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289 Cards in this Set

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What percentage is the 60,40,20 rule?
TBW = 60% of total body weight
ICF = 40 % of total body weight
ECF = 20 % of total body weight (plasma is 1/4 of ECF, 1/12 of TBW)
3/4 is interstial fluid)
How do you measure TBW?
1. Titrated water
2. D20
How do you measure ECF?
1. Sulfate
2. Inulin
3. Mannitol
How do you measure plasma volume?
1. RISA
2 Evan's Blue
How do you measure ICF?
1. TBW-ECF
HOw do you measure interstitial volume?
1. ECF-Plasma volume
What are the 6 types of volume expansion and contraction?
How do they work?
1. Isotonic gain
2. Diarrhea Isotonic loss
3. NaCl intake Hyperosmotic gain
4.Sweating Hyperosmotic contractio
5. SIADH Hyposmotic expansion
6.Adrenocortico insuff (aldos insuff) NaCl loss. Hyposmotic contraction
What occurs in the syndrome of inappropriate ADH secretion in terms of volume?
What about Hct/Protein concentration?
1. Osmolarity of the ECF decreases because excess water is retained (hyposmotic volume expansion)
2. Fluid also moves into cells
3 Hct. stays the same, Protein concentration decreases
What occurs in adrenocortical insuff. in terms of volume?
1. Aldosterone is not produced and there is an excess excretion of Na/Cl
2. ECF becomes hyposmolar and fluid moves from the ECF into the ICF
3. Hct increases, protein concentration increases
what is the formula for renal clearance?
Clearance = U (mg/ml) V (ml/min)
P (mg/ml)
What is nephroptosis?
abnormally mobile kidneys that may move more than 3 cms
What is an ectopic kidney?
a congenitally misplaced kidney
How can you tell the difference between nephroptosis and an ectopic kidney?
in nephroptosis there is a coiled ureter
Where are transplanted kidneys place?
Illiac fossa
What are the anterior associations of the right kidney?
1. Liver
2. duodenum
3. ascending colon
What are the relations of the left kidney?
1. stomach
2. spleen
3. pancreas
4. duodenum
5. descending colon
what nerves run along the posterior surfaces of the kidneys?
1. iliohypogastic
2. ilioinguinal
What does inflammationin the pararenal area manifest intself as?
pain on extension of the leg (due to the location of the psaos major which flexes the thigh at the hip)
What is the surface anatomy of the ureters?
5cm lateral to L1 to the PSIS
Where are the three constrictions of the ureter?
1. at the renal pelvis
2. rim of the pelvic inlet
3. bladder
What is the occurrence and location of a horseshoe kidney?
1 in 600
level of L3-L5 (inf. messentaric vein does not allow to ascend)
When does a pelvic kidney pose a problem?
During child birth
What is the order of renal blood flow?
1 renal artery
2. interlobar artery
4 arcuate artery
4 interlobular artery
5. afferent arteriole
6. glomerulus
7 efferent arteriole
Remember the juxtamedullary nephrons have blood supply that divide into the vasa recta which empty into stellate veins
What is the formula for renal blood flow?
Q = Delta P
R
What causes vasoconstriction in the kidney?
Sympathetic output and angiotensin II (constricts efferent arterioles protecting GFR)
What affect to ACE inhibitors have on kidney function?
Dilate efferent arterioles and decrease GFR
This reduces the hyperfiltration seen diabetic nephropathy
What substances vasodilate renal arterioles?
1. prostaglandins E2/I2
2. bradykinin
3. NO
4. dopamine
At what pressures does autoregulation occur within the kidney?
80-200 mmHg
Explain the tuboglomerular Feedback mechanism
1 an increase in pressure causes an increase in NaCl concentration within the macula densa which is sensed and a signal is sent to the afferent arterioles to decrease GFR/RBF
What is the formula/technique for measuring renal plasma flow?
Clearance of PAH
Cpah = Urine [PAH] V
Plasma [PAH}
How do you measure renal blood flow?
RBF = renal plasma flow
1-hematocrit
How do you measure GFR experimentally and clinically
1. clearence of inulin
2. clearance of creatine
What is the filtration fraction?
Filtration fraction = GFR
RPF
What does an increase in the filtration fraction produce?
1. increase in protein concentration of peritubular capillary blood which leads to increase reabsorption in the proximal tubule
What does a decrease in the filtration fraction produce?
1. decrease in the protein concentration of the blood and a decrease of reabsorption in the proximal tubule
What happens to starlings forces during a kidney stone/constriction of the ureters?
There is an increase in the Pbs which decrease GFR.
What is Bowmans space oncotic pressure?
Usually 0 can be a sign of kidney failure
What affect does sympathetic acitivty have on GFR, RPF and FF?
1. decreases GFR, RPF with no change in filtration fraction
What affect does angiotensin II have on GFR, RPF and FF?
increases GFR, decreases RPF and increases filtration fraction
What affect does an increase in plasma protein have on GFR, RPF and FF?
decreases GFR (due to inc oncotic pressure), no change to RPF and a decrease in FF
What affect does a uretal stone have on GFR, RPF and FF (GFR/RPF)
Decreases GFR, no change to RPF and decreases FF
What is the formula for filtered load?
Filtered load = GFR x [plasma]
What is the formula for excretion?
excretion = V x [urine]
What is the formula for reabsorption?
Reabsorption = filtered load - excretion (if positive = net reabsorption)
Where is glucose reabsorbed? and to what degree?
1. proximal tubule
2. saturated at 350 mg/dL of blood (Tmax)
What is splay?
the region between 250 and 350 mg/dL of blood glucose explained by heterogeniety of nephrons and the low affinity of the Na glucose carrier
In an alkalotic urine what are the excreation rates of weak acids and weak bases?
1. In an alkalotic urine excretion of a weak acid is higher (negatively charged), example salycilic acid
2. weak bases the excretion rates are decreased due to back diffusion of the non polar B
In acidic urine what are the excretion rates of weak acids and weak bases?
