Term
| Body Fluid Compartments and volumes |
|
Definition
| We are all about 60% water. 2/3 of this water is in cells (intracellular fluid, ICF) and 1/3 is outside cells (extracellular fluid, ECF). Of the ECF, 1/4 is in the blood plasma and the other 3/4 is outside blood vessels and between cells – the interstitial fluid. |
|
|
Term
| What controls concentration and volume of the ECF respectively. |
|
Definition
Concentration: Thirst and ADH.
Volume: Sodium excretion |
|
|
Term
| symptoms of glomerular vs tubular disease |
|
Definition
| Diseases of the glomeruli typically cause fluid retention with edema or hypertension. Glomerular diseases also often cause protein and/or red cells to appear in the urine. Diseases of the tubules and interstitium tend to cause high urine volume (polyuria) and nocturia, and a tendency to volume depletion with normal or low blood pressure. |
|
|
Term
|
Definition
| Glomerular disease. Losing more than 3.5 g of protein each day. the heavy protein loss causes hypoalbuminemia: edema and hypercholesterolemia are usual accompaniments. |
|
|
Term
|
Definition
| Glomerular disease. hypertension is common; in acute cases there may be oliguria (reduced urine volume), hyperkalemia, and acute renal failure. Pores are large enough to allow RBCs to pass through. |
|
|
Term
| three requirements for excretion of adequate amounts of dilute urine |
|
Definition
1) There must be adequate fluid delivery to the diluting segment (thick ascending limb of Henle). If fluid delivery out of the proximal tubule should be greatly reduced (perhaps by a fall in ECF volume), then less fluid will be available for the formation of dilute urine.
2) The thick ascending limb must reabsorb sodium normally.
3) The collecting duct must remain impermeable to water |
|
|
Term
| are two classes of stimuli that cause ADH release |
|
Definition
| : osmotic and pressure stimuli. An increase in osmolality activates osmoreceptors that increase ADH release, while a decrease in pressure in the arterial or venous side of the circulation activates baroreceptors, which stimulate ADH release |
|
|
Term
| Osmolality, Pressure and ADH release. |
|
Definition
| small increases in osmolality stimulate, while larger percent changes in pressure are required to alter ADH secretion. In contrast, the greatest ADH release occurs in response to large decreases in pressure. Finally, if pressure decreases substantially, even if plasma osmolality falls, ADH release will be stimulated - the body preserves pressure before all else. |
|
|
Term
| Syndrome of inappropriate ADH secretion (SIADH) causes. |
|
Definition
a. Pulmonary disease - certain pulmonary cells (source not entirely clear) can be induced to secrete ADH in the setting of inflammation or infection.
b. Carcinomas - tumors originating in many sites can release ADH, particularly small cell lung carcinomas.
c. CNS disease - a large variety of CNS disorders, including infection, tumors, and strokes, can cause enhanced ADH release by the hypothalamus.
d. Drugs - Several drugs have been implicated (a complete listing is not indicated). Note that any patient with suspected SIADH should have their medications carefully examined. Of note, oxytocin has ADH properties and can cause hyponatremia. |
|
|
Term
| The criteria for diagnosis of SIADH |
|
Definition
a. Low serum osmolality and hyponatremia
b. Urine which is less than maximally dilute
c. Urine sodium matches intake
d. Absence of other disorders impairing urine dilution
e. Improvement in hyponatremia after water restriction |
|
|
Term
|
Definition
| Increases Na reabsorption. K+ sparing dieuretics block the aldosterone receptor |
|
|
Term
| SIGNS AND SYMPTOMS OF HYPONATREMIA |
|
Definition
| Rapidity of correction of hyponatremia should be proportional to the rate of onset on hyponatremia. Due to ECF hypotonicity, water moving into cells and cell swelling. The brain has little room to expand in the skull - most symptoms of hyponatremia are due to brain edema. severity and the time course of development of hyponatremia are important determinants of the signs and symptoms that evolve. |
|
|
Term
| Primary renal water loss (without sodium loss) |
|
Definition
| occurs in central (failure to secrete adequate amounts of ADH) or nephrogenic (failure to respond to ADH) diabetes insipidus. |
|
|
Term
|
Definition
| The hypertonicity of the ECF draws water out of brain cells, leading to shearing of the vessels of the brain. The duration of hypernatremia also dictates the rate of correction. Symptomatic patients need to be rapidly treated, however patients with long-standing hypernatremia should be gradually corrected - if the correction is too rapid, idiogenic osmoles in brain cells will not have time to disappear and will pull excess water into the brain cells, causing cerebral edema. |
|
|
Term
| DIFFERENTIAL DIAGNOSIS OF POLYURIA |
|
Definition
| osmotic diuresis, diabetes insipidus or primary polydipsia. |
|
|
Term
| water deprivation test to distinguish central, nephrogenic DI and pschogenic polydipsia |
|
Definition
| complete central DI, urine osmolality does not change with water deprivation despite increased plasma osmolality. If ADH is given, urine osmolality rises, but not maximally because of chronic decreases in aquaporin-2 – this takes several days to normalize. In patients with severe nephrogenic DI, urine osmolality does not rise with water deprivation and ADH has no effect. In patients with psychogenic polydipsia, urine osmolality rises with water deprivation but not maximally. ADH has no effect at this point. This failure to maximally concentrate is partially due to washout of the medullary hypertonicity – this takes several days to restore to normal. |
|
|
Term
| G protein linked second messengers, receptor, class and actions |
|
Definition
Qiss (kiss) and qiq (kick) till you’re siq (sick) of sqs (sex). a1, a2, b1, b2, M1, M2, M3, D1, D2, H1, H2, V1, V2.
Gq = Increase in Phospholipase C = Increase in IP3, Ca2+, DAG, and Protein Kinase C.
Gs (stimulatory) = Increase in Adenyly cyclase = Increase in cAMP and Protein Kinase A.
Gi (inhib) = Blocks Adenylyl Cyclase = decrease in cAMP and Protein Kinase A |
|
|
Term
| most important causative factor for renal sodium retention in cirrhosis. |
|
Definition
| Decreased total peripheral resistance due to the liver failing to degrade or overproducing vasodilating factors. These factors lead primarily to a marked fall in mesenteric (splanchnic) vascular resistance and blood pooling. |
|
|
Term
| Treatment of hyperkalemia due to metabolic acidosis |
|
Definition
| Loop Diuretic eg. furosemide |
|
|
Term
| net ultrafiltration pressure |
|
Definition
|
|
Term
| glomerular filtration rate |
|
Definition
GFR = Kf*PUF
GFR = (Ucreatinine x V)/Pcreatinine |
|
|
Term
|
Definition
Cx = (Ux x V)/Px
Cx is the clearance of substance x from the plasma,
Ux equals the concentration of substance x in the urine,
V equals the flow rate of the urine,
Px equals the concentration of substance x in the plasma. |
|
|
Term
|
Definition
RPF = (UPAH x V)/P^aPAH
UPAH= urine concentration of PAH
V = urine flow rate
PPAH = plasma concentration of PAH |
|
|
Term
|
Definition
| RBF = (ERPF)/(1.0 – Hematocrit) |
|
|
Term
|
Definition
Filtration Fraction = GFR/RPF
GFR: Glomerular filtration rate
RPF: Renal plasma flow |
|
|
Term
|
Definition
| Filtered Load = GFR x plasma concentration |
|
|
Term
|
Definition
total body water = 60% of weight = 0.60*(body weight)
intracellular fluid = 40% of weight = 0.40*(body weight)
extracellular fluid =20% of weight = 0.20*(body weight)
interstitial fluid = 15% of weight = 0.15*(body weight)
plasma = 5% of weight = 0.05*(body weight) |
|
|
Term
| Renal Blood Supply and Vasculature |
|
Definition
| renal artery branches off the abdominal aorta. A single renal artery enters the kidney and divides into segmental arteries. It divides to form the interlobar arteries, which pass between the renal pyramids and then further divide to form arcuate arteries which parallel the cortico-medullary junction. The arcuate arteries branch into interlobular arteries which then divide into numerous afferent arterioles, then glomerulus then efferent arterioles, then peritubular capillaries. |
|
|
Term
|
Definition
represent about 85% of the
total nephron population and are characterized by superficial
glomeruli and short loops of Henle which are restricted to the
outer medulla. bulk reabsorption
and secretion. Glomeruli of cortical nephrons arise from afferent arterioles which branch off interlobular arteries. The efferent arterioles of these nephrons then perfuse
peritubular capillaries. involved in general reabsorption of solutes and water and interact with a peritubular capillary bed |
|
|
Term
|
Definition
represent about 15% of the total nephron population and are characterized by deeper glomeruli and long loops of Henle which are located in the inner medulla. With their long loops of Henle the juxtamedullary nephrons play an important role in concentrating urine. afferent arterioles of juxtamedullary nephrons arise from arcuate arteries (or the very proximal portion of interlobular arteries) and the efferent
arterioles perfuse the vasa recta. |
|
|
Term
| The Juxtaglomerular Apparatus |
|
Definition
| involved in the autoregulation of renal blood flow and glomerular filtration rate. It is composed of the following: 1) the macula densa (MD) a set the thick ascending limb cells found between the afferent and efferent arterioles, 2) extraglomerular mesangial (EM) cells (Lacis cells), and 3) the reninproducing granular cells of the afferent and efferent arterioles. The thick ascending limb of the loop of Henle projects to the glomerulus of its own nephron and passes close to its afferent and efferent arterioles. |
|
|
Term
| Side effects of Hydrochlorothiazide |
|
Definition
| Hyper GLUC (Glycemia, Lipidemia, uricemia, and calcemia) also sulfa allergy and hypokalemia metabolic acidosis and hyponatremia |
|
|
Term
| glomerular basement membrane (GBM) |
