Lectures Flashcards
(143 cards)
1
Q
Describe the structure of the kidney.
A
The capsule surrounds the cortex, which surrounds the medulla. The tips of the medulla are called papilla, which point inwards to each calyx. The calyces all collect into the renal pelvis, which exits into the ureter. Near the renal pelvis is where the renal vein and artery pass through.
2
Q
Describe the nephron structure.
A
Blood flows through the glomerulus, which filters into the proximal convoluted tubule, which passes into the medulla via the pars recta, before becoming the thin descending limb, thin ascending limb, and thick ascending limb (all part of the Loop of Henle). The thick ascending limb goes back into the cortex, passes next to the glomerulus with Macula Densa cells lining it, before becoming the distal convoluted tubule which drains into the cortical collecting duct and medullary collecting duct.
3
Q
Describe the different types of nephrons.
Describe the two capillary networks.
A
In humans, the short-loop nephrons with short loops of Henle make up 7/8 of the nephrons, and the long-loop nephrons with long loops of Henle make up 1/8 of our nephrons.
The afferent arteriole becomes the Glomerular capillary network, but because this is high pressure filtration environment, the efferent arteriole reduces pressure before entering the peritubular capillary network (where pressure is low enough for reabsorption).
4
Q
Describe the filtration of urine.
A
Filtration occurs at the glomerulus (180L per day). The structural barrier is via a three layer membrane (endothelium / basement membrane / podocyte cells with filtration slits. Anything under 5,000 MW can pass through, above 70,000 MW cannot.
The electrical barrier means that the Podocyte layer and basement membrane have negatively charged glycoproteins, repel negatively charged plasma proteins, thus less charge lets proteins pass and causes proteinuria.
5
Q
Describe the reabsorption of water.
A
67% of it is reabsorbed in the proximal tubule, and 8-17% is reabsorbed in the distal tubule and collecting duct (where fine tuning occurs).
Much of it goes around the cells through a special type of tight junction, through the lateral intercellular space, and follows sodium into the peritubular capillaries. A little bit of water does leak back through the tight junctions, however. If the spaces swell, the passive back leak will increase.
6
Q
Describe the dynamics of filtration.
A
GFR means Glomerular filtration rate, and may be 125 mL/min. The filtration fraction (FF) may be 20%, or 20% of the plasma that passes through the glomerulus gets filtered. But enough is reabsorbed that only 1% overall stays in the tubule. FF therefore refers to the percentage of plasma, not blood, that is filtered. Hydrostatic pressure resists entry of fluid, and oncotic pressure pulls fluid in. The major force by far is the Glomerular capillary hydrostatic pressure. This is a disequilibrium capillary thus the pressures never balance, so there is always filtration.
7
Q
How do you calculate the direction of fluid flow in filtration?
A
Add up oncotic pressures and hydrostatic pressures in favor of filtration, and subtract from them the hydrostatic and oncotic pressures opposing filtration, and see if the sum favors or disfavors filtration.
8
Q
Describe factors that affect GFR and renal blood flow.
A
Increasing renal blood flow will increase GFR.
Relaxing the afferent arteriole will increases GFR and RBF. Constricting it will decrease GFR and RBF. Relaxing the efferent arteriole will increase RBF but decrease GFR. Constricting it will decrease RBF but increase GFR.
Higher Bowman’s capsule hydrostatic pressure will decrease GFR, as will higher plasma oncotic pressure. Higher membrane permeability or surface area will increase GFR.
9
Q
Describe the autoregulation of GFR.
A
GFR and RBF remain mostly stable in a range of blood pressures. Thus arteriole tone can keep a steady rate of filtration (myogenic theory). Or the tubule triggers regulation by getting the macula densa to detect a higher sodium delivery rate and control the afferent arteriole via a paracrine effect (tubuloglomerular / Macula Densa feedback theory).
Extrinsic factors like sympathetic nerves / angiotensin II / vasopressin can override and shut down this autoregulatory mechanism.
10
Q
Briefly describe reabsorption.
A
Reabsorption occurs at the tubules into the peritubular capillaries (99% of the filtered volume).
11
Q
Describe renal clearance and how it is measured.
A
Clearance is the volume of plasma that was cleared of this substance per unit time. This tells you how efficiently the kidney cleans up the plasma. You can use clearance to indirectly measure GFR is your substance is freely filtered by the glomerulus, does not get reabsorbed or secreted (which would bias the result), and does not get metabolically destroyed or produced. Inulin (a polysaccharide) can do this. Excreted inulin therefore equals the filtered inulin.
12
Q
Describe a tricky concept of inulin.
Describe using inulin clearance as a benchmark.
Explain why we use the terms ‘net’ secretion and absorption.
A
The clearance of inulin is constant regardless of plasma concentration because the GFR is constant (and because clearance refers to a volume not a concentration).
If a substance has higher clearance than inulin, there is net secretion. If a substance has a lower clearance than inulin, there is net absorption.
The net effect is measured, but even a substance that has net secretion may be absorbed in some places and secreted in others.
13
Q
Describe what creatinine can tell you.
A
Creatinine is filtered but a little bit is also secreted as well, thus it overestimates the GFR by about 15-20%. Ccr is 15-20% higher than Cin and GFR. Although creatinine clearance is less accurate than inulin clearance, it is most commonly used because it is an endogenous substance and doesn’t have to be infused.
Furthermore, elevated plasma creatinine tells you that the kidneys are suffering from low GFR (but it only rises after 50% of renal function has been lost).
14
Q
Explain how you measure renal plasma flow.
A
Para-aminohippurate (PAH) and Diodrast are freely filtered and also highly secreted from the peritubular capillaries, thus almost all of the renal plasma loses its PAH / Diodrast. So the PAH / Diodrast in the urine tells you the total amount of plasma that flowed through the nephron.
15
Q
Describe renal micropuncture.
A
Needles can measure or inject materials into different parts of the tubule. You can compare the concentration of these substances in the tubule fluid relative to plasma concentration to see what happened (TP/F ratio). This only tells you if something has been reabsorbed or secreted faster than water (TF/P ratio starts at 1 and becomes non unity). If the TF/P ratio stays at one, it may still have been reabsorbed or secreted, it’s just doing so at the same rate as water.
16
Q
Name two things with a TF/P ratio that starts at 1 but drops to 0.
Name something with a TF/P ratio that starts at 1 but rises to 3?
What has the highest TF/P?
A
Glucose (because all of it leaves the tubule fluid) and amino acids. Both of these are reabsorbed much faster than water.
Inulin (because water is reabsorbed without inulin, this concentrating inulin in the tubule fluid). It is concentrated three fold (1 to 3), thus 2/3 of the water was reabsorbed in the proximal tubule.
PAH (because it gets concentrated when all of the water gets reabsorbed, and then additional PAH is secreted, thus concentrating it even more).
17
Q
Describe sodium reabsorption.
A
90% of sodium is reabsorbed in the proximal tubule (thus it is the major driving force for water reabsorption here). The sodium / proton antiporter (which makes urine acidic) and sodium / glucose / amino acid symporters (which explain why glucose and amino acids are so rapidly absorbed) pull sodium from the lumen.
The sodium potassium ATPase then moves sodium into the peritubular capillary.
18
Q
Describe the transport of potassium.
Describe the transport of urea.
A
Like water, 67% is reabsorbed in the proximal tubule. This is because potassium follows water through passive paracellular movement, thus 67% of water pulls 67% of potassium along with it. More is reabsorbed in the thick ascending limb and the early distal tubule, but some potassium is eventually secreted in the late distal tubule to re-enter the urine.
50% is reabsorbed passively in the proximal tubule, secreted into the thin ascending limb.