1. weak acids excretion are decreased (HA) more back diffusion.
2. weak bases excretion rates are increased HB+, less back diffusion
In the proximal tuble what amount of Na+, Cl-, and K+ are reabsorbed?
67%
In the first half of the proximal tubule how is Na, Cl-, K+ and Ca2+ reabsorbed?
1. Na is reabsorbed via symporters with organic solutes (gluclose, amino acids, phosphate) and via a Na/H antiporter
2. Cl- is not reabsorbed
3. K+ and Ca2+ are reabsorbed via solvent drag through the paracellular pathway
In the second half of the proximal tubule how is Na, Cl-, K+ and Ca2+ reabsorbed?
1. Na is reabsorbed with a Na/H antiporter
2. Cl- has a high gradient because of the water loss in the first part and is reabsorbed via a Cl-/anion antiporter
3. H+ and the anion combined and are recycled by the cell
4. there is also a concentration gradient which pushes Cl- via the paracellular pathway along with Na.
5. K+ and Ca2+ also are reabsorbed via solvent drag.
What sets up the osmotic gradient in the lateral intercellular spaces for water osmosis?
1. the basolateral Na/K ATPase
In the proximal tubule what transporters exist on the basolateral membrane?
1. the Na/K ATPase
2. the Cl-/K+ symporter (out)
3. HCO3- uniporter (out)
4. Potassium channel.
5. GLUT
When giviing cimetidine one must be careful in administering which antiarrhythmic drug?
Why?
1.procainamide
2. they are excreted by the same organic cation channel in the proximal tubule
What can be given with pennicillin to decrease the rate of excretion from the kidney?
Para-aminohippuric acid because they have the same anionic channel in the proximal tubule.
What is fanconi's syndrome?
Renal disease that results in the impaired ability of the PT to absorbed amino acids, glucose and LMW proteins (aquired or genetic).
What is the Tamm=Horsfall Glycoprotein?
a normal protein secreted and appearing in the urine
In Henle's Loops where does the reabsorption of Na, Cl and K occur?
What percentage is it?
1. Thick ascending limb
2. 25 %
In the loop of Henle where is water reabsorbed and impermeable to?
1. In the descending thin limb
2. ascending parts are impermeable to water (sets up the hyposmolar urine for later concentration)
In the thick ascending limb, what sets up the Na gradient in the lateral intercellular space?
1. Na/K ATPase
What symporter is located in the Thick ascending limb?
1. Na/K/2Cl symporter (makes urine Hyposmolar)
What is Barter's Syndrome?
What causes it?
Autosomal recessive disorder characterised by:
1. hypokalemia
2. metabolic alkalosis
3. hyperaldosteronism (due to lowered ECV caused by decreased NaCl/K+ and water reabsorption)
4. Mutation in the Na/K/2Cl, apical K+transporter or the basolateral Cl- transporter in the thick ascending limb
What is furosemides action?
1. inhibits Na/K/2Cl symporter in the thick ascending limb
2. inhibits NaCl excretion
3. inhibits K and Ca2+ reabsorption by decreasing the lumens positive potential
What percentage of NaCl is reabsorbed by the distal tubule and collecting duct? How is it reabsorbed in the early distal convoluted tubule what about Ca2+?
1. 7%
2. Na/Cl-symporter
3. Ca2+ channels
How is NaCl reabsorbed in the late convoluted tubule and collecting duct (principle cells)?
1. Through Na Channels and Cl via paracellular
2.
What transporters are important on the basolateral membrane of the Distal convoluted tubule?
1. Na/K+ ATPase
2. Na (in)/Ca2+out symporter
What do principal cells reabsorb/secrete?
1. Na2+ via channels
2. Secrete K+ via channels
3. reabsorb water via aquaporin 2 (V2/ADH)
What do intercalated cells have on their apical membrane? Basolateral Membrane?
1. K in/H out antiporter
2. HCO03 out/ Cl- in antiporter
What are the actions of Amiloride?
1. K sparing diretic
2. works by blocking Na channels in luminal membrane of distal convoluted tubule/collecting ducts
3. Reduces the magnitude of negative charge and decreases K+ secretion and Cl- reabsorption
What are the 3 mechanisms of action of ACE inhibitors?
1. Decreases Na reabsorption in proximal tubule (Cl- and water indirectly)
2. decreases aldosterone secretion
3. decreases arterial BP by vasodilation
What is acetazolamides mechanism of action?
1. carbonic anhyrdrase inhibitor
2. acts as a diuretic in the early proximal tubule by inhibiting the reabsorption of HC03-
If the filtration fraction increases (GFR/RPF) what happens to oncotic pressure in the peritubular capillaries?
What is the net result?
1. there is an increase in oncotic pressure in the peritubular capillaries
2. there is an increase in reabsorption matching the increase in fluid filtrated
Why is atrial natriuretic peptide secreted?
What its action?
1. secreted in a response to increased ECF
2. It decreases total peripheral resistance
3. incrases NaCl and Water secretion by inhibiting their reabsorption in the medullary part of the collecting duct
4. inhibits ADH water reabsorption and inhibits ADH secretion from the P.P.
Why is urodilatins secreted where is it secreted and what are its actions?
1. secreted by the distal tubule and collecting ducts
2.Secreted in response to inc. in BP and ECV
i3. nhibits NaCl and H20 reabsorption by the collecting duct
What is dopamines action on the kidney? why is it release?
1. inhibits NaCl/H20 reabsorption from the proximal tubule
2. it is released in a response to an increase in ECV
What is the effect of sympathetic action (adren/noradren) on the kidney? Why is it released?
1. stimultes NaCl reabsorption from the proximal tubules, thick ascending limb, distal tubule and collecting duct
2. in response to a decrease in ECV
What does ADH do? What is its cellular pathway?