|
Definition
composed of three layers: the lamina rara interna, lamina densa, and lamina rara externa. These layers are generated by the podocytes and capillary endothelium. The GBM functions
to restrict the passage of intermediate to large-sized solutes (> 1 KDa). |
|
|
Term
|
Definition
| forms fenestrations (pores) between the cells which are about 700Å in size and freely permeable to water, small solutes, and small proteins. The capillary endothelium forms a barrier to cells and large circulating proteins |
|
|
Term
|
Definition
interdigitate to form filtration slits of about 40Å - 140Å. The slits prevent the passage of proteins and
macromolecules. Like mesangial cells,
contraction and relaxation of podocyte foot processes can influence glomerular filtration. Like GBM also has a negative charge. |
|
|
Term
|
Definition
| The S1 is highly convoluted; the S2 segment is somewhat convoluted. Segment S3 is straight. All three are located in the cortex but S3 projects into outer medulla. specialized for bulk transport of ions, solutes and water with extensive apical (tubule) and basolateral (blood) membranes characterized by a well developed apical brush border, numerous mitochondria. Cell complexity progressively declines along the length of the proximal tubule. |
|
|
Term
| descending thin limb (DTL) |
|
Definition
| permeable to water and urea, can be distinguished from the other thin portion of the nephron, the ATL, by its expression of aquaporin 1 (AQP1) and the urea transporter type-A (UTA). |
|
|
Term
| ascending thin limb (ATL) |
|
Definition
| permeable to sodium, chloride and urea,The ATL can be functionally distinguished from the DTL by the expression of the Na+/K+/2Cl- (furosemidesensitive) cotransporter. |
|
|
Term
| thick ascending limb (TAL) |
|
Definition
located in the outer medulla and cortex where it transitions into the distal convoluted tubule (DCT). The macula densa, an important part of the juxtaglomerular apparatus, is located at this transition. The TAL can be distinguished from the DTL and
ATL by its larger appearance (i.e. larger tubular external diameter). Like the ATL, the TAL expresses the Na+/K+/2Cl- (furosemide-sensitive) cotransporter. |
|
|
Term
| distal convoluted tubule (DCT) |
|
Definition
| The DCT can be further distinguished from other segments by the expression of the Na+/Cl- (thiazidesensitive) cotransporter. |
|
|
Term
connecting segment (CNT; a.k.a.
connecting tubule) |
|
Definition
| Shortest nephron segment, located entirely in cortex. plays an important role in sodium and calcium reabsorption. It can be distinguished from other segments by specific expression of kallikrein (a proteolytic enzyme which regulates capillary permeability and smooth muscle tone via kinins) and calbindin-D-28K (a calcium binding protein). |
|
|
Term
|
Definition
| only nephron segment that is found in the cortex, outer medulla and inner medulla. only nephron segment that is made up of two different epithelial cell types; principal cells and intercalated cells. |
|
|
Term
|
Definition
make up approximately 30% of the collecting duct and play an
important role in acid and base balance. Intercalated cells can be further divided into type- A (, which secrete acid), type-B (, which secrete HCO3 -) and type-non-A/B. Type-A intercalated cells express the H+-ATPase on the apical membrane, while type-B Intercalated cells express the H+-ATPase on the basolateral membrane. Intercalatedcells play a role in K+ absorption and, reflective of their high rates of ATP-driven transport,contain numerous mitochondria. |
|
|
Term
|
Definition
make up ~70% of the cells in the collecting duct and play an important role in water and salt regulation. Morphologically, they can be distinguished from intercalated
cells by the presence of a single cilium in the apical membrane. Furthermore, the apical membrane of intercalated cells bulges into the nephron lumen whereas the apical membrane of principal cells does not. Compared to intercalated cells, principal cells have a less extensive basolateral membrane network and fewer mitochondria. They function to reabsorb Na+ and Cl- and secrete K+. |
|
|
Term
|
Definition
| tightness of the junctional complexes increases from proximal tubule to collecting duct (i.e., solute/ion movement becomes progressively more restricted). |
|
|
Term
|
Definition
| urogenital system is derived from intermediate mesoderm. The production of urine begins in the mesonephros during the sixth week. After the tenth week these nephrons become inactive and atrophy. The final step is the development of the definitive kidneys, the metanephros. |
|
|
Term
|
Definition
polyfructose molecule that can be used to measure glomerular filtration rate
(GFR). It exhibits a linear relationship between plasma concentration and urinary excretion and inulin clearance is not dependent on plasma inulin concentration or on urinary flow rate. Since it is not produced by the body, it has to be injected intravenously and is more complicated than creatinine to use for assessing GFR. |
|
|
Term
Two mechanisms are responsible for the regulation of RBF and GFR, which are
pressure-dependent and flow-dependent. |
|
Definition
Myogenic mechanism is the pressuredependent component.
Tubuloglomerular feedback is the flowdependent mechanism |
|
|
Term
| Tubuloglomerular feedback |
|
Definition
is the flowdependent mechanism. The macula densa cells of the juxtaglomerular apparatus senses the tubular flow rate as well as solute
composition, which signal the afferent arteriole to adjust resistance to maintain GFR. This signal is transduced by the macula densa via adenosine. |
|
|
Term
| Regulation of Renal Blood Flow |
|
Definition
Sympathetic vasoconstrictor fibers
innervate the afferent arteriole and
induce vasoconstriction. Circulating epinephrine, or norepinephrine, induces afferent and efferent arteriolar vasoconstriction. Angiotensin II is a potent renal vasoconstrictor, Kallikrein is formed and stored in the renal cortex. This enzyme splits the potent vasodilator bradykinin from plasma globulins. In renal tissues it also synthesizes another vasodilator peptide known as kallidin. Prostaglandin E2 is a renal vasodilator produced mostly in the medullary areas of the kidney. Dopamine is found in high concentrations in the renal cortex and is a potent vasodilator. |
|
|
Term
|
Definition
| the movement of solutes and/or ions between cells. However, in the kidney, this process plays a very minor role because the space between the epithelial cells has a very high resistance to solute flow. |
|
|
Term
|
Definition
| the movement of solutes and/or ions across the cell (i.e., across the cell membranes) and represents the major transport process within the kidney. |
|
|
Term
|
Definition
| Na+-K+- 2Cl- cotransporter found in the ATL and the TAL. Furosemide blocks this pump. rate limiting step for activity of NKCC2 is the availability of luminal K+. |
|
|
Term
|
Definition
| Found in the DCT, Thiazide sensitive |
|
|
Term
|
Definition
| transport functions to regulate acid-base balance, reabsorb Na+ and H2O, secrete K+, and recycle urea |
|
|
Term
|
Definition
| Proximal tubule. Bicarbonate combines w H+ to form CO2 and H2O which is then reabsorbed and changed back into bicarbonate and H+. H+ is pumped back into the lumen via Na/H+ exchanger, and bicarbonate is transported out the basolateral surface of the cell via Na+HCO3 cotransporter. Carbonic Anhydrase catalyzes both steps inside and out of Bicarbonate to H2O and CO2 and vice versa |
|
|
Term
|
Definition
Two types of Na+Glucose cotransporters located in the proximal tubule. The
proximal portion contains a high capacity/low affinity transporter and the distal portion (where the glucose concentrations of the tubular fluid are far less) expresses a high affinity/low capacity transporter. Once inside the cell glucose is exported across the basolateral membrane via GLUT transporter that uses facilitated diffussion. |
|
|
Term
|
Definition
| Primary mechanism is a Na+ cotransporter, secondary is facilitated diffusion. Once inside the cell most use facilitated diffusion to cross the basolateral surface. Some exceptions. |
|
|
Term
|
Definition
| Same mechanism as AA except either broken down by brush border enzymes of transported in via a H+oligopeptide cotransporter and then broken down. |
|
|
Term
| Protein Handling in the kidney |
|
Definition
Proteins and polypeptides are
reabsorbed by a process of receptormediated endocytosis. The protein binds to a clathrin- coated pit at the apical membrane and is internalized as a coated vesicle. The vesicles then fuse with endosomes and the proteins are digested into free amino acids in lysosomes. |
|
|
Term
|
Definition
Some excretion of phosphate
occurs at normal plasma phosphate
concentrations. The majority of
phosphate reabsorption occurs in the
proximal tubule via a Na+Phosphate cotransporter. The kidney plays an important role in the regulation of phosphate levels. |
|
|
Term
| Counter-Current Multiplier |
|
Definition
The loop of Henle and collecting duct act as the countercurrent multipliers and are composed of the following components: 1) the descending thin limb (DTL) is permeable to water only, 2) the ascending limb is
permeable to NaCl only and 3) urea
transporters located in the collecting duct and ascending limb are involved in recycling urea from the collecting duct back to the loop of Henle; this is known as urea trapping. |
|
|
Term
| The Countercurrent Exchanger |
|
Definition
| Involves descending and ascending vasa recta. This system allows solutes to recirculate in the medulla and water, in effect, to bypass it. |
|
|
Term
| What are the major anions in the ECF and ICF respectively |
|
Definition
| chloride and bicarbonate in ECF, Phosphate in the ICF |
|
|
Term
| isotonic volume expansion, What changes |
|
Definition
|
|
Term
| hyperosmotic volume contraction, lost in desert: Sweating. What changes |
|
Definition
ECF volume: decrease.