19
Q
Describe glucose and amino acid transport.
A
99% of glucose and amino acids are reabsorbed in the proximal convoluted tubule through sodium symporters, like the SGLT2 (sodium glucose luminal transporter) in the early proximal convoluted tubule, and the SGLT1 in the late proximal convoluted tubule.
20
Q
Describe the function of the distal nephron.
A
The distal nephron is more of the fine tuning portion. In the early distal tubule, sodium and chloride are reabsorbed through a cotransporter, where water cannot follow them (not water permeable). A sodium potassium pump, with a chloride channel, then move sodium and chloride into the peritubular capillary.
In the late distal tubule and collecting duct, principal cells reabsorb sodium and secrete potassium (due to aldosterone). Intercalated cells secrete protons and reabsorb bicarbonate to acidity urine (and may even reabsorb potassium).
21
Q
Describe the glucose reabsorption curve.
A
At low plasma glucose concentrations, the glucose reabsorption scales linearly as a straight line (all glucose is reabsorbed) and the glucose excretion curve remains at zero (none makes it into the urine). But as plasma glucose increases, the glucose reabsorption maxes out to a flat line (transporters are saturated) and the glucose excretion begins to rise up from zero (extra glucose begins making it into the urine).
22
Q
Describe osmotic diuresis.
Describe the reabsorption rate.
Calculate excretion.
A
An excess of solute which is normally reabsorbed (glucose) pulls water out with it, or a solute that cannot be reabsorbed (mannitol) pulls water out with it, or reabsorption of the solutes are inhibited (by a diuretic drug).
Take what is filtered and subtract from it what made it out (excretion).
Excretion = filtration plus secretion minus reabsorption.
23
Q
Describe the PAH secretion curve.
Describe how units may trick you.
A
PAH secretion scales linearly with the plasma concentration, but eventually the secretion mechanism maxes out, thus the secretion curve flattens our. However, the amount of PAH that is excreted will still continue to increase because more is still being filtered out (even if secretion has already reached a maximum).
Clearance is a volume per time (L / minute) whereas secretion / excretion / reabsorption / filtration are all an amount per time (so that they can all be in the same equation as each other).
24
Q
Describe the body fluid compartment breakdown.
A
The body has 60% of their weight composed of water.
2/3 is Intracellular fluid, 1/3 is extracellular fluid. Of the extracellular fluid, 3/4 is interstitial and only 1/4 is plasma.
Transcellular fluid includes CSF / synovial fluid / intraocular fluid / pericardial fluid, which is outside of cells but separated from the plasma by more than just the endothelium.
25
Describe the types of fluid loss.
Insensible water loss (water leaks through skin and lungs) for about 900ml per day.
Sweat means water lost through glandular secretion, it about 100mL per day, but exercise can dramatically increase this. Note that sweat is hypotonic relative to plasma, thus you lose more water than solutes.
Feces loses about 100mL per day, whereas urine loses about 1,500 mL per day. Urine is the only one that can be adjusted physiologically, thus it is the most important source of water loss.
26
Describe the function of the Loop of Henle.
It dives from the isotonic cortical interstitial fluid to the hypertonic medullary interstitial fluid. Water is sucked out of the thin descending loop of Henle, which is water permeable, but slightly permeable to urea, and completely blocks sodium. So the tubular fluid osmolarity increases. In the thin ascending limb the opposite is true. Sodium is permeable, urea is moderately permeable, and it blocks water. So sodium gets pulled into the interstitial fluid, and some urea (concentrated in the interstitium) gets pulled from** the interstitial fluid. Then sodium is actively transported out of the thick ascending tubule (diluting section), which decreases osmolarity.
27
Describe the function of the late distal tubule and collecting duct.
ADH makes the late distal tubule and cortical collecting duct water permeable by fusing aquaporin II vesicles with the luminal membrane through a cAMP mechanism, thus water flows through them to the higher osmolarity interstitial fluid and concentrates urine. In the inner medullary collecting duct, ADH will also cause urea to diffuse into the deep interstitium thus diluting urine. This establishes high concentration of urea in the medullary interstitium.
28
# Define free water clearance.
What can tell you that there is no free water clearance? Diluted urine tells you what?
The excess of deficit of pure water that has been added to the urine flow. The equation is:
Free water clearance = urine volume that comes out minus osmolar clearance that entered nephron to begin with. (Thus positive free water clearance adds water to the urine, whereas negative free water clearance reabsorbs water and concentrated urine).
If the urine osmolarity and plasma osmolarity are equivalent, then the free water clearance is zero because no water has been added to dilute the urine. Diluted urine indicates positive free water clearance.
29
Describe the control of ADH secretion.
There is osmotic control and volume control. Osmotic control has osmotic receptors in the hypothalamus trigger more water to be retained if the blood is too concentrated, by releasing ADH. Volume control has high pressure arterial baroreceptors (aorta) and low pressure cardiopulmonary baroreceptors (atrium) release ADH to increase blood pressure.
30
Describe the control of extracellular fluid sodium concentration.
Sodium salts result in 90% of the ECF osmolarity. Thus there are two mechanisms that control sodium concentration. ADH and thirst. ECF sodium concentration is adjusted by changing the amount of the water, not the amount of the sodium. Thus high sodium causes high blood pressure or dilute it out, by triggering ADH. The ADH control of water kicks in before you feel thirsty, at a lower plasma osmolarity threshold. When ADH reaches maximal responsiveness and cannot concentrate urine any more, then you get very thirsty.
31
Describe the sensitivity of ADH release.
Only at high levels, ADH functions as a what? So what is it called?
Describe the role of the sympathetic nervous system in sodium control.
ADH release is not that sensitive, as it requires a 10% decrease in blood volume to trigger ADH. ADH increases much more sharply with hypovolemia or hypotension, and increases much more gradually with hypervolemia or hypertension.
Vasoconstrictor, vasopressin.
If blood pressure is low, renal sympathetic nerves will constrict afferent arterioles to decrease GFR and RBF, stimulate RAAS system, and directly stimulates sodium reabsorption in the proximal tubule (minor effect). All of these increase blood pressure.
32
Describe the RAAS system.
The renin-angiotensin-aldosterone-system has dehydration lower blood volume, which lowers blood pressure, which releases angiotensinogen from the liver and renin from the juxtaglomerular kidney cells. Renin turns angiotensinogen into angiotensin I, which ACE from the lungs turns into angiotensin II, which can directly constrict ***efferent*** arterioles to lower RBF (while paradoxically maintaining GFR for normal kidney function), and also trigger the adrenal cortex to release aldosterone which increases sodium and water reabsorption.
33
Describe renin release triggers.
Describe why ACE inhibitors may make stenosis even worse.
Renin can be released when the sympathetic nerves directly stimulate the kidneys, when the afferent arteriole has less stretch due to low pressure, and lower GFR decreases macula densa sodium load (due to lower blood pressure).
Stenosis decreases blood flow to the kidneys. Angiotensin II constricts the efferent arteriole to maintain GFR, but ACE inhibitors relax the efferent arteriole and can drop the kidney perfusion pressure to dangerously low levels.
34
Describe the effect of aldosterone.
More aldosterone increases sodium reabsorption and secretes potassium (thus preserving sodium).
Less aldosterone causes more sodium to be excreted in the urine, and less potassium to be excreted (thus preserving potassium).
35
Describe the natriuretic peptides.
These have the opposite function of the RAAS system, and cause blood pressure to decrease by triggering more urination. Atrial natriuretic peptide (surprisingly more in the ventricle than the atrium) and brain natriuretic peptide will dilate vessels, decrease renin / ADH / aldosterone, increase the GFR and decrease sodium reabsorption, thus all of this decreases blood pressure.
