriction of Efferent
- High Conc: Both Afferent & Efferent
RAAS (Renin-Angiotensin-Aldosterone System)
- Low BP / Low serum Sodium
- Angiotensinogen (Liver)
- Renin (Granular JGA)
- Ang + Renin = Ang I
- Ang I + ACE = Ang II (Lungs)
Ang II works on
- Constrict arterioles Kidney
- Aldosterone Adrenal Glands
- ADH production Brain
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Ang II on Kidney
- Vasoconstriction in arterioles
- Low Conc: Constriction of Efferent
- High Conc: Both Afferent & Efferent but Efferent more*
Inc BP
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Constricted efferent, lower peritubular capillary hydrostatic pressure (Inc Na+ and H2O resorption)
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Autoregulation of RBF and GFR
- Using intra-renal mechanisms
- Mean arterial 80-180mmHg
- eg. Hypotension (acute renal failure)
- eg. Hypertension (damage kidney)
Tubulo-glomerular feedback
- Eg High GFR Macula densa of JGA sense NaCl
- (1) Regulation of afferent/efferent arterioles
- Predominantly afferent
- (2) RAAS
Myogenic Mechanism
- Vascular smooth muscles
- Contract when stretched
- eg. Afferent arterioles contract in hypertension
Regulation of GFR
Falling Arterial BP
RAAS (Renin-Angiotensin-Aldosterone System)
- Low BP / Low serum Sodium
- Angiotensinogen (Liver)
- Renin (Granular JGA)
- Ang + Renin = Ang I
- Ang I + ACE = Ang II (Lungs)
Ang II works on Adrenal Glands & Kidney
- Constrict arterioles Kidney
- Aldosterone Adrenal Glands
- ADH production Brain
Ang II on Kidney
- Vasoconstriction in arterioles
- Low Conc: Constriction of Efferent
- High Conc: Both Afferent & Efferent but Efferent more
Inc BP
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Autoregulation
Tubulo-glomerular feedback
- Macula densa of JGA sense NaCl
- (1) Regulation of afferent/efferent arterioles
- Predominantly afferent
- (2) RAAS
Rising Arterial BP
RAAS (Renin-Angiotensin-Aldosterone System)
- High BP / High serum Sodium
- Reduced Renin (Kidney)
- Reduced Ang II
Reduced uptake of Na & Vasoconstriction
- Reduced GFR as efferent relaxes more
Autoregulation
Tubulo-glomerular feedback
- Macula densa of JGA sense NaCl
- (1) Regulation of afferent/efferent arterioles
- Predominantly afferent
- (2) RAAS
Myogenic Mechanism
- Vascular smooth muscles
- Contract when stretched
- eg. Afferent arterioles contract in hypertension
Regulation
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ECF Volume
- Stretch-receptors
- Major: Na+
**Diabetic Ketoacidosis --> Decreased ECM
- Glucose excess
- Reduced reabsorption
- Pulls water out
- Vomiting
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