ECF osmolarity: increase.
ICF volume: decrease.
ICF osmolarity: increase |
|
|
Term
| hyperosmotic volume expansion, excessive NaCl intake |
|
Definition
ECF volume: Increase
ECF osmolarity: increase.
ICF volume: decrease.
ICF osmolarity: increase |
|
|
Term
| hypo-osmotic volume contraction, Adrenal insufficiency |
|
Definition
ECF volume: decrease
ECF osmolarity: decrease.
ICF volume: increase
ICF osmolarity: decrease |
|
|
Term
| iso-osmotic volume contraction, Diarrhea |
|
Definition
|
|
Term
| hypo-osmotic volume expansion, SIADH |
|
Definition
ECF volume: increase
ECF osmolarity: decrease.
ICF volume: increase
ICF osmolarity: decrease |
|
|
Term
| The nephron is permeable to water in three places |
|
Definition
| 1) the PCT, 2) DTL, and 3) CD. Water moves from the tubular fluid of the PCT and DTL into the renal interstitium via the ADHinsensitive water channel aquaporin 1 (AQ1). Water moves from the tubular fluid of the CD into the renal interstitium via the ADH-sensitive water channel aquaporin 2 (AQ2). |
|
|
Term
| Sensing Changes in Osmolality |
|
Definition
Changes in osmolality are sensed by
osmoreceptors in the supraoptic and
paraventricular nuclei of the hypothalamus. Increases in plasma osmolality stimulate secretion of the anti-diuretic hormone (ADH) otherwise known as arginine vasopressin
(AVP). Osmolality is a more sensitive
stimulus of ADH secretion than
volume/pressure. |
|
|
Term
| Changes in volume/pressure are sensed by |
|
Definition
baroreceptors located in the atrium, pulmonary vessels, aortic arch and carotid sinus. There are two types of
baroreceptors: low pressure (atrium and
pulmonary vessels) and high pressure (aortic arch and carotid sinus). Decreases in plasma volume/pressure stimulate secretion of ADH. |
|
|
Term
| MEchanism of ADH leading to H2O reabsorption |
|
Definition
1) ADH binds to the vasopressin type-2 receptor (V2R) located on the basolateral membrane.
2) The ADH/V2R complex activates adenylate cyclase (AC) via the Gscoupled protein.
3) Activation of AC catalyzes the formation of cyclic AMP (cAMP) from ATP.
4) cAMP immediately activates protein kinase A (PKA) which is hypothesized to
phosphorylate membrane vesicles containing AQ2, which then insert into the apical membrane. This leads to an increase in CD water permeability.
5) cAMP also stimulates an increase in the transcription of AQ2, which leads to an increase in AQ2 abundance.
6) Water levels on the basolateral side of principal cells are regulated via two water channels, AQ3 and AQ4. |
|
|
Term
|
Definition
Mutations in NKCC2, ClCKb or ROMK result in hypokalemia, increased urinary
excretion of potassium and
prostaglandins, normal blood pressure despite elevated plasma renin and aldosterone, hypochloremia, and metabolic alkalosis. |
|
|
Term
|
Definition
Mutations in the thiazidesensitive
NaCl cotransporter result in hypokalemia, renal potassium
wasting, increased serum renin
and aldosterone with normal blood pressure, hypomagnesemia, increased urinary magnesium, and decreased urinary calcium excretion. |
|
|
Term
| The collecting duct (CD) reabsorbs 2-5% of the filtered sodium via the... |
|
Definition
epithelial sodium channel (ENaC), which is regulated by aldosterone. Activity of the basolateral Na+/K+-ATPase results
in an electrochemical gradient
favoring sodium entry across the
apical membrane. When ENaC channels open, sodium moves down its concentration gradient into the cell. Potassium brought into the cell by the Na+/K+-ATPase can be secreted across the apical membrane (into the tubular fluid) by a KCl cotransporter or through a K+ channel. |
|
|
Term
collecting duct reabsorbs Cl- by two
mechanism. |
|
Definition
the lumen negative transepithelial potential generated by principal cells favors the paracellular absorption of Cl-. In addition, -intercalated cells
absorb Cl- via a transcellular
process. Cl- enters across the apical membrane in exchange for intracellularly generated HCO3
- and is exported across the basolateral membrane via a Cl- channel. |
|
|
Term
| Stimuli for renin release |
|
Definition
1) Vascular baroreceptors. The arterioles of the JGA are innervated by renal sympathetic nerve fibers. Stimulation of these nerves activates beta1- adrenergic receptors on granular cells, which stimulates the release of renin through cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)-dependent signaling.
2) Intrarenal baroreceptors. Granular cells deform in response to changes in afferent arteriole pressure. Increases in renal perfusion pressure cause decreases in the secretion of renin. The opposite is also true.
3) Juxtaglomerular apparatus. Decreased Na+ delivery to the macula densa increases renin release. Increased Na+ delivery (based on concentration and flow rate) results in increased NaCl uptake by macula densa cells and inhibition of renin release |
|
|
Term
Aldosterone: Stimulation of Sodium
Reabsorption |
|
Definition
| stimulates sodium reabsorption in the collecting duct by regulating the number and open probability (Po) of epithelial sodium channels (ENaC) in the apical membrane of principal cells. Triamterene and Amiloride, a mild potassium sparing diuretic, directly blocks ENaC, while spironolactone, acts as an aldosterone antagonist |
|
|
Term
| The steps involved in aldosterone stimulation of sodium reabsorption |
|
Definition
1. Aldosterone crosses the basolateral membrane and binds to its receptor.
2. Once bound to its receptor, the aldosterone/receptor complex is transported into the nucleus then stimulates transcription of many genes but primarily that of serum glucocorticoid kinase 1 (sgk1).
3. Sgk1 does three things to simulate sodium reabsorption: A) stimulates membrane vesicles containing ENaC to be inserted into the apical membrane; B) inhibits Nedd4.2- dependent removal of ENaC from the apical membrane; and C) stimulates phosphoinositide kinase 3 (PI3K)-dependent increase in ENaC open probability (Po). |
|
|
Term
| Actions of atrial natriuretic peptide |
|
Definition
ANP antagonizes the effects of renin-angiotensin II-aldosterone. ANP
causes afferent arteriole vasodilation, inhibits renin, ADH and aldosterone secretion, and reduces the activity of renal sympathetic nerves. In addition to reducing levels of these factors which favor salt and water reabsorption, ANP also increases GFR and inhibits collecting duct Na+ reabsorption. |
|
|
Term
| Regulation of cellular uptake of potassium |
|
Definition
Epinephrine action on 2 receptors decreases plasma potassium by promoting cellular uptake of potassium.
Insulin decreases plasma potassium by stimulating cellular uptake. This results from an increase in Na+/K+-ATPase activity and is independent of glucose transport. A bolus of glucose along with insulin is commonly used to correct hyperkalemia; the glucose is given to prevent insulin-induced hypoglycemia.
Cell lysis leads to hyperkalemia. This often occurs as a result of severe trauma, tumor lysis syndrome and rhabdomyolysis (destruction of skeletal muscle which can result from drug ingestion, alcoholism, coma, or certain infections).
Aldosterone decreases plasma potassium by stimulating cellular uptake. Remember, this is at the level of the cell and not the kidney. Aldosterone has a greater affect on external K+ balance via its renal actions.
Metabolic acidosis increases plasma potassium.
Metabolic alkalosis decreases plasma potassium.