36
High pressure baroreceptors mainly increase blood pressure by what means?
Low pressure baroreceptors mainly increase blood pressure by what means?
Juxtaglomerular apparatus mainly increases pressure by what means?
Activating the sympathetic nervous system to excite the heart and trigger cardiac muscle.
Increasing ADH (and not the sympathetic nervous system).
Triggering the RAAS system by releasing renin (hence renal control of the RAAS system).
37
# Define acidemia.
Define alkalemia.
Define acidosis.
Define alkalosis.
Acidemia means the plasma pH is less than normal.
Alkalemia means the plasma pH is greater than normal.
Acidosis describes a process where there is a net gain of protons.
Alkalosis describes a process where there is a net loss of protons.
38
Describe the systems that regulate body pH on different time scales.
Describe the effect of pH on ventilation.
Buffer systems immediately regulate pH changes within seconds. The lungs regulate pH over several minutes by modifying CO2 removal. The kidneys regulate pH changes over hours by modifying proton secretion and bicarbonate reabsorption.
Low pH increases ventilation, which reduces the CO2 in the blood, thus raising the pH.
High pH slows down ventilation, which causes Co2 to accumulate in the blood, thus lowering the pH.
39
Loosely describe the renal regulation of pH.
Name the three mechanisms that do this.
The kidneys ***secrete*** protons and ***reabsorb*** and generate new bicarbonate. They must generate additional bicarbonate because the amount being reabsorbed is insufficient to keep our blood buffered.
Proximal tubular mechanism, the collecting duct mechanism, and the loop of Henle mechanism.
40
Describe the proximal convoluted tubule mechanism for bicarbonate.
Proximal tubular mechanism = filtrated bicarbonate binds with secreted protons (sodium proton exchanger) to make carbonic acid, which carbonic anhydrase turns into water and CO2, which easily diffuses into the cell to reform bicarbonate. 80-85% of the bicarbonate reabsorption happens in the PcT, and it is reabsorbed faster than water thus it has a TF/P ratio is less than one.
41
Describe the collecting duct mechanism for bicarbonate.
Describe tubular secretion of bicarbonate.
Collecting duct mechanism = the ***alpha*** intercalated cells actively pump protons into the tubule fluid, which reacts with the bicarbonate to for carbonic acid that degrades on its own (without carbonic anhydrase) to form water and Co2.
***Beta*** intercalated cells turn CO2 and water into carbonic acid, which carbonic anhydrase turns into bicarbonate and a proton. They then secrete the bicarbonate ion into the tubule fluid (in exchange for chloride to balance the negative charge), which also pushes protons into the blood.
42
Describe the loop of Henle mechanism for bicarbonate.
The same sodium / proton exchanger as in the proximal tubule secreted protons, but just like in the collecting duct, there is no carbonic anhydrase.
43
Describe the mechanisms that actually create new bicarbonate, beyond just retaining old bicarbonate.
In the proximal tubule, the titratable acid excretion generates carbonic acid, which is split into a proton and bicarbonate. The bicarbonate is secreted into the blood and the proton is secreted into the tubule fluid (hydrogen sodium exchanger), which joins HPO4 to make H2PO4 (called the phosphate buffer system) which buffers tubule fluid before it is excreted.
The same mechanism happens in the collecting duct, but the only difference is that an ATPase actively pumps the proton into the tubule fluid without using a sodium/proton antiporter.
44
What renal mechanism can increase in an acidosis, with what limits?
What mechanism cannot increase in acidosis?
The titratable acid excretion mechanism can increase to add more bicarbonate in the blood, but as it pumps more protons into the tubule fluid, you run out of HPO4 to accept it in the tubule fluid. This mechanism can therefore only increase slightly (2-3 fold).
The bicarbonate reabsorption mechanism cannot increase at all.
45
Describe the ammonium excretion mechanism.
This is the most flexible mechanism for excreting protons. In the proximal tubule, glutamine makes ammonia and bicarbonate. The new bicarbonate enters the blood, whereas the ammonia is secreted as ammonium.
The ammonium reaches the loop of Henle, which gets reabsorbed (with sodium and two chlorides to balance charge), and becomes ammonia that enters the blood to be reused.
In the collecting duct, ammonia or ammonium enters the cell, but ammonia enters the tubule to accept a proton. This is the most important means to increase hydrogen excretion in acidosis, because it can increase 10 fold.
46
Describe the factors that can increase proton secretion.
Lower Intracellular pH and higher Co2 will secrete more protons. aldosterone will also trigger the proton ATPase to secrete more protons.
47
Describe metabolic acidosis.
Metabolic acidosis is not due to CO2 retention and is therefore not due to a respiratory cause. This is anything that tips the scale to a lower pH. If uncompensated, there will be a low pH with normal CO2. But the lungs will increase their ventilation rate to reduce CO2, so if compensated, there will be low pH with low CO2 (the lungs compensated by releasing CO2 / respiratory compensation). Bicarbonate will also decrease due to buffering acidic blood, as well as due to the loss of CO2. Kidneys will retain as much bicarbonate as they can, form more bicarbonate, and create more ammonium to secrete protons.
48
Describe metabolic alkalosis.
Alkalosis that does not result from too much ventilation / Co2 removal. If uncompensated, the pH will be too high but the CO2 will be normal. As the lungs compensate, however, breathing rate will slow and the pH will be too high with high CO2. Bicarbonate will increase as it has fewer protons to buffer, so kidneys will reabsorb less bicarbonate and secrete fewer protons (to acidity blood). Some bicarbonate will therefore be excreted in the urine. Less ammonia will be secreted thus carrying away fewer protons with it.
49
Describe respiratory acidosis.
This is due to CO2 retention resulting from hypoventilation. Increases CO2 has decrease pH. The problem is this acidosis cannot be buffered by bicarbonate, because this CO2 is already being converted into carbonic acid. It cannot buffer itself, thus the major form of buffering is Intracellular. Furthermore, the lungs cannot compensate because they are the problem, so the kidneys must compensate. They secrete more protons, secrete more ammonia, more bicarbonate is filtered out but also more of it is also reabsorbed. So this **does** increase bicarbonate even more, but it doesn’t matter because we lost protons.
50
Describe respiratory alkalosis.
The lungs are breathing too quickly and eliminate too much CO2, raising blood pH. Buffering will mainly be Intracellular because the bicarbonate level is the issue, and the lungs cannot compensate. So the decrease in CO2 leads to decreased bicarbonate filtration, and therefore decreased reabsorption, but bicarbonate secretion increases to get rid of excess bicarbonate from basic blood thus more bicarbonate is excreted in the urine. There is decreased tubular secretion of protons and ammonium to make the blood more acidic.
51
Explain the Davenport diagram.
It describes the arterial pH on the X-axis, and the bicarbonate concentration on the Y axis. The lines curving up and to the right represent the arterial partial pressure of CO2. pH below 7.35 represents acidosis, and pH above 7.45 is alkalosis. The six quadrants are metabolic acidosis / alkalosis, acute (uncompensated) respiratory acidosis / alkalosis, and chronic (uncompensated) respiratory acidosis / alkalosis. ARAcid is left because left means acidosis and bicarbonate hasn’t had time to increase. CRAcid is upper left because bicarbonate had time to increase. ARAlka is right because right is alkalosis and it hasn’t had time to lower bicarbonate. CRAlka is lower right because bicarbonate has decreased. Metabolic acid = lower left because low bicarbonate decreases pH. Metabolic alkal = upper right because high bicarbonate increase pH.
52
Describe the equilibrium point of the salt / water relationship.
What is the endpoint mediator of sodium secretion? What does it do?
What regulates water via a separate system? Describe it.