1. inserts aquaporin-2 in the distal convoluted tubule and collecting duct via the V2 receptor
2. V2 Gp activates adenylate cyclase, inc cAMP, inc. PKA, insertion of channels on apical membrane.
What stimulates the release of ADH?
1. increase in plasma osmolarity (SFO and OVLT)
2. decrease in BP
3. Nausea
4. Angiotensin II
Where is ADH produced and released from?
1. paraventricular and supra optic nuclei
2. post. pituitary
What inhibits ADH?
1. increase in BP
2. decrease in osmolarity
3. ANP
Where are low pressure receptors located? what do they response to?
1. Large pulmonary vesses and the Left atrium
2. overall vascular volume
What is neurogenic diabetes insipidus? What are the symptoms?
1. Loss of ADH secretion usually due to head trauma (can be genetic accumulation of preprohormone)
2. Polyuria/polydypsia
What occurs in the syndrome of inappropriate ADH secretion?
1. elevated ADH for blood pressure/osmolarity of plasma
2. concentrated urine
3. fluid retention
What is neurogenic diabetes insipidus? Whenis it iatrogenic? What type of genetic inheritance does it have?
1. does not respond to ADH
2. polydypsia/polyuria
3. 30-40% of people taking lithium have some degree of neurogenic diabetes insipidus
4. x linked
How is urine concentrated?
1. countercurrent multiplication
2. THINK ABOUT HOW IT WORKS
Where is aldosterone produced?
what is its action?
1. glomerulosa cells in the adrenal cortex
2. stimulates reabsorption of Na/Cl by the thick ascending limb, distal tubule and collecting duct by inserting Na channels (Cl indirectly by reducing the positive luminal charge)
3. Also increases potassium secretion
What are the characteristics seen in an ECG in a patient with hyperkalemia in order of increasing severity?
1. Tall thin T waves
2. Prolonged PR interval
3. depressed ST segment
4. P wave dissapears
5. QRS broadens
What are the characteristics seen in an ECG in a patient with Hypokalemia in order of severity?
1. prolongs QT interval
2. inverts T wave
3. lowers the ST segment
4. U wave
What hormones are important for the regulation of k+?
1. epinephrine
2. Insulin
3. aldosterone
How does epinephrine affect K+?
1. alpha receptors stimulate release of K+ especially from the liver
2. Beta 2 receptors stimulate K+ uptake
What affect does propranolol have on plasma K+ after a K+ rich meal?
Blocks B2 and causes a larger rise in K+ concentration after meals
what affect does stress have on plasma K?
Epinephrine release causes a rapid decrease in plasma K (e.g. MI)
Why does infusion of insulin (glucose) treat/prevent hyperkalemia?
What is seen in diabetics after a large K+ meal?
Insulin stimulates NaKATPase and the uptake of K into cells.
Diabetics have a higher K+ plasma after a K rich meal
Acidosis causes what change in plasma K?
What acids are more affective in causing this?
1. hyperkalemia
2. inorganic acids
Alkalosis causes what change in plasma K?
1. hypokalemia
What affect does plasma osmolality have on plasma K?
1. an increase in plasma osmolality increases plasma K because water leaves the cell and increases intracelluar K which drives K+ out of the cell.
2. vice versa for a decrease in osmolality
What does cell lysis cause?
What are three types of cell lysis pathologies?
1. Hyperkalemia
a. tumour cell lysis syndrome
b. rhabdomyolysis
c. gastric ulcer (RBC are lysed and K+ is absorbed)
When is exercised induced hyperkalemia potentially life threatening? Why?
1. endocrine def. in epinephrine, insulin, aldosterone
2. kidney failure
3. Beta blockers
Increase in k+ can cause cardiac arrhythmia
What drugs are responsible for hyperkalemia in the clinic?
1. K supplements
2. ACE inhibitors (decreases aldosterone)
3. K sparing diuretics
4. heprin
5. prostaglandin suppressing drugs that result in hypoaldosteronism
How much K+ is normally excreted in the urine? Where is K absorbed in a K deficient diet?
1. 90-95 percent
2. 67% in proximal tubule
3. 20 percent in thick ascending limb
4. 5 percent in DT
5. 9 percent in CD
Where is K secreted in a K rich diet?
1. 10-50 secreted in the distal tubule
2. 5-30 percent in the collecting duct
What occurs in terms of potassium in advanced renal disease?
What happens to the membrane potential and why?
1. hyperkalemia because it isn't excreted
2. decreases membrane potential membrane and reduces excitability byinactivating the fast Na+ channels
What affect do diuretics have on K?
1. Can cause hypokalemia (inc in urine flow)
2. hyperpolarises the membrane and decreases the excitability of the cell
How does aldosterone stimulate K+ excretion?
1. stimulates basolateral Na/KATPase activity (adds new transporters to membrane as well)
2. increases the permeability of the apical membrane to K+
What are four causes of hypokalemia?
1. diuretics
2. vomiting/nasogastric tube
3. diarrhea/laxitive abuse
4. hyperaldosteronism
1-3 stimulate aldosterone via volume contraction
What are 3 causes of hyperkalemia?
1. reduced urinary flow
2. decreased aldosterone levels
3. renal disease with a decrease of 20% in GFR
In the late distal tubule and collecting duct which cells are responsible for K secretion? How?
Reabsorption? How? When does this occur?
1. Principle cells (NaK ATPase sets up gradient, and apical K+ channel)
2. Alpha Intercalated Cell (K+/H+ antiporter)
3. Low potassium diets
What two factors determine Ca homeostasis?
1. total amount of Ca in the body (absorbed by GI/excreted by kidney)
2. Distribution of Ca in Bone/ECF
What hormone affects the total amount of Ca in the body?
1. calcitriol
2. stimulates Ca uptake in the GI and increases plasma Ca
What does Parathyroid hormone cause? How?