Hyperosmolality increases plasma potassium. |
|
|
Term
| External regulatiom of K+ |
|
Definition
| The PCT and TAL reabsorb most of the filtered K+. K+ can be reabsorbed or secreted in the distal tubule and collecting duct (alpha-intercalated cells reabsorb K+, while principal cells secrete K+). |
|
|
Term
| Regulation of Potassium by the Kidneys |
|
Definition
| 85% reabsorbed by PCT and TAL, so the majority that is lost is through secretion 50% by distal tubule and 30% by CD. |
|
|
Term
|
Definition
In the proximal tubule it starts by paracellular transport through tight junctions, as it moves distally a electrochemical gradiant favors K+ movement across the epithelium. Cells of the descending thin limb secrete K+ via the paracellular pathway. The
thick ascending limb reabsorbs K+ via both the paracellular and transcellular routes. Paracellular absorption is driven by the lumen-positive potential. Transcellular K+ absorption occurs via activity of the furosemide-sensitive transporter. During conditions of K+ depletion, cells of the collecting duct function to reabsorb K+ via a transcellular pathway. On the apical membrane, a K+ pump called the H+/K+-ATPase moves K+ into the cell coupled with H+. |
|
|
Term
|
Definition
| Cells of the TAL also express K+ channels on the apical membrane (ROMK channels). K+ secretion functions to recycle some of the K+ being absorbed by the furosemide-sensitive transporter to the lumen so that luminal K+ concentration does not fall low enough to inhibit Na+ and Clabsorption. |
|
|
Term
|
Definition
| Occurs in the DT and more in the CD. Apical membrane has more K channels and a stronger E gradiant then basolateral membrane. occurs through both K+ channels and a KCl cotransporter. |
|
|
Term
| Regulation of Renal Potassium Excretion |
|
Definition
Hyperkalemia stimulates excretion by activating tubular uptake by the Na+/K+
ATPase, which increases the driving force for potassium efflux across the apical membrane via potassium channels. This in turn stimulates aldosterone secretion whichstimulates increased cellular uptake of potassium by increasing the activity of the Na+/K+-ATPase, increasing the number of transporters (short-term) and increasing gene expression of Na+/K+-ATPase (long-term).
Furthermore, aldosterone increases the
potassium permeability of the apical membrane by increasing the number of potassium channels (short-term) and increasing gene expression of potassium channels (long-term). Increased tubular flow rate alos increases secretion. Acidosis reduces potassium secretion and excretion by inhibiting the Na+/K+-ATPase. Alkalosis has the opposite effect of acidosis. Increased tubular sodium concentration stimulates potassium secretion. Sodium reabsorption activates the Na+/K+-ATPase, this will increase potassium uptake, thereby increasing the driving force for potassium secretion. |
|
|
Term
| FE of Na (know this equation) |
|
Definition
(U[Na]/P[Na])/(U[Cr]/P[Cr]), get it when BUN:Cr is up and AKI is suspected
< 1.0% in prerenal azotemia
> 1.0% in ATN |
|
|
Term
|
Definition
(a) Intravenous non-nephrotoxic radionuclides
(b) Useful for Renal artery stenosis, Collecting system obstruction, Differential blood flow and function of bilateral kidneys |
|
|
Term
| Carbonic Anhydrase inhibitors |
|
Definition
(acetazolamide)
1) Mechanism of action ‐ increases urinary bicarbonate, potassium,
and water excretion. Effectiveness reduced when plasma bicarbonate concentration falls.
2) Pharmacokinetics ‐ weak diuretic, t1/2 ~ 13 hr
3) Toxicity ‐ metabolic acidosis and hypokalemia
4) Indications
1) Treatment of glaucoma or increased CNS pressure, although now used
relatively infrequently
2) Urine alkalinization
3) Prevention of altitude sickness
5) Contraindications ‐ liver failure (increases blood NH3 levels) |
|
|
Term
| Loop Diueretics names and mechanism of action. |
|
Definition
Furosemide, bumetanide and ethacrynic acid. Block Na/K/2Cl co‐transporter in TAL
– Decreases urine concentrating and diluting ability
– Increases water, K, Ca, Na and Mg excretion
– Vasodilator |
|
|
Term
| Loop diuretics toxicities |
|
Definition
– *Hypokalemia
– *Volume contraction
– *Calcium and magnesium depletion
– Ototoxicity (sulfonamides) ‐ ethacrynic acid no longer used |
|
|
Term
| Loop diuretics indications |
|
Definition
– Hypertension
– Acute diuresis needed
– Conditions refractory to less potent diuretics
• Congestive heart failure
• Renal insufficiency
• Nephrotic syndrome
– Hypercalcemia |
|
|
Term
| Loop diuretics contraindications |
|
Definition
– Patients susceptible to volume depletion (e.g. elderly)
– Patients susceptible to hypokalemia toxicity (digitalis, hepatic cirrhosis) |
|
|
Term
| Thiazide diuretics Mechanism of action and pharmokinetics |
|
Definition
‐ inhibits NaCl transport in
cortical TAL and distal tubule
– Milder diuretic action than loop diuretics
– Usually ineffective in severe renal insufficiency
– Volume contraction
• Enhances proximal tubule fluid and solute reabsorption
• Used to reduce stone formation by reducing calcium and uric acid excretion
• Pharmacokinetics
– Well absorbed from gut
– Onset of action in 1 hr, lasts 6‐48 hr |
|
|
Term
| Thiazide diuretics Indications and contraindications |
|
Definition
• Indications
– Hypertension
– Mild CHF
– Reduce stone formation
• Contraindications
– Cautiously used in patients susceptible to:
• Hypokalemia
• Hyperuricemia (gout)
• Hypercalcemia |
|
|
Term
|
Definition
• Quinazoline diuretic
• Same sites of action and side effects as thiazides
• Often given in more advanced renal
insufficiency, but other thiazides may be equivalent
• Typically given with loop diuretic |
|
|
Term
| Spironolactone MOA and pharmokinetics |
|
Definition
– Mechanism of action ‐ competitive aldosterone antagonist
• Inhibits Na reabsorption, and K and H excretion in late distal
tubule and collecting duct
• Reduces ammoniagenesis
• Antiproliferative/fibrogenic effect
– Pharmacokinetics
• Given orally
• Takes up to 2 days to be effective
• Only diuretic acting through blood side of tubule
• Relatively weak diuretic |
|
|
Term
| Spironolactone toxicities |
|
Definition
– Hyperkalemia
– Gynecomastia and amenorrhea |
|
|
Term
| spironolactone indications and contraindications |
|
Definition
• Indications
– Primary hyperaldosteronism
– Secondary hyperaldosteronism (cirrhosis)
– Reduces cardiovascular mortality in CHF likely through
non‐diuretic effects
• Contraindications ‐ in setting of hyperkalemia |
|
|
Term
|
Definition
| Same as spironolactone but without estrogen like side effects. Pricy$$$ |
|
|
Term
| Amiloride and triamterene |
|
Definition
• Mechanism of action
– Inhibits apical Na channel in late DT and collecting duct
– K+ and H+ secretion reduced
• Pharmacokinetics ‐ given orally, weak diuretic
• Toxicity
– Hyperkalemia
– Metabolic acidosis
– Nausea and vomiting
• Indications
– K+ sparing, often given with another diuretic
• Contraindications ‐ setting of hyperkalemia |
|
|
Term
|
Definition
| pH = ‐log([H+]) = pKa + log([A‐]/[HA]) |
|
|
Term
|
Definition
Arterial Blood Gas:
pH 7.4 (7.35‐7.45)
[H+] 40 (35‐45) nmol/L or neq/L
PCO2 40 (35‐45) mm Hg
[HCO3‐] 24 (22‐26) mmol/L or mEq/L
Plasma Electrolytes
[Na+] 140 (135‐145) mEq/L
[K+ ] 4 (3.5‐5.0) mEq/L
[total CO ] 26 24 30) 2(24‐mEq/L
[Cl‐] 100 (96‐109) mEq/L |
|
|
Term
|
Definition
| [ H+] = 24 × pCO2/[HCO3-] |
|
|
Term
| [H+] in nEq/L for common pH values |
|
Definition
7.60~25
7.50~30
7.40 =40
7.30~50
7.20 ~63 |
|
|
Term
|
Definition
| [Na] - ([Cl] + [HCO3]) normal range is 10 +/- 2 |
|
|
Term
|
Definition
• Osmolar Gap = Measured Posm – Calculated Posm.