Describe why it is stored in the posterior pituitary.
There is a single blood pressure at which the intake of salt and water equals the output of salt and water.
Aldosterone, increased aldosterone increases sodium reabsorption, thus increasing sodium in the blood and decreasing urine output, increasing blood pressure and extracellular volume.
ADH (vasopressin), manufactured in the supraoptic nucleus and PVN to be released from the posterior pituitary.
So that it can be released at a moments notice due to increased plasma osmolality.
53
What are two major separate balance issues with the fluid?
Sodium concentration does not equal what?
Describe three volume statuses and their symptoms.
Salt balance and water balance (these are separate things).
Does not equal volume of their plasma (sodium concentration tells you nothing about their blood volume).
Hypovolemia / hypervolemia, these are easy to spot clinically so we look at these first. Hypervolemia causes edema / ascites / JVD / displaced PMI. Hypovolemia causes tachycardia / decreased skin turgor / dry membranes / thirst. Euvolemia (normal) means they have none of these symptoms.
54
Describe the four possible factors of hyponatremia.
Hyponatremia (low blood sodium concentration) could be ADH reabsorbing water, insufficient sodium intake, excessive water intake, or impaired urine diluting capacity.
55
Thus hyponatremia is most often the result of what two things?
With what three exceptions?
If it’s not these exceptions, then what do you know it must be?
Thus hyponatremia is mostly caused by impaired diluting capacity and inappropriate ADH sucking water into the blood.
1) Polydipsia = Patient is releasing plenty of water in their urine but is simply drinking too much extra water.
2) Tea and Toast syndrome = Patient is making urine with plenty of water in it but is simply not eating enough solute.
3) Hypovolemic hyponatremia = Severe blood loss (tons of symptoms) causes low sodium.
Plain old hyponatremia due to impaired diluting capacity with inappropriate ADH.
56
Name some mechanisms that contribute to maximally dilute urine.
Why are these important to keep track of?
High GFR / minimum sodium resorption at the PCT / preserved activity of Na-K-2Cl in thick ascending limb / preserved activity of Na-Cl in DCT / minimum water resorption in cortical collecting duct.
Any one of these could be impaired thus causing hyponatremia (too much water being reabsorbed or too little salt being reabsorbed).
57
Describe SIADH.
Describe what you must exclude.
Syndrome of inappropriate ADH secretion means too much ADH is released thus causing too much water to be pulled back into the blood which causes hyponatremia.
To diagnose SIADH, you must exclude hypothyroidism (which impairs cardiac output thus lower blood volume causes ADH to be released) and adrenal insufficiency (which causes too much water to be filtered out thus ADH is secreted). Once these are excluded, we can consider SIADH.
58
Describe some causes of secondary SIADH.
Describe hyponatremia treatment.
Describe when you would give 3% saline.
CNS tumors / drug effects / pulmonary disease (all of these increase hypothalamic production).
Remove the offending cause (change drugs, give them hypertonic saline, remove an antidiuretic, increase salt intake (which could worsen congestive heart failure), give them urea powder (which doesn’t exacerbate heart failure).
Give saline when there is such severe hyponatremia (sodium less than 120 mEq/L) that neurological issues occur (seizures) or marathon runners acute hyponatremia.
59
Describe the V2 receptor antagonists.
What must you know about normal saline?
Describe correction of serum sodium that is too quick.
Normally ADH binds the V2 receptor causing aquaporins to be inserted. Tolvaptan and Conivaptan are direct V2 receptor blockers that prevent ADH from inserting aquaporins, thus less water is reabsorbed. These are very expensive and are difficult to control.
Only use normal saline for treatment of hypovolemia.
It causes osmotic demyelination syndrome (central pontine myelinolysis) which causes paralysis / locked in syndrome. Thus you must only increase sodium serum concentration at a limited rate.
60
Describe three factors of Hypernatremia.
Describe the mechanisms that normally maximally concentrate the urine.
Impaired ADH activity (water can’t be reabsorbed which concentrates the blood) / impaired ADH release / impaired countercurrent multiplier.
High GFR / high sodium reabsorption at PCT (where water is also reabsorbed with it) / high concentration gradient in LH (which pulls water out of urine) / minimum tubule fluid delivery to thick ascending limb and DCT (because once water gets past this point it cannot be reabsorbed well).
61
Describe how you manage Hypernatremia.
Describe what you would never use normal saline for.
Describe what else will rarely solve euvolemic hyponatremia on its own.
Describe how you would adjust progress.
Give them D5water (5% dextrose with higher osmolality prevents cells from lysing), and do not decrease sodium concentration by more than 0.5 mEq/L per hour (or else it’s too fast), or you could administer vasopressin (ADH) to reabsorb more water and dilute the blood.
Never use normal saline to treat euvolemic hyponatremia because you need something with a higher sodium concentration.
Fluid restriction rarely works on its own (you have to restrict so much fluid that the patient won’t comply).
Titrate the rate of the drip by checking labs every couple of hours and adjusting the rate of sodium administration.
62
Describe why normal 0.9% saline counterintuitively doesn’t treat SIADH hyponatremia.
Their water elimination system doesn’t work (too much ADH) but their sodium elimination system works just fine. Therefore, all of the sodium will be lost to the urine but none of the water, so the saline you just gave them ends up as pure water in their blood which worsens the hyponatremia. You must use 3% saline to give them so much sodium that some is left over in the blood after some is lost to the urine. Additionally, the higher sodium concentration in the urine allows more water to be cleared (as extra water is sucked into the urine).
63
Describe the problem of drinking too much beer, and the treatment caveat.
Too much beer decreases sodium intake thus causing ‘beer drinkers potomania’, a type of euvolemic hyponatremia. This means they have completely normal ability to excrete free water (just like with tea and toast syndrome), thus normal saline will cause tons of extra water to be pulled into the urine, so normal saline or 3% saline will dramatically increase plasma concentration way too quickly (neurological issues or locked in syndrome) as extra water is sucked out. The only way to treat them is to give them more salt.
64
Describe what a patient with hypernatremia should have.
Describe the things that the presence of dilute urine and hypernatremia may indicate.
A hypernatremic patient should have maximally concentrated urine (so much sodium in their blood that the body tries to retain water to dilute it out, thus concentrating the urine).
Dilute urine may be due to diabetes insipidus (unrelated to diabetes) which causes the body to release tons of dilute urine thus concentrating the plasma sodium. It may be central DI (lack of ADH because the pituitary was damaged possibly by basilar skull fracture) or nephrogenic DI (kidneys don’t respond to ADH thus they release too much water and concentrate the plasma).
65
Describe some ways to treat hypernatremia due to DI.
Describe the sequalae of reduction in serum sodium that is too quick.
Give them IV fluids with 5% dextrose to dilute their plasma, give them recombinant ADH (to retain more water thus diluting the plasma).
Correction of hypernatremia that is too quick (dropping plasma sodium too quickly) will NOT cause osmotic demyelination syndrome, but it will cause cerebral edema (as water flows into the more concentrated brain interstitial fluid) when plasma concentration drops.
66
What is normal blood pH? Normal total serum CO2? Normal partial pressure CO2? Describe the first step for an acid base diagnosis.
Then describe the next step.
Then describe the next step. Describe an anion gap.
7.4, 24 (tCO2), 40 (PaCO2), perform a history and physical which should be useful enough to give you a strong suspicion.
Check to see if the tCO2 and HCO3 are within 10% of each other to check for internal consistency. If they are not consistent, recollect the arterial blood gas samples to re-calculate HCO3 with better accuracy.