1. increases in plasma Ca
2. stimulates bone resorption via osteoblasts
b. stimulates Ca reabsorption from the kidneys by increases the activity of the Na (in)/Ca (out) ont he basolateral membrane in the distal convoluted tubule. Thereby increasing the gradient for Ca
b. Increases secretion of calcitriol by the proximal tubule cells
3. Increases phosphate excretion by inhibiting the Na/Phosphate cotransporter
WHen is calcitonin released? What affect does calcitonin have?
Where is it released?
1. In response to hypercalcemia
2. Stimulates bone formation
3. released from the parafollicular cells of the thyroid gland
What are the two most common types of hypercalcemia?
1. Primary hyperparathroidism tumour
2. Paraneoplastic syndrome with PTHL activity
10-20 percent of carcinoma (e.g. squamous cell lung cancer)
What affect does acidosis have on calcium?
1. causes an increase in the plasma concentration of caclium because H+ bind to complexes normally reserved for Ca
An individual with alkalosis is more susceptable to what problem concerning hypocalcemia?
1. hypocalemic tetani
What percentage of Ca is normally free for filtration?
55-60%
Where is Ca reabsorbed?
1. Proxmial tubule 80% paracellular and 20 % via Ca channels
2. Thick ascending Limb = paracellular
3. Distal convoluted tubule passivly via Ca channels (Ca/Na exchange on basolateral sets up gradient)
What is Gitelman's Syndrome?
What are the clinical characteristics?
1. Inactivating mut. of NaCl cotransporter in the distal tubule
2. causes increase in NaCl excretion
1. hypotension
2. hypokalemic metabolic alkalosis
3. hypocalciuria (decrease in renal excretion)
What is the distribution of phosphate?
1. 86% in the bone
2. 13 % in the ICF
3. .003 in the ECF
What stimulates Pi absorption in the GI?
Calcitriol
What affect does PTH have on plasma phosphate?
1. increases bone resorption and thus increases Pi in plasma
What affect does calcitonin have on Pi?
1. Decreases plasma Pi due to increased bone formation
How do kidneys reabsorb Pi? What affect does this have on excretion?
1. reabsorb Pi at maximal rate
2. an increase in Plasma Pi causes an increase in renal excretion
What occurs in chronic renal failure to cause osteititis fibrosa cystica?
1. Kidneys can't excrete Pi and GI absorption continues and plasma Pi increases
2. increases in Pi complexes with Ca and Ca concen in plasma decreases
3. Pi accumulation causes a decrease in calcitriol production and further decrease in Ca concn
4. causes a release of PTH and bone reapsorption causes osteititis fibrosa cystica
What is osteititis fibrosa cystica?
An oft complication of renal failure where there is an increase in PTH (due to low calcium levels) and increase in bone resorption and lost bone tissue is replaced with fibrinous tissue
What is the cause of metastatic calcifications?
What are some complications?
1. Chornic hyperparathroidism during chronic renal failure
2. Ca and Pi precipitate in artiers, soft tissue and viscera
3. myocardial failure, pulmonary insuff.
How does one treat chronic hyperparathroidism in chronic renal failure?
1. low Pi diet
2. give phosphate binder
3. supplemental Ca and calcitriol
What role does estrogen have in bone resorption?
defends against PTH induced bone resoprtion
If Tf/Px is greater than one?
Less than One?
Equal to one?
1. there is net secretion of there is more water reabsorption than solute
2.there is more solute reabsorption than water
3. there is no secretion or absorption or it equals water sec/abso
How does one measure water reabsorption?
Tf/Pinulin
Inulin is not secreted or filtered so as water reabsorption increases so does the Tf/Pinulin ratio
What is the fraction of Filtered H20 reabsorbed?
1-1
Tf/Pinulin
How much urea is passively reabsorbed through the proximal tubule?
1. 50%
What parts of the nephron are impermeable to urea?
1 distal tubule, cortical collecting ducts, outer medullary collecting ducts
What affect does ADH have on urea?
It increases the urea permability of the inner medullary collecting duct which contributes to urea recycling and the corticopapillary osmotic gradient
Where is magnesium reabsorbed?
In the proxmal tubule, thick ascending limb and distal dubule
What does hypermagnesimia cause?
Causes an increase excretion of Ca because they compete for reabsorption in the thick ascending limb
What is the formula for free water clearance?
Ch20 = V - Cosm

Cosm = Uosm x V
Posm
What is free water clearance when urine is hyperosmotic?
Hyposmotic?
Isosmotic?
1. negative
2. positive
3. zero
What is the stimulus for secretion for PTH?
What is the mechanism of Action?
1. decrease in plasma Calcium
2. basolateral receptor adenylate cyclase cAMP -->urine
What are the actions of PTH on the kidneys?
1. decraese phosphate reabsorption in the proximal tubules
2. increases Ca reabsorption in the distal tubles
3. stimulates 1alpha hydroxylase in proximal tubule
What is the function of 1 alpha hydroxylase?
cytochrome P450 enzyme in the proximal tubule which converts calcidiol to calcitriol (the bioactive form of Vitamin D).
How does PTH act on the TAL and Distal tubule
1. it stimulates the Na/Ca exchange on basolateral side
What are the stimulus for secretion of aldosterone?
1. decreased blood volume via angiotensin II
2. increased plasma K
What is the mechanisms of action?
New protein synthesis
What are the three actions that aldosterone has on the kidneys?
1. increases Na+ reabsorption of principle cells (Na/K ATPase on basolateral membrane)
2. Increases K secretion (via Na/K ATPase and increasing apical K+ permeability via K channels
3. Increase H+ secretion via the intercalated cells
What is the stimulation for secretion of ANP?
Increase in Atrial Pressure
What is its mechanism of action?
guanylate cyclase --> cGMP
what affect does it have on the kidneys?
1. increases GFR
2. decreases Na+ reabsoroption
What is the stimulus for secretion of Angiotensin II?
1. decrease in blood volume (sensed by the macula densa cells as a decrease in Na delivery) --> secrete reinin
What are the actions of Angiotensin II on the kidney?
What type of acid-base disturbance can this cause?