• Osmolar Gap >= 25 indicates that there is a significant concentration of an osmotically active molecule. |
|
|
Term
|
Definition
| Posm = (2 × [Na+]) + [Glucose]/18 + [BUN]/2.8 |
|
|
Term
DIFFERENTIAL FOR METABOLIC ACIDOSIS WITH AN ELEVATED ANION GAP AND NORMAL
OSMOLAR GAP |
|
Definition
• Diabetic ketoacidosis
• Lactic acidosis
• D‐lactic acidosis
• Salicylate ingestion
• Renal failure (Severe) |
|
|
Term
| When to diagnose Diabetic Ketoacidosis |
|
Definition
| hyperglycemia, metabolic acidosis with an anion gap, and ketones in the blood and urine |
|
|
Term
| How to confirm Lactic Acidosis |
|
Definition
| Lactate and pyruvate levels can be measured rapidly to confirm a diagnosis of lactic acidosis. |
|
|
Term
|
Definition
| -Overgrowth of the small bowel with abnormal organisms result in the conversion of carbohydrates to D‐lactic acid. |
|
|
Term
| DIFFERENTIAL DIAGNOSIS OF METABOLIC ACIDOSIS WITH AN ELEVATED ANION GAP AND INCREASED OSMOLAR GAP. |
|
Definition
• Ethylene Glycol Ingestion
• Methanol Ingestion
• Alcoholic Ketoacidosis |
|
|
Term
|
Definition
• UNC = ((Urine [Na+] + Urine [K+]) – Urine [Cl‐])
• When the UNC is negative (Cl‐ > Na+ + K+), there is excretion of NH4+.
• With acidosis, the UNC is usually is ‐20 to ‐50 mEq/L.
• When the UNC is positive (Na+ + K+ > Cl‐), there is impaired excretion of NH4+.
• NH4+ excretion can be impaired with certain kidney diseases. |
|
|
Term
| DIFFERENTIAL FOR METABOLIC ACIDOSIS WITH A NORMAL ANION GAP |
|
Definition
• Renal causes
– Renal tubular acidosis (RTA)
• Distal or type I RTA (dRTA)
• Proximal or type II RTA (pRTA)
– Fanconi’s syndrome
• Generalized nephron dysfunction or type IV RTA
– Mild Renal failure
• Non‐renal causes
– Gastrointestinal HCO3
‐ loss
– Total parenteral nutrition
– Dilutional acidosis |
|
|
Term
| Gastrointestinal HCO3- loss |
|
Definition
METABOLIC ACIDOSIS WITH A NORMAL ANION GAP
– Diarrhea
– External pancreatic drainage (transplant or pancreatitis)
– Small bowel drainage (ileostomy). |
|
|
Term
| Total parenteral nutrition (TPN) |
|
Definition
| METABOLIC ACIDOSIS WITH A NORMAL ANION GAP. |
|
|
Term
METABOLIC ALKALOSIS
• Renal Causes |
|
Definition
‐ Urine [Cl‐] is high ( > 10 mEq/L)
– Diuretics
– Bartter’s syndrome
– Gitelman’s syndrome |
|
|
Term
|
Definition
| Urine [Cl‐] is low ( < 10 mEq/L) |
|
|
Term
|
Definition
| Urine [Cl‐] is low ( < 10 mEq/L) |
|
|
Term
METABOLIC ALKALOSIS
Non‐renal causes |
|
Definition
Urine [Cl‐] is low ( < 10 mEq/L)
-Gastrointestinal losses of H+
-Contraction alkalosis
-Post‐hypercapneic alkalosis |
|
|
Term
|
Definition
Loss of bicarbonate free or chloride
containing fluid from extrarenal source.
-Causes
-Excessive gastric secretion (achlorhydria)
-Excessive sweat (cystic fibrosis)
-Rare forms of secretory diarrhea due (villous adenoma, laxative abuse or congenital
chloridorrhea). |
|
|
Term
Glomerulopathies Commonly Causing the
Nephrotic Syndrome. Others can also cause it but these pretty much always do. |
|
Definition
Diabetic Nephropathy,
Minimal Change Disease,
Focal and Segmental Glomerulosclerosis,
Membranous Nephropathy |
|
|
Term
| Erythrocyte casts occur solely in the glomerular disease and in two specific categories of glomerular disease: |
|
Definition
| (1) proliferative glomerulonephritis, and (2) inherited defects of type IV collagen, such as thin basement membrane disease and Alport syndrome. |
|
|
Term
| Presentation of Adult onset polycystic kidneys (Dominant) |
|
Definition
With pain, hematuria, hypertension, & slowly progressive renal failure. Often develop renal failure at about age 40 to 60, but can rarely present in the young and very old.
Associated lesions: Cerebrovascular berry aneurysms, which are fatal in ~10% of patients. Liver cysts are present in 40% of patients, but they are not clinically significant. Might have increased risk of developing renal cell carcinoma. |
|
|
Term
| Renal cell carcinoma occurance |
|
Definition
| accounts for 80-90% of all renal malignancies and ~2% of all malignancies in adults. It is more common in smokers, males, analgesic abusers, leather workers, and those exposed to asbestos or cadmium. It is also more common in the obese and is rare under the age of 40. common in von Hippel Lindau syndrome. |
|
|
Term
| Renal cell carcinoma presentation |
|
Definition
| Vary - painless hematuria with dull flank pain and chronic fever is classic. More often is clinically silent until the tumor becomes a large, painful flank mass, or with systemic symptoms such as weight loss, fever, or weakness. Occasionally polycythemia or other endocrine symptoms (hypercalcemia, hypertension, hepatic dysfunction, sex steroid secretion, & others) are present. |
|
|
Term
| Renal Cell Carcincoma Pathology |
|
Definition
Gross: The tumors are usually round, yellow to grey-white and can have hemorrhage, necrosis, and cysts.
Microscopic: Renal cell carcinomas are vascular tumors with solid, papillary, or tubular areas. The cytoplasm can be eosinophilic (with many mitochondria) or clear 80% (with abundant lipid or glycogen). |
|
|
Term
|
Definition
| defined by some as histologically similar to renal cell carcinoma but less than 2.5 or 3 cm in diameter. Others define adenomas as papillary tumors less than 1 cm in diameter, since metastases can occur (rarely) from tumors 1 to 3 cm in diameter |
|
|
Term
|
Definition
| can be large but have bland nuclei, abundant granular pink cytoplasm, and uniformly abundant mitochondria. They have some of the same histologic features as renal cell carcinomas, but have an excellent prognosis. |
|
|
Term
|
Definition
| uncommon benign tumors with abundant vessels, smooth muscle, and adipose tissue. While the majority of cases are sporadic, angiomyolipomas are very common in patients with tuberous sclerosis |
|
|
Term
|
Definition
| (also called nephroblastoma) is an embryonal tumor which recapitulates much of the renal structure. It is most common in 2-3 year olds, but is almost never present at birth. It can occur in older subjects. It must be distinguished from two less common, more aggressive pediatric renal tumors - clear cell sarcoma and rhabdoid tumor. |
|
|
Term
|
Definition
| most common congenital renal tumors (i.e. those that are found at birth). These spindle cell tumors are usually benign. |
|
|
Term
| Malakoplakia and Xanthogranulomatous cystitis |
|
Definition
| chronic infection which usually involves the kidney or lower urinary tract, often in the presence of obstruction. It is an inflammatory infiltrate with many macrophages and small calcified bodies (Michaelis-Guttman bodies). It is probably an abnormal tissue reaction to bacterial infection, usually a coliform gram-negative rod. Xanthogranulomatous cystitis is similar but lacks Michaelis-Guttman bodies. |
|
|
Term
|
Definition
| causes strictures (narrowing/stenosis), obstruction, hydronephrosis, and urothelial tumors, mainly squamous carcinomas. Eggs are found in concentrated urine, and have a terminal spine |
|
|
Term
| Transitional cell carcinoma |
|
Definition
| muscle invasion by the tumor is the most important factor determining prognosis and treatment, most common urothelial malignancy, is most common in males over the age of 50, and is associated with smoking and carcinogens used in dye, rubber, leather, paint, and organic chemical industries. Transitional cell papillomas and papillary urothelial neoplasms of low malignant potential are small, very well-differentiated tumors without invasion or thickening of the transitional epithelium. |
|
|
Term
|
Definition
| most common bladder neoplasm in children |
|
|
Term
|
Definition
| The prostate is enlarged and tender and there is low back pain, dysuria, and frequency. Prostatic massage reveals leukocytes. Biopsies (rarely done unless carcinoma is suspected) show variable numbers of granulocytes in the prostatic lumina and chronic inflammatory cells surrounding the ducts and glands. |
|
|
Term
| PSA findings that make Cancer likely |
|
Definition
| Rapidly rising PSA (more than 0.75 µg/L per year). Free PSA <12% indicates a high probability of carcinoma, while free PSA >30% indicates a low risk for carcinoma. |
|
|
Term
| What type of stones form in an alkaline urine |
|
Definition
| Ca-phosphate due to distal renal tubular acidosis or hyperparathyroidism or alkali therapy. Triple phosphate and struvite stones from infections are alos formed in a high pH |
|
|
Term
| Which stones form in an acidic urine |
|
Definition
|
|
Term
| What are the shapes of the different stones? |
|
Definition
Struvite- coffin lid
Ca phosphate- amorphous sludge or wedge shaped stellate crystals
Cystine - Hexagonal
Uric acid - Amorphous or rhombic
Ca Oxalate - monohydrate are biconcave or dumbbell, dihydrate are octahedral/bipyramidal |
|
|
Term
|
Definition
| Stone occupies and obstructs clayces and pelvis. Most common w Struvite and Cystine, less common uric acid |
|
|
Term
|
Definition
| Uric acid or xanthine stones, treat both w allopurinol |
|
|
Term
| What size of stones are unlikely to pass |
|
Definition
|
|
Term
| What are some of the normal inhibitors of stone formation |