Calculate the anion gap which is sodium minus chloride and bicarbonate. Note that bicarbonate level is referred to as total serum CO2. An anion gap indicates unmeasured anions (mostly albumin) other than total CO2 and chloride that add up to balance out positive sodium. Most often it is 12, but you must adjust it for albumin level.
67
Describe how you adjust the normal anion gap for albumin level.
Normal albumin is 4.5 g/dL, but if their albumin level is too low (3.5), subtract 2.5 for unit too low, or 12 minus 2.5 thus their normal anion gap is 9.5 (their anion gap is lower because the lower albumin decreases the size of their anion gap).
If their albumin is higher than normal (say 5.5 instead of 4.5) add 2.5 (per the one extra unit of albumin) to get a normal anion gap of 14.5 (their normal anion gap is higher because extra albumin increased it).
This all tells you what their normal anion gap should be, so you would then compare their measured anion gap to this number to see if it is normal or not.
68
Describe what you do after determining if their anion gap is normal or abnormal.
Examine the pH and total serum CO2 (bicarbonate). If both pH and bicarbonate are too high, or if both pH and bicarbonate are too low, we would call it a metabolic alkalosis or acidosis (if both arrows point in the same direction it is metabolic). Respiratory mechanisms compensate this because the lungs still work.
If pH is low and total CO2 is high, or if pH is high and total CO2 is low, we say it is respiratory acidosis or alkalosis (because the Co2 went up to lower pH, or the CO2 went down to raise pH due to lung dysfunction). Renal mechanisms compensate this because the lungs are the cause of the problem.
69
Describe what you do after finding the primary diagnosis (metabolic / respiratory acidosis / alkalosis).
Determine if there is an appropriate physiological response. If the physiological response that we calculate should happen is not actually occurring, then the physiological response is not normal and there is an additional acid base disorder beyond the compensation of the physiological issue. It’s not that the compensation is failing, but rather that there is a whole new acid base disorder. These double combination acid base disorders can happen in any combination (except for respiratory alkalosis and respiratory acidosis which is just normal breathing).
70
Describe the physiological response formula for acid base disorders.
Describe the causes of elevated anion gap acidosis.
Albert-Dell-Winter’s formula = expected PaCO2 = 1.5 x [tCO2] + 8 (and the final answer can be within a range of plus or minus 2).
MUDPILES (methanol, uremia, DKA, paraldehyde, INH / iron, lactate, ethylene glycol / salicylate)
For these causes of elevated anion gap metabolic acidosis, the negatively charged acid itself causes the increased anion gap.
71
Describe the appropriate physiological response for metabolic alkalosis.
Describe the appropriate physiological response for acute respiratory acidosis.
Describe the appropriate physiological response for chronic respiratory acidosis.
For every mEq/L that tCO2 (bicarbonate) increases Above 24, there should be a 0.7 mmHg increase in PaCO2 above 40 (which your lungs increase to try to acidify the blood).
For every 10 mmHg that PaCO2 increases above 40, there should be a 1 mEq/L increase of tCO2 beyond 24 (as the kidneys increase bicarbonate to alkalize the blood).
For every 10 mmHg that PaCO2 increases above 40, there should be a 3 mEq/L increase of tCO2 beyond 24 (as the kidneys increase bicarbonate even more strongly to chronically alkalize the blood).
72
Describe how you differentiate between acute and chronic respiratory acidosis.
Describe the normal physiological responses to respiratory alkalosis.
Look at their history, if they very quickly had symptoms then they had an acute presentation.
For every 10 mmHg that PaCO2 decreases below 40, there should be a 2 mEq/L decrease of tCO2 below 24 (if acute) and a 4 mEq/L decrease of tCO2 below 24 (if chronic). These factors are 2 and 4 (instead of 1 and 3 for correcting respiratory acidosis) because it is easier to decrease bicarbonate production than to increase it).
73
Describe the only time we use a very special equation.
Only use a delta-delta gap for elevated anion gap metabolic acidosis (AGMA), because there may be a third possible acid base disorder (whereas the others could only have two possible disorders). This asks if the decrease in bicarbonate (tCO2) is what we expect for the increase in anion gap, or use the equation delta AG / delta tCO2. If more of the tCO2 (bicarbonate) than expected is used up to buffer the acidity of the increased anion gap (or a larger delta tCO2), then you have additional non-gap metabolic acidosis is present (delta delta gap ratio of under 1 because delta tCO2 denominator is too large). If less of the bicarbonate was used up than you thought (the remaining tCO2 is too large or delta tCO2 is too low), then additional metabolic alkalosis is present (too much bicarbonate left over), thus the delta delta gap ration is over 2 (as the delta tCO2 denominator is too small).
74
Describe potassium distribution in the body.
Describe potassium intake.
Describe how you assess hypokalemia.
It is like the opposite of sodium. Potassium is the dominant intracellular ion whereas sodium is the dominant extracellular ion, driven by the Na/K ATPase.
We can ingest a huge amount of potassium without it getting too concentrated in the blood, whereas IV administration can quickly cause heart attack.
Look where the potassium went (GI secretion losses, vomiting, diarrhea, laxatives, hyper secretion tumor (villous adenoma), urinary losses (too much aldosterone / increased diuretic delivery of sodium to the distal tubule / magnesium can all cause too much potassium loss.
75
Describe a unique constellation of hypokalemia findings and what they indicate.
Why doesn’t cortisol bind to and activate the same mineralocorticoid receptor as aldosterone?
Describe some ways in which cortisol can trigger hypokalemia.
Describe what else may trigger the cortisol receptor and why it’s important.
Hypokalemia and hypertension, when they occur together, indicate aldosterone having an effect by binding the mineralocorticoid receptor, which increases sodium reabsorption and potassium loss in the DCT.
11-beta hydroxylase in the cell degrades cortisol before it can bind the mineralocorticoid receptor.
A deficiency of 11-beta hydoxylase, inhibitors of 11-beta hydroxylase, or hyper cortisolism (Cushing’s syndrome) can let cortisol survive long enough to trigger the receptor).
Natural licorice can trigger this, thus licorice flavored chewing tobacco can cause hypokalemia.
76
Describe renal artery stenosis.
It could be a fibromuscular dysplasia affecting younger females or atherosclerosis blocking the arteries, which may be unilateral (one kidney) or bilateral (both kidneys).
77
Differentiate between unilateral and bilateral renal artery stenosis.
If unilateral, the bad kidney will increase renin (to raise blood pressure) and aldosterone to try to increase blood pressure. The good kidney detects the high blood sodium and dumps it into the urine, which gets exchanged for potassium later on thus causing hypokalemia. Thus both renin and aldosterone is elevated.
Bilateral renal artery stenosis causes flash pulmonary edema (kidneys block blood thus left ventricle fills up and floods lung), acute kidney injury with ACE inhibitors (as blood pressure decreases even lower).
78
Describe Cushing’s syndrome.
An excess of the glucocorticoid cortisol. If this is because the pituitary is creating too much ACTH, we call it Cushing’s disease. If it is due to the adrenal gland making too much cortisol, we just call it Cushing’s syndrome. This extra cortisol can overwhelm 11-beta hydroxylase thus allowing cortisol to trigger the mineralocorticoid receptor for aldosterone, thus creating the same symptoms as hyperaldosteronism (hypertension and hypokalemia). It will also cause muscle wasting / purplish striae / increased fat pads. But renin and aldosterone will be suppressed to try and reduce the blood pressure.
79
Describe the combination of hypokalemia with hypotension.
Describe Bartter’s syndrome.
Describe Gitelman syndrome.
This suggests an adverse medication effect, or GI losses of ***chloride***, or inherited disorder.