1. Increase the Na/H+ exchange and stimulate HCO3- reabsorption
2. Contraction alkalosis
What are the two types of acid produced in the body? What are they?
1. volitile acid (CO2)
2. non-volitile acid are fixed acids that are produced or ingested (eg. ketoacids, lactic acid, salicylic acid
When are buffers most effective?
when the pH is within 1.0 units of the pK
What is the major extracellular buffer?
What has a minor contribution?
1. HCO3-
2. Phophate (the pK of H2P04/HP04 is 6.8
What is the excretion of H+ as H2P04 in the urine called?
A titratable acid (explicitly excludes NH4)
What are the main intracellular buffers?
1. Organic phosphates (AMP, ADP, ATP, DPG)
2. Proteins Imidazole and alpha amino groups on proteins have pK's in physiologic ranges
3. deoxyhemoglobin
Where does reabsorption of filtered HC03- occur?
1. 80 percent is in the proximal tubule
2. 15% in the thick ascending limb
3. 5 percent in the distal tubule
How is HCO3 reabsorbed in the proximal tubule?
1. Na/H exchange. H+ into lumen combines with filtered HCO3-
2. carbonic anhydrase catalyzes to H20 + CO2 and is reabsorbed by cell
3. then CA inside the cell HCO3- (reabsorbed into plasma via the basolateral membrane) and H+ is secreted (does not result in net secretion)
What regulates the reabsorption of filtered HCO3-?
1. Filtered load (inc result in inc of reabsorption
2. PC02 increases in PC02 will cause an increase in reabsorption of HCO3- because there is more H+ available and vice versa (renal compensation along with inc/dec glutamine metabolism)
3. Inc/Dec in ECV result in decreases and increases in HCO3-
4. Angiotensin II results in increase Na/H exchanger and thus increases HCO3- reabsorption
What is the stimulus for secretion of Angiotensin II?
1. decrease in blood volume (sensed by the macula densa cells as a decrease in Na delivery) --> secrete reinin
What are the actions of Angiotensin II on the kidney?
What type of acid-base disturbance can this cause?
1. Increase the Na/H+ exchange and stimulate HCO3- reabsorption
2. Contraction alkalosis
What are the two types of acid produced in the body? What are they?
1. volitile acid (CO2)
2. non-volitile acid are fixed acids that are produced or ingested (eg. ketoacids, lactic acid, salicylic acid
When are buffers most effective?
when the pH is within 1.0 units of the pK
What is the major extracellular buffer?
What has a minor contribution?
1. HCO3-
2. Phophate (the pK of H2P04/HP04 is 6.8
What is the excretion of H+ as H2P04 in the urine called?
A titratable acid (explicitly excludes NH4)
What are the main intracellular buffers?
1. Organic phosphates (AMP, ADP, ATP, DPG)
2. Proteins Imidazole and alpha amino groups on proteins have pK's in physiologic ranges
3. deoxyhemoglobin
Where does reabsorption of filtered HC03- occur?
1. 80 percent is in the proximal tubule
2. 15% in the thick ascending limb
3. 5 percent in the distal tubule
How is HCO3 reabsorbed in the proximal tubule?
1. Na/H exchange. H+ into lumen combines with filtered HCO3-
2. carbonic anhydrase catalyzes to H20 + CO2 and is reabsorbed by cell
3. then CA inside the cell HCO3- (reabsorbed into plasma via the basolateral membrane) and H+ is secreted (does not result in net secretion)
What regulates the reabsorption of filtered HCO3-?
1. Filtered load (inc result in inc of reabsorption
2. PC02 increases in PC02 will cause an increase in reabsorption of HCO3- because there is more H+ available and vice versa (renal compensation along with inc/dec glutamine metabolism)
What are the causes of Respiratory acidosis?
1. Hypoventilation
-opiates, sedatives, anasthesia
-COPD (emphysema, chronic bronchitis, asthma, bronchiacstasis)
-Guellian-Barre syndrome, ALS, MS, polio (respiratory muscles fatigue)
-acute lung disease (ARDS, NRDS)
-airway obstruction
What are the causes of metabolic acidosis with a normal anion gap?
-Diarrhea
-Renal tubular acidosis (RTA 1, 2, 4)
-glue sniffing
-hyperchloremia
What are the causes of metabolic acidosis with an increased anion gap?
Methanol
Uremia
Diabetic ketoacidosis
Paraldehyde/phenformin
Iron tablets/isoniazid
Lactic acidosis
Ethylene glycol
Salicylates

AND CHRONIC RENAL FAILURE
What is serum anion gap?
SAG = Na - (Cl + HCO3-)
What are the causes of Respiratory alkalosis?
Hyperventilation
-high altitude

Early aspirin ingestion
What are the causes of metabolic alkalosis?
Diretic use
Antacids
Vommiting
Hyperaldosteronism
What is type 1 Renal tubular Acidosis?
hypokalemic renal tubular acidosis where there is a failure to excrete titratable acid/NH4 which results in systemic acidosis
What is type 2 Renal tubular acidosis?
What does it often occur wtih?
1.There is a renal loss of HC03- due to insufficient reabsorption
2. Fanconi sydrome: failure to reabsorb amino acids, uric acid, phosphate and other organic anions
What is type 4 renal tubular acidosis?
1.Most common form is hyperkalemic aldosterone deficiency RTA 4.
2. failure to excrete NH4
3. hyperkalemia causes decreased production of NH3
What is the nephrotic conditions characterized by?
1. inc. basement membrane permeability
What are the clinical manifestations of the nephrotic syndromes?
1. Massive Proteinuria (4g/day) not accompanied by increased red/white cells
2. Hypoalbunemia (3g/100mL)
3. Generalized edema from decreased oncotic pressure
4. Hyperlipidemia/Cholesterolemia: Caused by increased hepatic lipoprotein synthesis
When is minimal change disease most common?
What are the characteristics?
Under light microscopy?
Under electron Microscopy?
