Forensic Medicine

Monday, August 31, 2015

Renal Physiology

·         Tf/P ratio = 1 means substance is freely filtered.
If less than 1, substance is not freely filtered.
·         In ACIDOSIS: K+ filtration: increase, Serum K+: decrease, K+excretion: increases
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·         The H+ produced is buffered mainly by the large amount of hemoglobin in the red blood cells. Bicarbonate is not an effective buffer of volatile acid.(CO2).

·         The major structural differences between epithelial cells of the proximal and distal tubules account for the fact that 65% of glomerular filtrate is reabsorbed in the proximal tubule and that the proximal tubule is more permeable to water.

The proximal tubule has an extensive brush border composed of numerous microvilli, which markedly increase the surface area for reabsorption, and the tubule also has an extensive network of intracellular channels.

The distal tubule has many more tight junctions between cells, which makes it less permeable to water. No significant difference in basement membrane thickness is observed between the proximal and distal tubules.

·         The macula densa senses the chloride concentration of the fluid flowing from the ascending limb of Henle's loop into the distal convoluted tubule.
An increase in NaCl concentration occurs when the amount of fluid flowing through the ascending limb increases because there is less time available for the reabsorption of NaCl. The resulting increase in Cl– concentration results in the release of adenosine from the macula densa.
Adenosine constricts the afferent arteriole resulting in a decrease in filtration and a return of the flow rate within the nephron toward normal. This response is referred to as tubuloglomerular feedback.


·         Persistent diarrhea will result in a metabolic acidosis, due to the loss of the bicarbonate-rich secretions from the pancreas and gallbladder. The ensuing metabolic acidosis will decrease the plasma concentration of HCO3–, decreasing the amount of bicarbonate that is filtered into the proximal tubule. At the same time, the metabolic acidosis will increase ammonia production by the proximal tubule as well as H+ secretion and production of new bicarbonate by the distal nephron. Because the metabolic acidosis is produced by the loss of bicarbonate, the anion gap will remain within normal limits.


·         The movement of K+ into cells is facilitated by the presence of insulin and epinephrine. During exercise, epinephrine hastens the movement of K+ into muscle cells, preventing the accumulation of K+ in the extracellular space around active muscle cells.

·         Free water clearance is the amount of water excreted in excess of that required to make the urine isotonic to plasma. It is calculated using the formula

 CH2O = V × [1 – (UNa + UK)/PNa]
Free water clearance is positive when the urine is dilute (more than a sufficient amount of water is excreted), and free water clearance is negative when the urine is concentrated (not enough water is excreted to make the urine isotonic to plasma).


·         Phosphate transporter is electrically neutral, requiring 2 Na+ molecules for every HPO42– molecule that it transports. The transporter is inhibited by parathyroid hormone (PTH).

·         Alkalosis dissociates protein molecules, which bind  ionised calcium. The hypocalcaemia opens Na+ - channels, and the influx increases the excitability of neuromuscular tissues, which releases tetanic cramps.

·         Primary hyperaldosteronism (Conn’s hypercorticism disease) and all types of secondary hyperaldosteronism also lead to hypernatraemia combined with hypokalaemia and enlarged blood volume. Cerebral failure and convulsions are alarming signs, but there are no specific symptoms and signs of hypernatraemia.( NO EDEMA)

·         Urinary buffers are necessary for effective excretion of acid, because the minimum pH of the urine is only 4.0 to 4.5. Phosphate is the primary urinary buffer.

·         Aldosterone secretion is increased when plasma concentrations of angiotensin II or potassium (K+) are increased.
·         Filtered Load = GFR / Px = 120 mL/min / 10 mg/mL = 12 mg/min
·         Excretion = Ux * V = 10 mg/mL * 1.5 mL/min = 15 mg/min
·         Secretion = 15 mg/min − 12 mg/min = 3 mg/min
·         The intracellular Na+ concentration of renal epithelial cells is pumped out of renal epithelial cells by Na-K pumps located on the basolateral surface of the epithelial cells. The Na/H exchanger and the Na-glucose transporter are located on the apical surface of the epithelial cells. Na+ is transported from the peritubular spaces to the capillaries by solvent drag.
·         The net glomerular capillary pressure (for Starling forces) is equal to the glomerular capillary pressure minus the sum of the plasma oncotic pressure and intrarenal pressure. Compression of the renal capsule increases the intrarenal pressure and therefore decreases the net capillary filtration pressure.
·         Net acid excretion = ([titratable acids] + [NH4+] − 2 [HCO3−]) × urine volume per day
·         When water is filtered across the glomerulus, the protein concentration (the oncotic pressure) within the capillaries increases, which in turn increases the efficiency by which water reabsorbed from the proximal tubule is returned to the circulatory system. If GFR increases, it results in a larger increase in oncotic pressure. This in turn increases the amount of water reabsorbed from the proximal tubule.
·         The distal nephron has a negative luminal potential because it is poorly permeable to negatively charged ions. Therefore, when Na+ is reabsorbed, negatively charged ions, primarily Cl−, lag behind, producing a negative intraluminal potential.
·         An increase in NaCl concentration occurs when the amount of fluid flowing through the ascending limb increases because there is less time available for the reabsorption of NaCl. The resulting increase in Cl− concentration results in the release of adenosine from the macula densa. Adenosine constricts the afferent arteriole resulting in a decrease in filtration and a return of the flow rate within the nephron toward normal. This response is referred to as tubuloglomerular feedback. If NaCl concentration decreases, for example, when circulating blood volume decreases, the decreased Cl− concentration results in the release of renin from granular cells of the juxtaglomerular apparatus.
·         Nitric oxide dilates the afferent arteriole and constricts the efferent arteriole, producing a rise in glomerular capillary pressure (and glomerular filtration) without having much of an effect on renal blood flow.
·         Prostaglandins, bradykinin, and dopamine all increase renal blood flow. Cyclooxygenase inhibitors, such as aspirin, that decrease prostaglandin synthesis may impair renal blood flow sufficiently to exacerbate the effects of renal failure.
·         Phosphate is almost completely reabsorbed in the proximal tubule, so its concentration decreases along the length of the tubule.
·         ANP increases Na+ excretion by decreasing the amount of Na+ reabsorbed from the inner medullary collecting duct by decreasing the permeability of the apical membrane of the collecting duct epithelial cells. Less Na+ is able to enter the epithelial cells and therefore, less Na is reabsorbed. ANP also increases Na+ excretion by increasing the filtered load of Na+.
·         The proximal tubule reabsorbs approximately two-thirds of the filtered water and two-thirds of the filtered Na+, Cl–, and K+. Therefore, the concentration of these substances is the same at the beginning and end of the proximal tubule. Because creatinine is not reabsorbed, its concentration increases from the proximal to distal ends of the proximal tubule. Phosphate, however, is almost completely reabsorbed in the proximal tubule, so its concentration decreases along the length of the tubule.

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