There is a loss of the Na-K-2Cl channel in the thick ascending limb of the Loop of Henle, thus potassium cannot be reabsorbed along with sodium and chloride. Diagnosed in childhood, hypokalemia, hypotension, nephrogenic diabetes insipidus (as the ions kept in the urine pull more water out with them), urinary calcium secretion is increased (unlike Gitelman syndrome).
Later in childhood, hypotension, hypokalemia, hypomagnesemia (magnesium lost in urine), but **reduced** calcium excretion unlike Bartter’s syndrome.
80
Describe gastric losses during hypokalemia with hypotension.
Chloride (not potassium) is lost in the GI tract, due to HCl secretion, thus hypochloremia in the blood decreases chloride in the urine, which means less can accompany potassium as it is reabsorbed, reducing potassium reabsorption in the Na-K-2Cl channels in the thick ascending limb.
81
Describe transmembrane cellular shifts of potassium.
Describe hypokalemia treatment.
Describe the role of magnesium.
Blood potassium suddenly decreases as cells sequester potassium, which can cause hypokalemic periodic paralysis (triggered by salty food), causing weaker muscles or cardia arrest (severe hypokalemia).
Oral replacement of potassium is preferred because it is safer, whereas intravenous KCl bypasses the protection of the GI tract and can easily stop your heart.
If you see hypocalcemia and hypokalemia, assume it is due to the absence of magnesium until proven otherwise (because magnesium is needed for parathyroid hormone which increases calcium and for potassium reabsorption).
82
Describe hyperkalemia.
Describe the treatment for hyperkalemia.
It may result from excessive potassium ingestion which is potentially fatal, or transmembrane shift of potassium into the plasma during rhabdomyolysis or cell lysis, or decreased potassium secretion (kidney failure) or hyporeninemic hypoaldosteronism (too little renin and too little aldosterone) which decreases potassium secretion.
Depends upon three things: IV calcium (to stabilize the heart), insulin (to move potassium inside of cells), bicarbonate (as higher pH moves potassium inside of cells), diuresis (to remove potassium in urine), dialysis (to filter out potassium).
83
Describe blood calcium and it’s measurements.
Describe what can suddenly affect calcium.
Blood calcium is largely bound to albumin (45%), and a lot is free calcium (55%). Total serum calcium includes both parts thus you must adjust for albumin, whereas an ionized calcium level is more accurate measurement of physiologically active calcium.
Correcting metabolic and respiratory acidosis will raise pH thus suddenly dropping ionized calcium levels (less positive charge of plasma), or citrate in transfusions will chelate away ionized calcium in the plasma.
84
Describe PTH.
Parathyroid hormone is the conductor that regulates calcium homeostasis, and PTH increases when there is hypocalcemia. It stimulates osteoclasts (releases calcium and phosphate from bone), stimulates final step of vitamin D production in kidneys (calcitriol synthesis), increases calcium reabsorption, decreases*** PCT phosphate reabsorption, and the small increase in free calcium causes negative feedback inhibition of PTH release from parathyroid glands, and increases both calcium and phosphate absorption in the intestines.
85
Describe vitamin D synthesis and function.
Describe the major cause of vitamin D deficiency.
7-dehydrocholesterol is converted to cholecalciferol by sunlight in the skin (290-320 nm), it then enters the liver and is hydroxylated by 25-hydroxylase to calcidiol (plasma marker for nutritional vitamin D stores), and when activated by PTH, it forms calcitriol via another hydroxylation step (hence tri-ol means another alcohol is present). This increases calcium and phosphate absorption in the GI tract.
Far north or south, the 290-320 nm wavelength does not reach the surface, thus require vitamin D supplementation.
86
Describe vitamin D supplementation.
Describe hyperphosphatemia when PTH is released.
Describe hypercalcemia physiology.
Often given as cholecalciferol or the stereoisomer called ergocalciferol from plants, or eat fish / eggs / mushrooms / milk.
PTH increases both calcium and phosphate. Normally the kidney secretes this phosphate and phopshatonin also gets rid of phosphate. But a problem with phosphatonin (FGF23) or kidney failure causes hyperphosphatemia.
Free calcium binds to calcium sensing receptor to shut off PTH production, so PTH goes down and calcitonin goes up.
87
Aside from PTH, describe some causes of increased bone calcium release.
Aside from PTH, describe some causes of increased reabsorption of calcium.
Describe hypervitaminosis D.
Bone cancer / multiple myeloma can cause this by damaging the bone.
Thiazide diuretics are associated with hyponatremia (remove sodium to cause diuresis) and hypercalcemia (they cause increased calcium reabsorption in the PCT to match the increased sodium reabsorption) thus less calcium is excreted in the urine. Thus thiazides raise plasma calcium and shut down PTH.
Excess vitamin D consumption causes hypercalcemia thus lowering PTH release.
88
Describe FHH.
Describe MEN.
Familial hypocalciuric hypercalcemia is a benign condition that mutates the calcium sensing receptor in the parathyroid gland thus ***normal*** PTH levels will trigger too high of a calcium level. This is where the body falsely tries to maintain an abnormally high calcium level.
Multiple endocrine neoplasia (MEN1 specifically) is a parathyroid / pancreatic / pituitary tumor (MEN1 is the 3 Ps). MEN2a is also associated with parathyroid tumors, thus both MEN1 and MEN2a are associated with hyperparathyroidism.
89
Describe some causes of hypocalcemia and treatment caveats.
Hypoparathyroidism would lower PTH thus preventing calcium is excreted too much causing hypercalciuria. Be careful with oral vitamin D replacement because increased absorption of calcium in GI tract will cause a bunch of calcium to end up in the nephron (as PTH is too low to reabsorb it) thus causing nephrotoxicity.
Hypomagnesemia can also cause loss of PTH release as MG2+ is needed to release PTH from parathyroid gland.
90
Describe a cause of pseudo hypocalcemia.
Describe hypocalcemia treatment.
Describe hypercalcemia treatment.
Hypoalbuminemia may cause pseudohypocalcemia.
Oral calcium is preferred (calcium citrate is absorbed very well by the GI tract), or IV calcium gluconate, which must be carefully watched to avoid heart issues, always check for magnesium levels.
You can treat them with loop diuretics (cause more calcium loss in urine as calcium follows sodium everywhere), bisphosphonates will lock calcium into the bone matrix thus acutely lowering it, dialysis can fix severe hypercalcemia.
91
Describe treatment for hyperphosphatemia and a limitation.
Reduce diet rich in phosphate (soda / peanut butter), baking powder, ingest phosphate binders in the stomach such as calcium acetate to excrete phosphate in the stool, can use dialysis but it does not work very well (because although it can quickly reduce serum phosphate quickly but cellular phosphate will keep replenishing plasma phosphate).
92
Describe the Kidney’s locations and implications.
Describe the main difference between the cortex and medulla.
Describe kidney blood supply.
In the retroperitoneal space in Gerota’s fascia. The left is higher because the liver pushes the right one down, thus we biopsy the left to avoid liver damage.
The cortex contains glomeruli and the medulla does not.
25% of CO goes to kidneys, from a renal artery branching off of the abdominal aorta, which divides into segmental renal arteries -> interlobar arteries -> actuate arteries (Arch over the boundary between cortex and medulla) -> interlobular arteries -> afferent arterioles -> glomerulus -> efferent arterioles -> peritubular capillaries.
93
Describe why kidneys are susceptible to ischemia.
Describe the four basic kidney histologic components.
Describe the glomerulus structure.
Arteries supplying the kidneys are ‘end’ arteries, thus there are no anastomoses, and blocking any artery kills the whole section of kidney tissue distal to it.
Glomerulus / renal tubules and ducts / interstitium / blood vessels.