What does it respond to?
1. In children
2. Lipid-laden renal cortices (intracytoplasmic in tubular cells esp PCT)
3. LM is normal
4. EM loss/fusing of foot plate processes
5. responds well to adrenal steroid therapy
What are the characteristics of focal segmental glomerulosclerosis?
1. sclerosis within capillary tufts of deep juxtamedullary glomeruli with focal/segmental distribution
2. similar to minimal change disease
What is the major primary cause of nephrotic syndrome?
When is the highest incidence?
When should the diagnosis be suspected?
1. Membranous Glomerulonephritis?
2. teenagers/young adults?
3. if nephritic syndrome is accompanied by azotemia
What are the morphological characteristics of Membranous glomerulonephritits?
What is its cause?
1. greatly thickened capillary walls (LM)
2. EM 5-10 fold increase of BM
3. electron dense immune complexes in intramemranous and epimembranous locations within/on the BM
4. The cause of membranous glomerulonephritis is of immune complex origin
What disease have spike and dome appearence resulting form the extension of basement membrane bentween and around immune deposits?
1. membranous glomerulonephritis disease
What is the progression of Membranous glomerulonephritis disease?
It is seen in 10% of what patients?
1. slowly progressive with little response to steroid therapy
2. SLE
What is membranous glomerulonephritis associated with?
1. hep B
2. Syphilis
3. Malaria
4. malignancy
5. gold salts
6. penicillamine
7. renal vein thrombosis
Diabetic Nephropathy is manifested by which syndrome?
What does EM demonstrate?
1. nephrotic syndrome
2. Stricking increase in thickness of glomerular BM, thickening of vascular BM
In diabetic nephropathy an increase in the mesangial matrix results in which two characterisitc morphologic patterns?
1. diffuse glomerulosclerosis
2. nodular glomerulosclerosis (Kimmelstiel Wilson Nodules
What does renal amyloidosis cause?
Where are the amyloid deposits?
1. nephrotic syndrome
2. subendothelial/mesangial
What stains are used to identify amyloidosis?
1. Congo red
2. crystal violet
3. thiflavin T
4. bifringence under polarized light
5. criss cross fibrillary patern
What is renal amyloidosis associated with?
1. Chronic inflammatory diseases or plasma cell disorders
(RA/multiple myeloma)
What does SLE cause?
Lupus nephropahy a type of nephrotic syndrome.
What is Type I Lupus NP?
What is Type II Lupus NP
1. No observable renal involvment
2. Mesangial form (focal/segmental increase in mesangial matrix resulting in slight proteinuria/hematuria)
What is Type III Lupus NP?
1. Focal Proliferative form involving less than half of the glomeruli but can cause extensive damage to individual glomeruli
What is Type IV Lupus NP?
1. Diffuse proliferative form (most severe)
2. almost all glomeruli involved
3. marked inflammation with small focal thromboses/mesangial proliferation
What is the wire loop deformity?
1. Characteristic change seen in Type IV lupus nephropathy (immune complex deposition and gross thickening of the glomerular BM and endolthelial cell proliferation)
What is type V lupus NP?
1. Membranous form indistinguishable from primary membranous glomerulonephritis
What is nephritic syndrome characterized by?
inflammatory rupture of the glomerular capillaries and bleeding into the capillary space (proteinuria and edema may be present but usually are mild)
What are the clinical findings of nephritic syndrome?
1. Oliguria
2. azotemia
3. hypertension
4. Hematuria (red cell casts)
What are the forms of nephrotic syndrome?
1. minimal change disease
2. focal segmental glomeruloscelerosis
3. membranous glomerulonephritis
4. diabetic nephropathy
5. renal amyloidosis
6. Lupus Nephropathy
What disease is characterised by lumpy/bumpy immunoflourescence, electron dense humps and enlarged hypercellular, swollen bloodless glomeruli followed by an infection (impetigo, tonsillitis, infected insect bites)?
1. post streptococal glomerulonephritis (immune complex disease)
2. most recover, some develope rapidly progressive crescentic glomerulonephritis (50% of RPGN Type I)
What is the definition of rapidly progressive crescentic glomerulonephritis?
nephritic syndrome that progresses rapidly to renal failure in weeks or months
What is the defining characteristic of rapidly progressive glomerulonephritis?
What do they result from?
What do 10% of patients present like?
1. crescents between the bowman capsule and the glomerular tuft
2. Fibrin depostion and proliferation of parietal epithelial cells
3. Goodpasteur syndrome with antiglomerular basement membrane antibodies (nonstrep) (Type II)
If there are no immune complexes in a patient presenting with RPGN what is the diagnosis? What else would one find?
1. pauci immune crescentic glomerulonephritis
2. p-ANCA's (Type III)
What are the three types of RPGN caused by?
1. Type 1 post strep infection
2. antiglomerular basement membrane antibodies
3. p-ANCA (pauci immune)
What is goodpasteur's syndrome caused by?
1. antiglomerular basement membrane antibodies directed at glomerular and pulmonary alveolar basement membranes
What does IgG flourescence in goodpasteurs syndrome demonstrate?
1. linear flourescence
What are the clinical manifestations of Goodpasture Syndrome?
1. Nephritic syndrome
2. pneumonitis with hemoptysis
3. men in mid 20
4. RPGN crescentic morphology with linear immunoflourencese.
What disease causes inflammatory focal and segmental changes that are inflammatory and prolifferative?
What is it associated with?
1. Focal glomerulonephritis
2. immune complex disease (SLE, bacterial endocarditis, polyarteritis nodosa, Goodpastures syndrome, Wegener granulomatosis, IgA nephropathy)
What is Alport Syndrome?
What is it associated with?
What is the progression of the disease?
1. hereditary nephritis
2. nerve deafness and lens dislocation/cateracts
3. nephritic syndrome progressing to end stage renal failure by 30
What disease is characterised BM thickening and splitting of the lamina densa?
What gene is it associated with?
