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Glomerular Filtration (Glomerular Filtration Rate Is Regulated By Systemic…

- - - - Renin hormone is produced by afferent arteriole mesangial cell ( specialized juxtaglomerular cells ).
        
        Renin release is stimulated by ↓ renal perfusion pressure ( systemic hypotension).
        
        Renin convert angiotensin (from liver) to angiotensin I.
        
        Angiotensin Converting Enzyme (ACE) convert angiotensin I to angiotensin II.
        
        Angiotensin II is a vasoconstrictor, ↑ systemic blood pressure and renal perfusion pressure.
        
        Angiotensin II also stimulates adrenal gland to release aldosterone , pituitary to release vasopressin → activates Na uptake in proximal convoluted tubule(PCT) and collecting duct (CD).
        
        Enhance salt and water retention, intracellular volume ↑, vascular resistance ↑ ==→ ↑ systemic blood pressure and renal perfusion pressure.
        
        Renin release is suppressed by ;- (1) high renal perfusion. (2) high plasma angiotensin II → -ve feedback mechanism for the system.
        
        Angiotensin II release PGE2 and Prostacyclin , without this, vasoconstriction ↓ renal blood flow and GFR.
  - - - Glomerular arteriole respond to changes in arteriolar wall tension.
        
        Arteriolar wall tension ↑, afferent arteriole constrict, ↑ blood flow resistant,↑ blood pressure.
        
        Arteriolar wall tension ↓, afferent arteriole dilate, ↓blood flow resistant,↓ blood pressure.
    - - Macula densa at DCT, located between afferent and efferent glomerular arteriole.
        
        Juxtaglomerular apparatus;- (1) macula densa, (2) extraglomerular mesangial cell,(3) afferent arteriole, (4) efferent arteriole.
        
        ↑[NaCl] in tubule fluid, activate macula densa signaling cascade.
        
        Signaling paracrine factors ;- NO, adenosine, ATP- suppress renin release, ↑ resistance,↓ renal perfusion pressure, mesangial cell contract,↓ Kf.
        
        This tubuloglomerular feedback only respond to single nephron GFR, prevent tubule fluid flow rates > transport capacity, prevent excessive fluid and solute loss.
        
        Glomerular endothelium produce endothelin thromboxane A2 ( metabolic arachidonic acid ) and angiotensin II as vasoconstrictor.
        
        And produce vasoldilator/ relaxing factor = NO, prostacyclin, PGE2
        
        NO produced by oxidation of L-arginine by NO synthase isoform.
        
        NO quench reactive O2 species, inhibit intrarenal vasoconstriction, glomerular hypertension, mesangial cell proliferation, and mesangial matrix production.
        
        Angiotensin II, aldosterone, vasopressin ( antidiuretic hormone) - enhance water and solute reabsorption ,↑ blood volume.
        
        Atrial Natriuretic peptides (ANP) cause natriuresis( Na wasting) and diuresis (water wasting) and ↓ blood volume.
    - - Vessel tone systemic factor ;- systemic blood pressure, renal perfusion, ultrafiltration.
      - Vasopressin and catecholamines → systemic vasocontriction → ↑BP.
      - β- adrenergic stimulation activate renin- angiotensin - aldosterone system.
      - α- adrenergic stimulation cause renal vasoconstriction → ↓renal blood flow.
      - vasoconstrictors → mesangial cell contract → ↓ area available for filtration.↓Kf.
      - Kf = area available for filtration x hydraulic permeability.
      - mesangial cell contract, ↓ area availablle for filtration,↓ Kf, ↓ GFR.
      - Insulin-like growth factor & high dietary protein→ enhance GFR.
      - Insulin-like growth factor ↑ GFR.
      - High dietary protein ↑ renal blood flow,↑GFR.- rapid progression of glomerular injury→ renal failure.
      - In Birds, GFR more variable, exhibit intermittent filtration in reptilian type glomeruli←dehydration and ↓GFR,← release or arginine vasotocin.
      - Arginine vasotocin cause constriction in reptilian nephron.
      - Macula densa is absent/ rudimentary and no tubuloglomerular feedback in birds.
- - - - A 15 years old cat, listless, inappetent, thin, drinking more water, urinate large volume, vomiting frequently. The cat is moderately dehydrated, mucous membrane pale, kidney small and slightly irregular, hematocrit 22%( normal, 30-42%), serum creatine level is 8.7mg/dL ( normal, 0.5-1.2 mg/dL). The cat has chronic renal failure and common in old cat,serum creatinine level high as the glomerular loss function and reduced GFR. The urine is not cconcetrated in response to dehydration because tubular function compromised. The small kidney is due to gradual nephron loss. Anemia is common due to decreased erythropoietin production by the kidney.
    - - Rehydration by intravenous fluids and correction of electrolyte and acid base disturbances.Diet with low total protein, low sodium, low phosphorus. Supplementing with water-soluble vitamin could help. Anabolic steroid help improve anemia with exogenous erythropoietin.
  - - - A 3 year old spayed dog not eating well, and tire easily for several days. The dog seems bright , alert, and in good flesh. The dog has slight pitting edema in distal extremities.Left kidney is palpable and feels smooth with normal size. Urinalysis shows 3+ proteins ( normal, -ve to trace amount), presence of few RBC, complete blood cell count is normal. Serum albumin level of 1.5g/dL (normal. 2.3 -4.3 g/dL). The dog has acute glomerulonephritis because the filtration barrier for protein is damaged and become leaky, thus protein appear in urine. Loss of albumin cause the serum albumin level drops.The peripheral edema is caused by hypoalbuminemia, which lower the intracapillary oncotic pressure and leakage of fluid into extravascular space.Renal biopsy is necessary to verify the type and severity of glomerular injury. Potential cause of glomerulonephritis is concurrent bacterial or viral infections or autoimmune diseases.
    - - Immunosuppressive and anti-inflammatory agents are used to combat ongoing damage from glomerular inflammation. Hypoalbuminemia must be treated with plasma/ other colloids . Frequent assessment of urine protein/ creatinine ratios and serum creatinine is warranted to monitor disease progression.