The vascular pole contains blood vessels, the urinary pole contains the proximal tubule, glomerular capillaries contained within Bowman’s capsule that contains empty urinary space, supported by mesangial cells (with smooth muscle activity) supported in the matrix, which supports the glomerulus. It also has attenuated (flat) and fenestrated (holes of 70-100nm in size) endothelial cells, and parietal epithelial cells surround Bowman’s space.
94
Describe the glomerular basement membrane.
Describe Allport syndrome.
Describe nephrin.
Acellular, type IV collagen with laminin, negatively charged heparan sulfate / fibronectin, average thickness is 300nm.
Thin basemement membrane disease is a defect of collagen type IV, so more permeable to RBCs.
Nephrin is a protein that bridges the filtration slit and prevents glomerular permeability.
95
Describe the PCT histologically.
Describe the loop of Henle histologically.
Describe the DCT histologically.
Describe collecting duct histologically.
PCT had cells with eosinophilic cytoplasm (mitochondria to power reabsorption), well developed PAS microvillus brush border (for high reabsorption rate).
LOH thick descending limb looks like PCT, thin descending and ascending limbs look simple squamous without brush border, and thick ascending limb look like DCT.
DCT has larger lumen than PCT (to collect more water) and has macula densa, lack brush border (much less absorption), eosinophilic (mitochondria to power electrolyte movement).
Very well defined lateral cell boundaries (dark outlines).
96
Describe the histology of urinary passages.
Lined by urothelium (transitional epithelium) 4-6 cells thick, large polygonal cells with umbrella cells on top (which can be multinucleated), cobblestone appearance to create blood-urine barrier.
97
Describe urinalysis.
Describe some factors of specimen collection.
Detects urine composition to infer renal function, but it has limited sensitivity and limited specificity (many disorders can cause same urine composition). This urinalysis may not lead to a specific diagnosis. It can be performed as a general screen, or as a **complete** urinalysis of a renal or urinary tract problem is suspected.
Use a chemically clean container with no preservatives. A simple catch specimen has the most contaminants, whereas a clean-catch midstream specimen (collect in the middle of their urination) has fewer contaminants, and a catheterized specimen has the cleanest specimen (but indwelling catheters are often infected).
98
Describe some specimen handling aspects.
Describe the components of a complete urinalysis.
Get it to lab quickly because urine is unstable, and each specimen must be labeled with identifying information and time of collection (to know how fresh it is).
Macroscopic / chemical / and microscopic analysis. Macroscopic is volume / color / odor / specific gravity.
99
Describe aspects of urine specific gravity.
Urine SG is normally between 1.003 and 1.03, tells you how concentrated urine is.
If their SG changes by a small amount across measurements, may indicate renal damage, as there is poor concentrating or diluting ability.
If their SG changes by a lot, indicates excess dehydration, or renal insufficiency, or an abnormal solute present in the urine.
100
Describe some major aspects of chemical urinalysis.
Describe what affects urine pH.
Describe what affects protein in urine.
PH, protein, glucose, ketones, blood, bilirubin, nitrite, etc. Can use the dipstick test (reagent strips) in small labs, whereas large labs use automated analyzers. These results are only semi-quantitative, so it has a numbered scale but not too specific. You must consider their hydration level when interpreting your results.
PH normally around 6, acidic urines caused by meat (amino acids) and acidosis, basic urines associated with vegetarianism and alkalosis and bacterial infections that split urea to create basic products.
Normally very low albumin excretion, proteinuria caused by many conditions, can clearly indicate damage to glomerulus or tubules. Selective proteinuria means albumin is mostly present, whereas non-selective proteinuria means a whole mix of proteins is present.
101
Describe what affects glucose in urine.
Normally very low glucose in urine, but glycosuria indicates high blood glucose level (too much filtration) or tubular dysfunction (cannot reabsorb glucose). You can use dipsticks covered in glucose oxidase to indicate its presence. But this dipstick test will NOT work for lactose or any other sugar.
102
Describe some facts about ketones.
Made when excess fat metabolism or reduced carbohydrate metabolism, builds up pyruvate thus making ketone bodies. These could be 3-hydroxybutyrate / acetoacetic acid / acetone. Could be in urine due to diabetic ketoacidosis, non-diabetic ketonuria, some metabolic diseases, starvation, low carb diets.
Dipstick test is most sensitive to acetoacetic acid and acetone, but not so much for 3-hydroxybutyrate.
103
Describe some terms relating to bloody urine.
Describe some dipstick complications.
Hematuria means red blood cells are in the urine, but a bunch of these things could cause it (kidney stone, infection). This is the most common.
Hemoglobinuria means free hemoglobin is in the urine, due to intravascular hemolysis which exceeds haptoglobin binding capacity thus excess hemoglobin is filtered.
Myoglobinuria means myoglobin is in the urine, due to acute muscle fiber destruction. This is the rarest.
Heme peroxidase dipsticks do not differentiate between blood, hemoglobin and myoglobin, so any of them can give a positive result. Lots of ascorbic acid also causes false negative.
104
Describe bilirubin in the urine.
A hemoglobin breakdown product that is not normally in the urine, because it is bound to albumin and metabolized by liver. Thus billiary tree obstruction backs it up and excretes bilirubin into the urine. Or hepatocellular disease where it doesn’t get secreted in the first place.
105
Describe urobilinogen in the urine.
Urobilinogen should normally be present in urine (in a small amount), which excretes it after it was absorbed from the gut after bacteria formed it from conjugated bilirubin. If it is completely absent, then you could have bile flow obstruction or absence of GI bacteria by antibiotics. If it is too high, it means the liver cannot remove some of the reabsorbed urobilinogen from circulation (liver damage from drugs or toxins).
106
Describe nitrite in the urine.
Urinary tract pathogens reduce nitrate to nitrite (removing oxygen thus reduction). A positive result indicates urinary tract infection by certain bacteria. If so, send urine sample for culture to verify type of organism. However, they may still have infection even if they don’t have nitrite because their pathogen may not produce it.
107
Describe leukocyte esterase in the urine.
This enzyme is released by leukocytes, thus positive result in urine implies WBCs are in the urine (usually due to bacterial infections if the body).
108
Describe a urinary microscopic evaluation.
Describe epithelial cells in urine.
Used if you suspect a renal or urinary tract problem. Use fresh uncontaminated urine and analyze as soon as you can. You may find RBCs, epithelial cells, inflammatory cells, organisms, crystals, contaminants, or casts.
It is normal to see some epithelial cells in urine, which come from the kidney and urinary tract (urothelial / transitional cells with scarce cytoplasm, or squamous cells with tons of cytoplasm). However, tubular epithelial cells are NOT normally seen (this always indicates injury).
109
Describe fat bodies in urine.
Describe neoplastic cells in the urine.
Describe red blood cells in urine.
Fat bodies are renal tubule epithelial cells that have absorbed lipoproteins. These indicate lipiduria, and can be spotted by polarized light.
Neoplastic cells are not usually seen in the urine, but a special technique called cytologic evaluation or even genetic testing can spot neoplastic renal cells.
They may not look red at all, and may be swollen in hypotonic urine or shrunken in hypertonic urine, thus they can be dysmorphic and have many odd shapes. They can come from damage anywhere in the urinary tract.
110
Describe bacteria in urine.
Describe yeast in the urine.
These appear as tiny cocci or rods in the urine, and are usually contaminants from the vagina, overgrowth in the sample, or possibly from a urinary tract infection (with associated leukocytes). You send them to a microbiology lab to identify them.
Often yeast will be Candida albicans, as women have yeast infections. You can tell it is fungal due to microscopic budding that occurs at the border of the yeast (which otherwise look like cocci because they are both round).
111
Describe parasites in the urine.