|
Definition
| Mg forms a soluble complex with oxalate and citrate chelates Ca in a soluble complex |
|
|
Term
| Onset of stones before puberty suggets what |
|
Definition
| Distal renla tubular acidosis, primary hyperoxaluria, cystinuria |
|
|
Term
| Onset of stones in third decade suggests what |
|
Definition
males- idiopathic Ca and uric stones
females - Struvite and hyperparathyroidism |
|
|
Term
| Treatment of stones caused by hyperuricosuria alone or in combo w hyper calciuria |
|
Definition
| Allopurinol and low protein diet |
|
|
Term
| Treatment of stones due to hypocitraturia |
|
Definition
|
|
Term
| Treatment of stones due to primary hyperparathyroidism |
|
Definition
| Orthophosphate if hypercalcemia is not severe. |
|
|
Term
| Treatment of stones due to Distal tubular renal acidosis |
|
Definition
| Sufficient alkali, K bicarb or K citrate |
|
|
Term
| Treatment of stones due to hyperoxaluria |
|
Definition
| reduce dietary excess, possibly use CaCO3 (may cause hypercalciuria). If ineffectinve use Cholestyramine or Al(OH)3 |
|
|
Term
| Treatment of stones due to uric acid stones |
|
Definition
| Treat underlying disease and and alkalize urine. High fluid intake, reduce dietary purines. Allopurinol if high UA excretion. Acetazolamide and Na bicarb can alkalize urine |
|
|
Term
| Treatment of stones due to Cystine |
|
Definition
| Surgical removal of staghorn calculi, lithotripsy for small stones. Vigorous hydration, urinary alkalization. D-penicillamine to form soluble complexes |
|
|
Term
| Treatment of struvite stones |
|
Definition
| Surgically remove staghorn calculi, ESWL if urine is sterile. Antimicrobials if bacteia is cultured. |
|
|
Term
|
Definition
• Collecting duct ectasia; always with congenital
hepatic fibrosis
• Neonatal mortality from pulmonary hypoplasia
• Risk of portal hypertension (GI bleeding), systemic
hypertension, renal failure |
|
|
Term
| Juvenile Nephronophthisis |
|
Definition
• Presentation: concentrating defect, anemia, poor growth, hypertension unusual in childhood unless renal function seriously impaired
• Histology: sclerosing tubulointerstitial disease
• Autosomal recessive; Tapetoretinal degeneration, hepatic fibrosis, skeletal
anomalies, mental retardation may be seen |
|
|
Term
|
Definition
| prototypic lysosomal membrane transport disease. The disulfide amino acid cystine acculmulates within cellular lysosomes, resulting in crystal formation and cell death in various tissues. Fanconi syndrome, severe photophobia due to corneal crystals, hypothyroidism, and to experience severe growth retardation. It is now treated with cysteamine, which forms a mixed disulfide with cysteine. |
|
|
Term
|
Definition
• Insoluble oxalate crystals deposit in the kidney, metaphysis, myocardium, arteries
• Severity is variable; may result in ESRD in infancy vs. stones in adults
• Different enzyme deficiencies different phenotypes |
|
|
Term
|
Definition
• X-linked dominant (Alport’s syndrome) (85%)
– Kidneys, ears often, eyes occasionally
– COL4A5 mutations; lack of GBM
component
– Males often more severely affected
– Hematuria in children
– Onset of renal failure usually in
adulthood; variable timing and
severity |
|
|
Term
| Posterior Urethral Valves |
|
Definition
• Most common bladder outlet obstruction in pediatric males
• Mechanical obstruction increased
urinary tract pressure thick walled
bladder
• One way obstruction at the prostatic
urethra
• Often associated with VUR; may be
associated with renal dysplasia |
|
|
Term
| Prune Belly Syndrome (Eagle-Barrett) |
|
Definition
| • Triad: deficient abdominal musculature, bilateral cryptorchidism, dilated “nonobstructed” urinary tract |
|
|
Term
|
Definition
| mainly a renal vascular disease. Some of the small renal arteries / arterioles become stenotic, with a renin / angiotensin / aldosterone response. It is most likely to occur in patients with relatively few glomeruli. Kidneys are also a principal target for hypertension-induced damage, causing feedback cycles of worsening hypertension. |
|
|
Term
|
Definition
| Renal involvement is seen in 2/3 of the patients. The most prominent findings are in the wall of interlobular arteries. When affected, they have intimal thickening with mucinous or finely collagenous material. They stain as mucopolysaccharides and glycoproteins. There is also concentric hypertrophy of the medial layer resembling the changes of malignant hypertension. |
|
|
Term
| Type of nephritis produced by small vessel vasculitis (Wegeners) |
|
Definition
| crescentic, ANCA-associated, pauci-immune glomerulonephritis |
|
|
Term
|
Definition
| rare cause of hypertension (2-5% of cases). most common cause is atherosclerotic plaque (70%). A different lesion, more common in young females, is fibromuscular dysplasia of the renal artery |
|
|
Term
|
Definition
| occurs most often in association with the nephrotic syndrome, in cases of dehydrated infants, and in cases of renal trauma/compression. Renal vein thrombosis is most common in cases of membranous glomerulonephritis. Acute cases present with flank pain, hematuria, and rapid deterioration of renal function. However, a majority of cases present with chronic obstruction and are asymptomatic. |
|
|
Term
|
Definition
– Red Cell - Proliferative GN or GBM defect
– RTEC - Many types of renal disease
– WBC - Intrarenal infection or inflammation
– Granular - Many types of renal disease
– Hyaline - may be normal unless numerous
– Waxy - Chronic renal disease |
|
|
Term
|
Definition
• An important correctable cause of renal failure.
• May be no symptoms, pain, nocturia.
• Stone, tumor, BPH, congenital causes.
• Hyperkalemia, acidosis, renal failure, HTN.
• Ultrasound best initial test.
• Relieve it soon, today if infected. |
|
|
Term
|
Definition
I - IgG and C3 along GBM and mesangium, subendothelial and mesangial deposits
II - Auto antibody to factor H, linear C3 along GBM and elongatted dense deposits in GBM.
Both I and II - Mesangial proliferation with basement membrane thickening and splitting, complement dysregulation |
|
|
Term
| renal disease, No proteinuria |
|
Definition
| Vascular diseases, obstruction |
|
|
Term
| Liver failure increases or decreases urea production |
|
Definition
|
|
Term
| When effective arterial blood volume is reduced, which one of the following (assuming normal kidney function) MUST be true? |
|
Definition
| Renal perfusion is reduced |
|
|
Term
| During a water diuresis, the osmolality of the medullary interstitium is |
|
Definition
| Much higher than plasma (over 400 mOsm/kg). The renal medulla remains strongly hypertonic to plasma in all states of hydration. The medullary gradient may wash out to some degree during water diuresis, but the medulla still remains well above blood osmolality. |
|
|
Term
| Differentiate between polydipsia and nephrogenic DI |
|
Definition
| Polydipsia has hyponatremia |
|
|
Term
| Treatment of symptomatic SIADH |
|
Definition
Hyertonic Saline. V2 receptor antagonism or water restriction will help, but since she is acutely
symptomatic, treatment with hypertonic saline is indicated. |
|
|
Term
|
Definition
|
|
Term
Which of the following is not an emergency treatment for hyperkalemia?
A. Intravenous insulin and glucose
B. Inhaled beta-agonists
C. Intravenous aldosterone
D. Intravenous sodium bicarbonate |
|
Definition
|
|
Term
| Potassium secretion in the distal tubule is increased by intravenous infusion sufficient to produce pharmacologic (i.e. above physiological) levels of |
|
Definition
|
|
Term
An 80 year old man with a 2 year history of nocturia three times a night is hospitalized for a myocardial infarction. He has no history of prior renal disease and is not diabetic. His BP has been repeatedly normal on annual visits and is now 170/110. He says he has no problems passing urine: “I go great , Doc. I pee like a horse – more than other people – there’s no problem there!” Urinalysis shows no blood, and trace protein. He has these lab values:
Na 140, K 6.8, Cl 120, HCO3 8 mEq/l, BUN 40, Creat 3 mg/dl.
The most likely renal diagnosis is:
A. Chronic glomerulonephritis
B. Hypertensive nephrosclerosis.
C. Nephrogenic diabetes insipidus
D. Obstructive uropathy
E. Surreptitious furosemide therapy |
|
Definition
| There are many clues in the history to obstruction: 2 years of nocturia, high urine volume, development of hypertension at a later age than expected for essential hypertension, hyperkalemia, acidosis, renal insufficiency, and minimal proteinuria. Chronic GN will give heavier proteinuria and likely edema and a longer history of hypertension. Hypertensive nephrosclerosis is untenable with no hypertension until the past year. NDI does not cause acidosis, hyperkalemia, or (commonly) renal failure. Surreptitious furosemide therapy could cause some features of high urine volume and nocturia and even the azotemia as a result of volume depletion, but it would also cause hypokalemia and alkalosis. |
|
|
Term
Which statement is true about renal blood flow and glomerular filtration rate around the time of birth.
