April 12 Lectures

Danielson I

Clearance of creatine = GFR   
amount of creatinine excreted is constant (depending on body size, muscularity) - this means that U x [Cr]u is constant.   The amount of creatinine leaving plasma is V x [Cr]p.
The amount leaving plasma is always equal to the amount in urine, so V x [Cr]p = U x [Cr]u.  For creatinine, V = GFR because there is only filtration, no secretion or reabsorption.

Using normal values; GFR x [Cr]p = U x [Cr]u or 125 ml/min x 1 mg/dL = 1 ml/min x 125 mg/dL

Renal failure = decreased GFR.  this means that plasma creatinine will be increased until new steady state is reached and urinary excretion is stable.

examples          GFR x [Cr]p = U x [Cr]u     62.5ml/min  x 2 mg/dL = 1 ml/min x 125 mg/dL
                                                                       41.2ml/min  x 3 mg/dL =  1 ml/min x 125 mg/dL
                                                                       50 ml/min x 5 mg/dL =  1 ml/min x 125 mg/dL

Danielson II

Proximal tubule

• early and late - filtered HCO3 is reabsorbed (Carbonic anhydrase essential for this)
• early - tight junctions - water not permeable; lots of cotransport of solutes
• late - organic acids sereted (antiporter with chloride); water reabsorbed via osmosis into blood  (volume expansion dilutes oncotic pressure in peritubular caps causing decreased water reabsorption - volume contraction (dehydration) leads to higher oncotic pressure and more water reabsorption. volume contraction can cause an alkalosis due to the stimulation of higher Angiotensin II (AT2)levels.  Increased AT2 stimulates Na-H antiporter leading to higher HCO3 levels in blood.

Contraction Alkalosis - also occurs passively with volume changes; e.g., due to diuretics.
http://fitsweb.uchc.edu/student/selectives/TimurGraham/Contraction_Alkalosis.html


Loop of Henle

• descending - permeable to water, salt, and urea
• thin ascending - salt reabsorption, no water
• thick ascending - not permeable to water - active transport of NaCl, K out of lumen into blood, dilutes lumen to hypotonic

distal tubule sourrounded by afferent and efferent arterioles; JGA fine tunes final salt excretion - aldosterone, ADH

• early - macula densa respond to JGA signals; reabsorption of NaCl, hypotonic fluid in DT
• late - principal cells and intercalated cells; NaCl, K reabsorption; water reabsorption (via aquaporin channels - regulated by ADH)
• collecting duct - aldosterone, ADH

Renin secretion regulated by blood pressure (also potassium, sympathetic NS)

Aldosterone receptor is transcription regulator.  upregulates pumps and transporters of principal cells. 

Practice question:  Conn's syndrome is a disease of the adrenal glands involving excess production of aldosterone (primary hyperaldosteronism).  Predict the effect of this condition of urine and plasma Na, K, HCO3, and pH.

Other practice questions


Barry

kidneys 0.5% body weight receive 25% of cardiac output = 1700 L per day = blood flow through kidneys       -  out of this the kidneys produce about 1 L of urine.

many diseases of glomerulus are immune mediated.  specific cause usually not known.
damage from in situ antigens (e.g., on podocytes) or by circulating antigen-antibody complexes (e.g., Lupus)

nephrotic syndrome - immune but not-inflammatory.  >3.5 g protein/day; hypoalbuminemia; hyperlipidemia (increased production by liver).  Enhanced hepatic synthesis of lipoprotein lipids may be stimulated by a decreased plasma albumin concentration or oncotic pressure (N Engl J Med 1985; 312:1544–8.)

urine - oval fat bodies.  Edema due to decreased osmotic pressure PLUS salt and water retention.

Minimal Change Disease  - damaged podocytes not seen with light microscopy - no immune deposits by immunoflorescence but immune dysfunction that damages podocytes