1. Alports Syndrome
2. mutation in gene for alpha 5 type IV collagen
What is IgA nephropathy also known as?
Where is IgA deposited?
1. Berger Disease
2. In the mesangium
What is IgA nephropathy characterised by?
1. benign recurrent hematuria in children following infection lasting 1-2 days
IgA nephropathy can be assocated with which childhood vascular disease?
1. Henoch-Schonlein disease
What are the clinical and histological characteristics of membranoproliferative glomerulonephritis?
1. slow progression to chronic renal disease
2. thickening of BM (double tram track appearance) and cellular proliferation
What two forms does membranoproliferative glomerulonephritis come in?
1. Type 1 immune complex of unknown origin with striking tram track appearance
2. Type II Dense deposit disease C3 adjacent to dense deposits (may be IgG cause) less obvious tram track.
What are the clinical manifestations of urinary tract obstruction?
1. renal colic (excrutiating pain caused by distension of ureter)
2. hydronephrosis
3. recurrent infection proximal to site of obstruction
What are the general considerations in UTI's?
1. incidence inc in women/more if pregmant
2. can be cause by hematogenous dissemination of bacteria to kidney/or external entry
3. usualy Escherechia coli
What are the predisposing factors of UTI's?
1. Urinary obstruction
2. surgery
3. catherters
4. gynecological abnormalities
What are the clinical manifestations of a UTI?
1. urinary frequency
2. dysuria
3. pyuria: large number of neutrophils in the urine
4. hematuria
5. Bacteriuria
What are the Findings in acute pyelonephritis?
1. fever
2. leukocytosis
3. flank tenderness
4. urinary white cells
5. urinary white cell casts (pathognomic)
Greatly increased in pregnancy
What is pathognomonic for acute pyelonephritis?
1. urinary white cell casts
What are the characteristics of cystitis?
1. pyuria
2. hematuria
3. urinary white cell casts are not found (because no kidney infection)
What are the most common causes of drug induced interstitial nephritis?
1. penicillin derivatives (e.g. methicillin)
2. NSAIDs
3. Diuretics
What is characteristic of of drug induced interstitial nephritis?
1. acture interstitial renal inflammation that resoloves on cessation of drug.
What is renal papillary necrosis associated with?
Abuse of what drug can cause it?
1. diabetes mellitus (with pyelonephritis/vascular disease)
2. Can be catastrophic consequence of acute pyelonephritis
3. Phenacetin in assoc with asprin
What is chronic analgesis nephritis?
1. a chronic inflammatory change characterized by loss and atrophy of tubules and interstitial fibrosis and inflammation
What is acute tubular necrosis?
1. a reversable condition (necrotic cells are replaced by new cells in 2 weeks)
2. Must be on dialysis
What is the major complication of acute tubular necrosis?
1. cardiac stand still due to hyperkalemia
2. usually during the acute oliguric phase
What must oliguria from acute tubular necrosis be distinguished from?
1. loss of volume
2. SIADH
3. dehydration
What causes acute tubular necrosis?
1. renal ischemia
What are the causes of renal ischemia?
1. prolonged shock/hypotension caused by
1. gram-negative sepsis
2. trauma
3. hemorrhage
What does a crush injury have to do with acute tubular necrosis?
a crush injury releases myoglobin and causes myoglobinuria
What toxins can cause acute tubular necrosis?
1. mercuric chloride
2. gentamicin
3. ethylene glycol (anti-freeze, also causes oxalosis)
What is fanconi syndrome?
1. generalized dysfunction of the proximal renal tubules (aquired or heriditary)
2. impairment of glucose, amino acids, phosphate and bicarbonate reabsorption
What are the clinical manifestations of fanconi syndrome?
1. glycosuria
2. hyperphophaturia
3. hypophosmatemia
4. aminoaciduria
5. systemic acidosis (no bicarbonate)
What is Hartnup disease?
1. impaired tubular reabsorption of tryptophan is genetically determined
2. leads to pellegra like symptoms
What findings are essential to the diagnosis of chronic pyelonephritis?
1. coarse, asymmetric corticomedullary scarring and deformity of the renal pelvis and calyces
What are the characteristics of chronic pyelonephritis?
1. interstitial inflammatory infiltrate followed by interstitial fibrosis
2. tubular atrophy
3. atrophic tubules contain eosinophillic proteinaceous casts which results in "thyroidization of the kidney"
What is the cause of of chronic pyelonephritis?
1. chronic urinary tract obstruction with repeated bouts of acute inflammation
What are the consequences of chronic pyelonephritis?
1. renal hypertension
2. end stage renal disease
What is diffuse cortical necrosis?
1 acute generalized ischemic infarction of the corticies with spared medulla
What is diffuse cortical necrosis associated with?
what is the cause?
1. associated with obstetric catastrphies (abruptio placentae/eclampsia) and septic shock
2. cause is end organ vaso spasm + DIC
What is the cause of nephrocalcinosis (deposition of calcium in the renal paranchyma?
1. hypercalcemia (hyperparathryroidism/milk-alkali syndrome
2. hyperphosphatemia (as a result of renal failure
3. can be the cause and result of renal failure
Calcium stones account for what percentage of urinary stones?
What do they consist of?
80-85 percent
calcium oxalate and/or calcium phosphate
What causes hypercalciuria?
1. increase intestinal absorption
2. increased renal excretion
3. Hypercalcemia
what causes hypercalcemia?
1. hyperparathyroidism (also causes nephrocalcinosis
2. malignancy due to osteolytic metastasis (PTH secreting tumor like squamous cell carcinoma of lung)
3. sarcoidosis
4. vitamin D intoxication
5. milk alkali syndrome
What is the second most common renal stone?
What is their cause?
1. ammonium magnesium phosphate stones (which are radiolucent)
2. formed in alkaline urine by Urase positive producing bacteria proteus vulgaris/staphylococcus
3. can lead to large staghorn calculi
what are uric acid stones associated with?