A. Glomerular filtration rate increases rapidly at birth at any gestational age after 28 weeks.
B. Glomerular filtration rate reaches adult levels (per 1.73 m2) by 3 months postnatal life.
C. Glomerulogenesis is complete at 26 weeks gestation.
D. Renal blood flow is around 25% of cardiac output in the fetus.
E. Renal blood flow is directed primarily to the juxtamedullary region in the fetus. |
|
Definition
Before completion of glomerulogenesis at about 34 gestation, renal blood flow is low and mostly goes to the juxtamedullary region.
GFR increases rapidly after birth at term or after 34 weeks post-conception if birth occurs before 34 weeks.
GFR reaches adult values (per 1.73 sq m) by one year. So E. |
|
|
Term
| The most common cause of the Fanconi syndrome in children is: |
|
Definition
|
|
Term
| The risk of renal failure in patients with renal hypoplasia is related to |
|
Definition
| Degree of reduction of renal mass |
|
|
Term
|
Definition
| Water and penicillamine which binds with cysteine to yield a mixed disulfide which is more soluble than cystine. |
|
|
Term
A 17 year old diabetic patient is sent to your office because he has had hematuria noted on 3 routine physical exams over the past 3 years. Exam shows BP 140/88, normal fundoscopic exam, normal JVP, and no edema. His urinalysis shows 2+ blood, no protein and trace glucose; there were 20-50 dysmorphic erythrocytes/HPF and no other abnormality on microscopy. He most likely has:
A. Anti-GBM nephritis
B. Diabetic nephropathy
C. Focal segmental glomerulosclerosis
D. IgA nephropathy
E. Minimal change nephrotic syndrome. |
|
Definition
| Anti-GBM nephritis is a rare condition; it causes rapid renal failure but this patient has had his renal condition for 3 years or more. Diabetic nephropathy is first manifest by proteinuria (very first microalbuminuria), not hematuria. Focal segmental glomerulosclerosis and minimal change nephrotic syndrome give a nephrotic picture, not hematuria. IgA nephropathy often presents as chronic isolated microhematuria. (Note that diabetics don’t just get diabetic-related diseases. You aren’t expected to know this, but diabetics actually get more non-diabetic glomerulonephritis than do others in the population.) D. |
|
|
Term
| The most important pathogenic event in the development of diabetic nephropathy is |
|
Definition
| expansion of the glomerular mesangium. Thickening of the glomerular basement membrane also occurs but it does not correlate as well with loss of GFR. |
|
|
Term
| A viral illness is well known to be able to trigger a bout of macroscopic hematuria in |
|
Definition
|
|
Term
| Erythrocyte casts occur solely in |
|
Definition
| glomerular disease and in two specific categories of glomerular disease: (1) proliferative glomerulonephritis, and (2) inherited defects of type IV collagen, such as thin basement membrane disease and Alport syndrome. |
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Term
| This patient has metabolic alkalosis and hypokalemia. The usual causes of this combination are |
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Definition
| diuretics and vomiting. Diuretics are unlikely after a negative diuretic test. Vomiting is excluded by the presence of appreciable chloride in the urine: with vomiting, chloride is lost in the emesis and the urine becomes virtually free of chloride. Barrter's rises in likelihood when these two common causes are eliminated. |
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Term
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Definition
Fluoroquinolones
ciprofloxacin
levofloxacin |
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Term
| Treatment of Acute uncomplicated Cystitis in womaen: Escherichia coli, Staphylococcus |
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Definition
| 3-Day regimens: oral TMP-SMX, TMP , quinolone; |
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Term
| Treatment of Acute uncomplicated Cystitis in womaen:saprophyticus, Proteus mirabilis , Klebsiella pneumoniae |
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Definition
nitrofurantoin. Mitigating circumstances Diabetes, symptoms for >7 d, recent UTI, use of diaphragm, age >65 years then use Consider 7-day regimen: oral TMP-SMX, TMP, quinolone.
If pregnant: Consider 7-day regimen: oral amoxicillin, macrocrystalline nitrofurantoin, cefpodoxime proxetil, or TMP-SMXb |
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Term
| Treatment for Mild to moderate Acute uncomplicated pyelonephritis in women |
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Definition
| Oral c quinolone for 7–14 d (initial dose given IV if desired); or single-dose ceftriaxone (1 g) or gentamicin (3–5 mg/kg) IV followed by oral TMP-SMXb for 14 d |
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Term
| Treatment for severe Acute uncomplicated pyelonephritis in women |
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Definition
| Parenterald quinolone, gentamicin (± ampicillin), ceftriaxone, or aztreonam until defervescence; then oralc quinolone, cephalosporin, or TMP-SMX for 14 d |
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Term
| Complicated UTI in men and women |
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Definition
Mild to moderate: Oralc quinolone for 10–14 d
Severe:Parenterald ampicillin and gentamicin, quinolone, ceftriaxone, aztreonam, ticarcillin/clavulanate, or imipenem-cilastatin until defervescence; then oralc quinolone or TMP-SMX for 10–21 d |
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Term
| Which UTI drugs are contraindicated in pregnancy |
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Definition
| . Fluoroquinolones should not be used in pregnancy. TMP-SMX, although not approved for use in pregnancy, has been widely used. Gentamicin should be used with caution in pregnancy because of its possible toxicity to eighth-nerve development in the fetus. |
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Term
| Acute pyelonephritis in pregnancy |
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Definition
| managed with hospitalization and parenteral antibiotic therapy, generally with a cephalosporin or an extended-spectrum penicillin. Continuous low-dose prophylaxis with nitrofurantoin should be given to women who have recurrent infections during pregnancy. |
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Term
In the treatment of complicated urinary tract infection, while awaiting culture and sensitivity
results, what empiric antibiotic therapy is indicated for mild illness? Severe illness? |
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Definition
• In patients with minimal or mild symptoms, oral therapy with a fluoroquinolone, such as ciprofloxacin or levofloxacin, can be administered until culture results and antibiotic sensitivities are known. In patients with more severe illness, including acute pyelonephritis or suspected urosepsis, hospitalization and parenteral therapy should be undertaken
• Commonly used empirical regimens include imipenem alone, an extended-spectrum penicillin or cephalosporin plus an aminoglycoside, and (when the involvement of enterococci is unlikely) ceftriaxone or ceftazidime. |
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Term
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Definition
Calcium carbonate
Calcium acetate
Aluminum hydroxide
Aluminum carbonate
Sevelamer
Lanthanum carbonate |
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Term
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Definition
Calcitriol
Paricalcitol
doxercalciferol |
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Term
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Definition
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Term
A 24 year old female complains of 3 weeks of lower extremity, hand and facial swelling. She has a serum creatinine concentration of 0.7 mg/dl, a serum albumin concentration of 3.1 g/dl and a urine protein to creatinine ratio of 10 (equivalent to 10 grams of proteinuria per day). A renal biopsy reveals minimal change glomerulonephritis and you start her on prednisone. Which of the following statements is true about this patient?
A. Nephrotic syndrome consists of heavy proteinuria, hypoalbuminemia and hypernatremia.
B. Plasma volume is increased in nephrotic syndrome due to peripheral vasodilatation.
C. The hypoalbuminemia is the major cause of fluid retention.
D. Plasma volume is likely markedly contracted, as is typically found in patients with nephrotic syndrome.
E. The kidney has an intrinsic defect in renal Na excretion, so the response to diuretics may not be as large as in a healthy patient |
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Definition
Nephrotic syndrome consists of heavy proteinuria, hypoalbuminemia and hypercholesterolemia, not hypernatremia.
Plasma volume is frequently increased in nephrotic syndrome due to an intrinsic defect in renal sodium excretion.
Hypoalbuminemia can ultimately lead to edema formation, but the major cause of Na and water retention is an intrinsic defect in renal Na excretion. E. |
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Term
A 49 year old woman complains of high urine output. On a 24 hr urine collection, she has at least 4 liters of urine (though it is not known if the complete urine output was collected). Her serum osmolality is 250 mOsm/kg water and her urine osmolality is 180 mOsm/kg water. You would expect which of the following on testing?
A. A CT of the head would likely reveal a tumor or other space-occupying lesion in the region of her pituitary gland and/or hypothalamus.
B. Vasopressin administration would fail to cause any increase in her urine osmolality.
C. Water restriction would cause marked volume depletion due to continued excessive urinary fluid losses.
D. Water restriction would fail to cause any increase in her urine osmolality.
E. Water restriction would likely lead to a normalization of her serum osmolality over several days to weeks. |
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Definition
The patient has psychogenic polydipsia.
