** Accordingly GFR can be estimated by using one urine sample and do creatinine testing.

Transcription

1 This sheet includes the lecture and last year s exam. When a patient goes to a clinic, we order 2 tests: 1) kidney function test: in which we measure UREA and CREATININE levels, and electrolytes (Na+, K+... etc) ** keep in mind that Creatinine is more sensitive than Urea. As Urea levels might increase in blood due to many conditions (GI bleeding, dehydration, any hypermetabolic disorders (i.e Thyrotoxicosis))... ** Accordingly GFR can be estimated by using one urine sample and do creatinine testing. egfr= (140-age)*BM / 72*PCr (mg/dl) this equation applies in males multiply by 0.85 in females. BM: Body mass which equals Height in cm 100 (approximately). ** In children we take Height in cm and multiply it by K which is a given constant. So the equation becomes egfr= Height in cm* K / serum Cr. * GFR tells you how many nephrons are active ( when it is reduced to the half, the patient would have already lost 1 million nephrons) 2) Urine analysis (Urinalysis): ROTINE and MICROSCOPY. * in routine we test for glucose- and protein- presence, specific gravity and Ph. ** in microscopy we test for WBCs in urine as well as RBCs in urine (hematuria: which could be either microscopic (seen under the microscope) or macroscopic (an evident bleeding seen with the naked eye)) - 2 to 3 RBCs in urine are considered as normal. - Hematuria is Cancer unless proven otherwise (especially painless hematuria). Now if GFR increases, the patient will start excreting important usually totally reabsorbedsubstances. (i.e glucose (glycuria) and proteins). So that glucose clearance theoretically will converge at some point with inulin clearance (the same applies for PAH even though the mechanism is due to saturation of secretion mechanism rather than reabsorbtion). PAH clearance Inuline clearance Glucose clearance

2 However, if GFR is decreased, urea and uric acid will accumulate in the blood (i.e Uremia). *previously Uremia used to stand for Chronic renal failure. GFR Control: *the dr keeps repeating previous information. Starling forces: we have four forces that govern the GFR.. the Capillary (glomerular hydrostatic pressure, the Colloid osmotic pressure, the tubular fluid s colloid osmotic pressure as well as the tubular fluid s hydrostatic pressure). **Forces that increase GFR are the capillary Hydrostatic pressure as well as the tubular colloid osmotic pressure (which equals zero here (rem: proteins are not filtered)). Here the capillary hydrostatic pressure is the highest among other capillaries in the body (usually 7 mmhg to 30 mmhg) whereas in the kidneys it is 60 mmhg. **the hydrostatic blood pressure source is the heart (the lt. Ventricle) **Forces that decrease GFR are the tubular hydrostatic pressure (18 mmhg) as well as the capillary colloid osmotic pressure (32mmHg on the average). As filtration occurs throughout the whole length of the capillaries, the filtered amount of plasma is huge enough to cause changes in proteins concentrations. Making the colloid osmotic pressure variable throughout the length of the capillaries (28 mmhg at the beginning, and 36 at the end). This doesn t occur in other capillaries in the body, as filtration is usually minimal. GFR= Driving force * permeability. Keep in mind that the driving force is the net force of starling forces ( = 10 mmhg) & that permeability has to do only with the properties of the capillaries (thickness, surface area and so on) and it is the highest in the body (in kidneys it is the highest, whereas it is very low in lungs). Permeability here = 125/10 = 12.5 ml/mmhg. ** So if I want to control GFR I need to manipulate those in the GFR law. Here we can manipulate only the capillary hydrostatic pressure. (keep in mind starling forces here are 3 not 4, as the colloid interstitial osmotic pressure (tubular, bowman s) is equal to ZERO). Capillary hydrostatic pressure is increased by vasodilating the afferent arteriole and constricting the efferent. But the constriction of the efferent shall increase it up to a certain limit, beyond that limit it decrease GFR (Because beyond that limit proteins start accumulating in the capillaries, and thus the colloid osmotic pressure increases). Blood enters the kidneys through the renal artery which is a branch of the abdominal aorta. MAP= 100 mmhg

3 Afferent = 85 mmhg at the beginning and 60 mmhg at its end. (25% of the resistance) Efferent = 59 mmhg at its begging and 18 mmhg at its end (main site of resistance, 40% of it) In the capillaries= 8 mmhg (almost 10% of the resistance) ** Administrating NSAIDs will inhibit prostaglandin synthesis (which is a vasodilator) by inhibiting the enzymes in the pathway of synthesis, leading to vasoconstriction of the afferent arteriole, decreasing the GFR, thus damaging the kidneys (do renal function test regularly). ** if GFR increases the tubular fluid flow decreases leading to cysts formation and obstruction of the tubules, which already have a narrow lumen. ** GFR remains constant due to Uncoupling of the systemic blood pressure and the renal (afferent arteriole) hydrostatic blood pressure, within certain limitations (70 mmhg 150 mmhg) GFR Here the dr gives an example of uncoupling, excitation contraction uncoupling. Usually contraction follows excitation. However, if we remove the T-tubules effect by an osmotic shock, there will be excitation with No contraction. And that is the concept of uncoupling. ** Uncoupling of the earlier mentioned hydrostatic pressures is called renal auto-regulation. **Macula densa: the cells of the distal tubules are like a scissor, intervening between the afferent and efferent arterioles, so that when they touch each other, cells will become darker. And these cells are sensors for electrolytes concentrations. **So when GFR decreases (like in bleeding or hypotension) the amount of electrolytes reaching the distal tubule is less, so macula densa are activated, sending two impulses: The first one is to the afferent arteriole causing vasodilatation, thus increasing GFR. The second one is to a group of special muscle cells that are located in the walls of afferent arterioles, which respond by secreting renin (proteolytic enzyme) cutting out 4 amino acids of a fourteen amino acid molecule (angiotensenogen, which is produce by the liver), producing ang I which goes to lungs and is converted by ACE to Ang II ( by cutting out 2 AAs). Ang II: 1) systemic vasoconstrictor, thus increasing blood pressure.