1. hyperurecimia in half of patients
2. can be secondary to gout or increased cell turnover in leukemias or myeloproliferative syndromes
When does Adult polycystic disease of the kidney manifest?
What causes it?
1. between ages 15-30
2. autosomal dominant
What are the characteristics of adult polycystic disease of the kidney?
What is APDK associated with?
1, partial replacement of renal parenchyma by cysts in both kidneys
2. enlarged kidneys
3 Berry aneurysms/cystic disease of the liver and other organisms
What are the clinical characteristics of APDK?
1. secondary polycythemia
2. hypertension
3. hematuria
4. palpable renal masses
5. progression to renal failure
What is infantile polycystic KD?
1. autosomal recessive
2. multiple cysts which are closed and not in continuity with the collecting system
3. death shortly after birth
What is Uremic medullary cystic disease?
serious uncommon cystic disease that affects older children
cysts in medulla that may result in renal failure
What is medullary sponge kidney?
small medullary cysts and impared tubular function w/o renal failure
What is aquired cystic disease?
1. multiple cysts, glomerular and tubular atrophy and scarring
2. increased incidence of renal cell carcinoma
3. long term dialysis
What is always associated with renal failure?
What occurs in the advanced stages?
1. azotemia (increased nitrogen containing compunds)
2. Uremia (biochemical and clinical syndrome of symptomatic renal disease)
What are the clinical characteristics of Uremia?
1. azotemia
2. acidosis (accum. of sulfates, phosphates and organic acids)
3. hyperkalemia
4. abnormal control of fluid volume (early inability to concentrate, later inability to dilate urine)
5. Na/water retention can resultin congestive heart failure
6. hypocalcemia (failure to synthesize calcitriol; leads to renal osteodystrophy)
7. anemia
8. renal hypertension (inc. renin)
What are other systemic charateristics of uremia?
1. anorexia, nausea, vomitting
2. neurologic disorder
3. bleeding
4. accumulation of skin urochrome
5. finrinous pericarditis
What is the pre-renal cause of pre-renal azotemia?
1. decreased renal blood flow caused by
a. blood loss
b. decreased cardiac output
c. systemic hypovolemia
d. vasodilation (gram negative sepsis)
What is charateristic of pre-renal azotemia?
1. increased reabosrption of Na/water resulting in oliguria/concentrated urine
What should be meassured in pre-renal azotemia?
1. urinary Na is important in the delineation of oliguria shock
When the Na is low what is the cause of pre-renal azotemia?
1. decreased renal blood flow (maximal Na reabsorption)
When oliguria is accompanied by a normal or increased urinary sodium what is the cause?
1. acute tubular necrosis in which Na reabsorption is greatly impaired
What is the BUN: creatinine ratio in Oliguric shock?
greater than 15 due to decreased GFR and increased tubular reabsorption of urea
What is a BUN:creatinine ratio over 30 indicitive of?
1. GI bleeding
2. blood meal is digested increases urea (from protein metabolism)
What is the cause of postrenal azotemia?
mechanical blockage of urinary flow
What are the benign tumours of the kidney?
1. Adenoma (small/asymptomatic)
2. Angiomyolipoma (hamartoma of fat/smooth muscle/ and blood vessels)
What is a kidney adenoma derived from?
What is angiomyolipoma often associated with?
1. renal tubules
2. tuberous sclerosis
What are the malignant tumours of the kidney?
1. renal cell carcinoma
2. Wilms Tumor
What is the most common renal malignancy?
Who is it more common in?
1. renal cell carcinoma
2. Men aged 50-70, smokers
When gene deletions is renal cell carcinoma associated with?
1. ch. 3 (also associated with Hippel-Lindau disease)
Where does renal cell carcinoma originate?
1. renal tubules often in the upper pole
Where does the tumor often invade?
What is the result?
1. Vena Cava/renal veins
2. early hematogenous dissemination
What are the histologic characteristics of renal cell carcinoma?
1. polygonal clear cells with vestigial tubule formation
What are the presenting features of renal cell carcinoma?
1. flank pain
2. palpable mass
3. hematuria (most fz)
What are the clinical features of renal cell carcinoma?
1. fever
2. secondary polycythemia (from increased erythropoetin production)
3. extopic production of ACTH, prolactin, gonadotrophins and renin
4. para neoplastic PTH
What is the most common renal malignancy of early childhood?
When is it Common?
1. Wilms Tumor
2. age 2-4
Where does Wilm's tumor originate from?
1. primitive meanephric tissue
What are the histological characteristics of a Wilms Tumor?
varied with immature stroma, primitive tubules and glomeruli and mesenchymal elements and fibrous connective tissue
What is the presenting feature of a Wilms tumor?
1. huge palpable flank mass
What are the gene deletions associated with Wilms Tumor?
1. WT-1, WT-2 on chromosome 11
2. Genomic imprinting: abnormal alleles are always of maternal origin
What abnormalities are associated with a WT-1 deletion?
Wilms tumor
Aniridia
Genitourinary malformations
Retardation
What abnormalities are associated with a WT-2 deletion?
1. Beck-with-Weidmann syndrome
2. hemihypertrophy
macroglossia
organomegaly
neonatal hypoglycemia
embryonal tumors
What is Denys-Drash Syndome?
1. WT-1 abnormality
with intersexual disorders, nephropathy and wilms tumor
What is the most common tumor of the collecting system?
1. transitional cell carcinoma (calyces to bladder)
Abuse of what drug is associated with transitional carcinoma in the renal pelvis?
1. phenacetin
What is the most common presenting feature of transitional cell carcinoma?
1. hematuria
What toxic exposures are associated with transitional cell carcinoma?
1. industrial expsure to benzidine/naphthylamine
2. cigarette smoking
3. long term treatment with cyclophosphamide
What is the least common of UT cancers?
What is it associated with?
1. squamous cell carcinoma
2. chronic bacterial infection or infection with Schistomsoma haematobium
3. renal calculi