Water restriction would raise her urine and serum osmolality. It would not cause marked fluid losses, as there is no evidence of kidney disease.
A brain tumor might cause SIADH or central DI, neither of which fits this case.
Vasopressin would increase urine osmolality in a patient with psychogenic polydipsia or taking diuretics, though it may not maximally increase it E. |
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Term
A patient has the following results. Blood: pH 7.54, [H+] 29 nmol/L, pCO2 46 mm Hg, [HCO3-] 38 mmol/L, [Na+] 140 mmol/L, [K+] 2.5 mmol/L [Cl-] 84 mmol/L. Urine test results included pH 8.0 and [Cl-] 44 mmol/L. Which diagnosis is most plausible?
A. Diabetic ketoacidosis.
B. Diarrhea.
C. Diuretic treatment.
D. Renal tubular acidosis.
E. Vomiting. |
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Definition
| The [H+] is reduced, so the patient has alkalemia and diuretics and vomiting are the only possible choices. The presence of urine chloride excludes vomiting as a possibility. With vomiting, chloride loss in emesis reduces urine chloride to near zero. |
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Term
| Finnish-type congenital nephrotic syndrome |
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Definition
| severe inherited kidney disease caused by mutations in the nephrin gene. The slit pore membrane of the podocyte is abnormal. Massive proteinuria develops in the first few months and ESRD usually by age 3. |
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Term
| The most common cause of nephrotic syndrome associated with the use of NSAIDs is |
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Definition
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Term
| The most common cause of nephrotic syndrome associated with the use of NSAIDs is |
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Definition
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Term
Which of the following is TRUE regarding acute tubular necrosis (ATN)?
A. Fractional excretion of sodium (FENa) is typically lower than 1.0%.
B. Oliguria (less than 500 mL of urine per day) is essential for the diagnosis of ATN.
C. Substantial recovery in glomerular filtration rate is possible even after three weeks of oliguria
D. The presence of red blood cell casts in the urine is typical. |
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Definition
Fractional excretion of sodium (FENa) is typically lower than 1.0% in prerenal azotemia and greater than 1% in ATN.
Oliguria is common but not universal in ATN.
With the severity of multiple organ failure encountered nowadays, it is common for renal failure to persist for several weeks before recovery.
Red cell casts are characteristic of glomerular disease, not ATN. C. |
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Term
Which of the following is TRUE regarding acute tubular necrosis (ATN)?
A. Fractional excretion of sodium (FENa) is typically lower than 1.0%.
B. Oliguria (less than 500 mL of urine per day) is essential for the diagnosis of ATN.
C. Substantial recovery in glomerular filtration rate is possible even after three weeks of oliguria
D. The presence of red blood cell casts in the urine is typical. |
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Definition
Fractional excretion of sodium (FENa) is typically lower than 1.0% in prerenal azotemia and greater than 1% in ATN.
Oliguria is common but not universal in ATN.
With the severity of multiple organ failure encountered nowadays, it is common for renal failure to persist for several weeks before recovery.
Red cell casts are characteristic of glomerular disease, not ATN. C. |
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Term
Which of the following urinary findings is more typical of tubulo-interstitial than glomerular disease?
A. Dysmorphic erythrocytes.
B. Oval fat bodies.
C. Red cell casts.
D. Scant proteinuria. |
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Definition
| Dysmorphic erythrocytes, red cell casts, fat bodies, and heavy proteinuria are typical of glomerular disease. Typically interstitial nephritis displays sparse findings on microscopy, except perhaps for leukocytes, and there is scant proteinuria. D. |
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Term
A patient with nephrotic syndrome requests more diuretic. Which of the following is the best guide to whether an increase in dose of diuretic is appropriate.
A. Height of jugular venous pressure
B. Magnitude of proteinuria.
C. Serum albumin concentration.
D. Serum sodium concentration.
E. Severity of edema. |
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Definition
| The fullness of the circulation is the best guide to whether more diuretic is likely to work or whether it will be dangerous by worsening hypovolemia and attendant complications. A. |
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Term
A patient with serum creatinine 5.6 and BUN 28 mg/dl most likely has:
A. Acute tubular necrosis.
B. Corticosteroid therapy.
C. Gastrointestinal bleeding.
D. Hypovolemia.
E. Rhabdomyolysis |
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Definition
The BUN:creatinine ratio is low at 5. This implies either that creatinine is relatively high or urea is relatively low. Rhabdomyolysis liberates creatine from muscle and creatine will be converted to creatinine.
Acute tubular necrosis scarcely changes BUN:creatinine ratio.
Corticosteroid therapy and gastrointestinal bleeding both increase urea production and thus the BUN:creatinine ratio.
Hypovolemia raises the BUN:creatinine ratio because of enhanced tubular reabsorption of urea. |
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Term
A 14-year-old girl is seen for malaise. For two months, she has had fleeting joint pains and an erythematous rash on the hands, forearms, chest, and cheeks, but no sore throat. On exam, her BP is 135/90, she has 1+ edema and her urine contains 1+ protein and 3+ blood. On microscopy there are dysmorphic erythrocytes and red cell casts. Lab studies include creatinine 1.6 mg/dl, C3 30 mg/dl, and negative ASOT. The most likely diagnosis is:
A. Anti-GBM nephritis.
B. IgA nephropathy.
C. Membranous nephropathy.
D. Rapidly progressive glomerulonephritis.
E. Systemic lupus erythematosus |
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Definition
The joint pains, rash, renal disease, and low complement are all consistent with lupus.
Anti-GBM nephritis does not give joint pains, rash, or low complement.
IgA nephropathy does not give joint pains, rash, or low complement.
Membranous nephropathy gives a nephrotic, not a nephritic syndrome.
Rapidly progressive glomerulonephritis does not give joint pains, rash, or low complement. No information is given that suggests that renal function is declining quickly. E. |
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Term
An 17 year-old girl is found to have severe chronic renal failure. She has symmetrically shrunken kidneys on ultrasound and 3 grams/day proteinuria. VCUG confirms the diagnosis of vesico-ureteric reflux. What is the most likely explanation for the proteinuria?
A. Amyloidosis.
B. Focal segmental glomerulosclerosis
C. Membranous nephropathy.
D. Tubular proteinuria.
E. Urinary tract infection. |
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Definition
| Focal segmental glomerulosclerosis is the glomerular lesion that supervenes in a minority of cases of VUR. |
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Term
A 40 year old National Guard member has 3+ hematuria and 3+ protein discovered at an examination before redeployment to Iraq. The urine was clear yellow, and microscopy confirmed many red cells. Which is the most likely explanation.
A. Bladder tumor.
B. Focal segmental glomerulosclerosis.
C. Hemophilia.
D. IgA nephropathy.
E. The drop of blood from a finger stick that he added to the sample. |
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Definition
IgA nephropathy is the most likely explanation. It is a common form of glomerulonephritis and will cause both hematuria and proteinuria.
Focal segmental glomerulosclerosis causes heavy proteinuria, but usually little or no hematuria.
Bladder tumor, hemophilia, or a drop of added blood could account for the hematuria, but does not explain the proteinuria. Added blood from inside or outside the urinary tract will not register as protein unless the blood is easily visible to the naked eye.
You may wonder whether adding a drop of blood to a sample of urine would register as blood. It will easily. If a 0.05 ml drop of blood is added to 250 ml of urine, the dilution is 5,000x. If the blood RBC count is 5,000,000/µl, the RBC count in the urine will be 1000/µl, which corresponds to “TNTC” (too numerous to count) on microscopy. |
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Term
An 8 year old girl has had several urinary tract infections. Her mother had recurrent urinary tract infections and a sister has a unilateral duplicated urinary collecting system. Serum creatinine is 0.5 mg/dl (normal for age). Which imaging will most likely help establish a diagnosis?
A. Abdominal X-ray.
B. CT scan with contrast.
C. CT scan without contrast.
D. Renal sonogram.
E. VCUG. |
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Definition
| The history of recurrent UTIs suggests an anatomic abnormality, most likely reflux. Reflux is familial in 1/3 of cases, so the FH supports the diagnosis. VCUG is the only imaging that will establish a specific diagnosis. |
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Term
Two classes of proximal tubular secretion
mechanisms
• Acids = anions |
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Definition
– Most penicillins and cephalosporins
– Sulfonamides (includes loop and thiazide diuretics)
– NSAIAs
– Probenecid
– PAH
– Urate
– Phase 2 metabolism conjugates |
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Term
Two classes of proximal tubular secretion
mechanisms
• Bases = cations |
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Definition
– Morphine, histamine, quinine, amiloride,
neostigmine, ephedrine
– Creatinine, cimetidine, trimethoprim, triamterene |
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Term
Drugs can accumulate!
These drugs need major dose reduction |
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Definition
• Aminoglycosides.
• Vancomycin.
• Digoxin |
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