4 2) Goes to the Zona Glomerulosa of the adrenal glands, stimulating Aldosterone secretion, which in turn goes to the distal tubule and collecting duct and stimulates the reabsorbtion of Na+ and H2O. But increasing K+ excretion. 3) There are receptors for Ang II on the efferent arteriole, leading to its vasoconstriction and increasing the GFR. Whereas no Ang II receptors are found on the afferent arteriole. 4) Goes to the proximal tubule and directly stimulates Na+ reabsorbtion. A patient comes to the clinic, presentation: either Acute (days weeks) or chronic (months years) renal failure. **Acute renal failure will cause oliguria (less than 300 ml urine/ M^2 body surface area/ day OR 450 ml/day OR 20 ml/min). There are three related conditions: 1) Pre-renal causes: Post MI, dehydration, bleeding, diarrhea, hypotension...etc... In that case we reduced blood amounts reaching the kidneys, might not cause ischemia and hypoxia for the cells (as 20% of the 1250 ml of blood reaching the kidneys are enough to keep the cells intact) but in this case they won t perform their function and won t form urine properly. 2) Intra-renal is either glomerulonephritis (from the bloodstream) or tubulonephritis (urinary tract). Or that it might be caused by toxins from blood (like heavy metals). If I want to differentiate between the mentioned two types, a patient will present with oliguria, or might even with isoosmotic polyuria. Either ways the differentiation is based on the Urea:Creatinine ratio (NORMAL 10:1) in the pre-renal it becomes elevated (i.e 20:1) but in the intra-renal it remains normal. And the mentioned two cases account for 90% of all acute renal failure. 3) 10% of the cases are post-renal. Those are due to OBSTRUCTION. If the obstruction affects one kidney (i.e from the ureter and above) it is usually milder. However, if it was below that level the effect will be on the two kidneys (major pathological condition that needs urgent intervention like obstruction of prostatic urethra). Haemodialysis: A mechanism that is used to clear the body from waste products, by using Semi-permeable membrane that allows solutes to move down their Gradient (from blood compartment to the applied fluid compartment. Nevertheless, this mechanism can never control the {Hb}, as it washes out Erythropioten out from the blood (one of last year s exam questions) Hypoosmotic fluid with low pressure Blood comes in, allowing substance exchange, then goes back

5 Last year s Exam: 1) Regarding ECF which is not true: o {cations} = {anions} true due to electro-neutrality. o Osmolarity predicted by {Na+} true {Na+}*2.1 o Sodium is the major ECF cation o Proteins are the major EC buffers. FALSE (INTRACELLULAR) o Both ICF and ECF have the same osmolarity 2) All of the following regarding clearance is correct EXCEPT: (a) It can rise, fall or stay the same if the relative solute concentration increases. (b) Glucose clearance is normally zero. (c) Inuline clearance is always constant regardless of plasma concentration. (d) If greater than GFR, always indicative of secretion. (e) If less than GFR always indicative of reabsorption. might indicate NO or REDUCED FILTRATION When you increase the plasma concentration of PAH, which of the following will increase: (a) Clearance (b) Excretion rate (c) Filtration fraction (d) Production Rate (e) Reabsorption Rate Where does renal vascular resistance reside the most: (a) Afferent arterioles (b) Efferent arterioles (c) Glomerular capillaries (d) Peritubular capillaries (e) Renal vein Under normal physiological conditions and no exercise, compared to plasma, urine has: (a) Lower ph, lower osmolarity, higher K+ (b) Higher ph, lower osmolarity, higher K+ (c) Higher ph, higher osmolarity, higher K+ (d) Lower ph, higher osmolarity and higher K+ plasma {K+} is low. (e) Equal ph, higher osmolarity, equal K+ Which of the following regarding acid-base balance is FALSE: (a) During respiratory acidosis, CO2 increases and ph decreases. (b) During compensation of respiratory alkalosis, CO2 increases, HCO3 increases and ph is increased. (c) Metabolic acidosis can be due to vomiting. (d) Chronic renal failure is associated with metabolic acidosis. (e) During metabolic acidosis, HCO3 decreases as a compensatory mechanism. (as it is the cause of the case not compensation) Under very high levels of ADH, where is water most absorbed? (a) Proximal Tubules always two thirds are reabrorbed from here

6 (b) Late distal tubules (c) Early distal tubules (d) Collecting ducts (e) Collecting tubules All of the following can be changed by hemodialysis EXCEPT: (a) Hemoglobin concentration (b) Plasma K+ (c) Urea (d) Plasma acid-base balance (e) Blood Volume