Describe viruses in the urine.
Describe a urinary cast.
Trichomonas parasites are the most common in the US for urinary tract infections, and are little pear shaped organisms with a flagella. In Egypt, you may see schistosomia haematobium.
You don’t normally see viruses in the urine but may detect them as nuclear inclusions in cells.
A urinary cast is a cylindrical gel-like protein precipitate, which forms within the tubule lumen (which gives it a tubular shape). Non-cellular casts don’t have cells stuck to them, whereas cellular casts have cells stuck to them. You report them as a number per low power visual field. Certain non-cellular casts may be normal, but cellular casts are always abnormal.
112
Describe the different types of urinary casts.
* Hyaline casts are the most common, you normally see a couple of them.
* Granular casts are also common and have granules in them.
* Fatty casts have lipid in them, and are easily viewed with polarized light. Their presence is always abnormal, and are seen when tons of lipid is secreted from the kidney.
* Red Blood cell casts have red blood cells inside of the cast, and they are always abnormal and indicate bleeding in nephron (not the bladder).
* White blood cell casts have WBCs present, their presence is always abnormal, and are often due to pyelonephritis (bacteria in the kidney parenchyma itself).
* Renal tubular epithelial cell casts are always abnormal, have a muddy brown appearance, indicate injury to the tubule (epithelium sloughs off).
* Waxy casts have a cracked appearance and are associated with significant renal disease, like chronic renal failure.
* Broad casts are larger and also indicate chronic renal failure.
113
Describe urinary crystals.
Describe uric acid crystals.
Describe calcium oxalate crystals.
They form when urinary salts precipitate, which is affected by pH, temperature, and concentration. The three most common ones are uric acid, calcium oxalate, and triple phosphate.
Uric acid crystals occur in more acidic urine, and can be many shapes (needles, rhomboids) and are birefringent in polarized light. Too many are abnormal and can cause kidney stone formation, or can indicate gout.
Calcium oxalate crystals form in acidic or neutral urine (not as acidic as uric acid), small octahedron with envelope, like two pyramids stuck together. Indicate severe chronic renal failure, ethylene glycol poisoning, or abnormal oxalate absorption with bowel diseases.
114
Describe triple phosphate crystals.
Describe ammonium biurate crystals.
Describe two abnormal crystals seen with metabolic disorders.
Seen in alkaline urines, has a coffin lid shape, may be seen in infected urine with an alkaline pH.
Look like little thorny apple crystals, which also indicate bacterial infections and alkaline urine.
Cystine crystals and tyrosine crystals are seen in acidic urine. Cystine crystals indicate cystinuria due to an autosomal recessive defect in renal tubule transport. Tyrosine crystals can be seen in liver failure or tyrosinosis.
115
Describe highly irregular crystals that form in urine.
Describe some common urine contaminants.
Describe three protein tests.
These may be drug crystals (sulfa drugs, ampicillin) and can indicate renal damage.
Starch or talcum from gloves can contaminate it, paper fibers can contaminate it, pollen from the air may be present, or spermatozoa.
Microalbuminuria test detects albumin in the urine that is too small for a dipstick to measure but is still abnormally elevated. Quantitative protein measurement can measure protein when a significant amount is present. Urine protein electrophoresis can detect monoclonal proteins in the urine like plasma cell dyscrasia.
116
Describe how you differentiate between urine bacterial contaminants and bacterial infection.
Define ARF and AKI.
A bacterial infection will also be seen with leukocytes, whereas pure bacteria without leukocytes in the urine is likely just bacterial contamination.
Acute renal failure describes a sudden decrease in GFR. Acute Kidney Injury is a sudden decrease in renal filtration function, which implies reversibility. The higher the serum creatinine the more severe the AKI staging.
117
Describe pre-renal and intrinsic AKI.
There are three types (pre-renal, intrinsic / renal, and post-renal injury). Pre-renal AKI means the kidney is in tact but less blood flow reaches it, including volume depletion (burns or diabetes insipidus), reduced CO (heart attack), afferent arteriole constriction (calcium), efferent arteriole dilation, systemic arteriole dilation (sepsis), and renal artery occlusion. This can lead to intrinsic or renal AKI, which means the kidney itself has structural or functional damage, most commonly acute tubular necrosis (ATN), or vascular obstruction / malignant HTN / transplant rejection / glomerulonephritis / Goodpasture syndrome where antibodies attack basement membrane / metabolic issues / cytotoxic drugs / acute interstitial nephritis (AIN) which is mostly due to drugs. Inflammation usually ends up causing the end damage, lots of interleukins.
118
Describe the effect of ischemia on the tubules in intrinsic AKI.
Describe post-renal AKI.
This causes damage to the actin cytoskeleton, loss of polarity, cell death, tubule destruction, and filtrate backleak.
Post-renal AKI impedes the flow of urine, such as ureter obstruction (kidney stones or tumors), bladder obstruction (BPH / prostate cancer), or urethral obstruction (tumor). This causes urine to back up and damage the kidney, which ***inflammation*** mediates.
119
Describe some markers of AKI.
Describe the long term implications of AKI.
Inflammation associated markers indicate AKI.
• NGAL indicates neutrophils in the kidney.
• KIM-1 (kidney injury molecule) indicates phagocytosis.
• MCP1 (monocyte chemoattractant protein) is a chemokine for macrophages.
Although AKI has significant mortality, it can have complete recovery. Return of normal renal function is expected, but it can lead to chronic kidney disease.
120
# Define CKD.
Describe what affects staging of CKD.
Describe the role of protein in CKD pathogenesis.
Describe some causes of CKD glomerular damage.
* Chronic kidney disease is a progressive deterioration of renal function (GFR) longer than 3 months.
* The severity of the GFR decrease indicates kidney failure stages.
* Leakage of protein into urine kills PCT cells through endocytosis, causing injury to the tubular epithelium.
* Hypertension (whereas acute kidney injury is due to lower pressure), angiotensin II that damages cells, immunologic injuries from complement system or autoimmune complexes, metabolic injury from glucose / lipids breaking the barrier, or genetic defects like Alport syndrome (type IV collagen mutation).
121
Describe the role of podocytes in CKD.
Describe the role of the basement membrane.
Describe glomeruloserosis.
Describe some common structural features of CKD.
Podocytes can detach, apoptose, or hypertrophy.
The basement membrane can thicken in CKD, and its composition also changes thus altering its filtration.
Glomerulosclerosis means that the ECM and cells expand and proliferate, leading to decreased barrier function.
Loss of renal cells, fibrosis (glomerulosclerosis and tubulointerstitial fibrosis), and immune infiltration.
122
Describe some mechanisms for tubule damage in CKD.
Describe some mediators of CKD injury.
Describe tubulointerstitial fibrosis.
Describe vascular injury in CKD.
Metabolic injury to tubule cells when excess metabolites filtered through, ischemic injury when interstitial fibrosis moves tubules further from vessels.
TGF-beta (fibrogenic cytokine and pro-inflammatory) causes fibrosis.
Tubulointerstitial fibrosis increases synthesis of ECM, inflammation, and damage to the parenchyma.
Metabolic issues / autoimmune issues / ischemia causes endothelium and smooth muscle apoptosis, which causes capillary rarefaction (decrease in capillary density), fibrosis impairs their diameter / tone adjustment, and therefore hypoxic regions of the kidney.
123
Describe hypoxia in CKD.
Describe the KDIGO acute kidney injury staging system.
Hypoxia is a major mediator of CKD, it activates the HIF-1-Alpha transcription factor that upregulates TIMP-1 (tissue inhibitor of metalloproteinase 1) to reduce ECM turnover, lysyl oxidase to increase ECM cross linking, and collagen I (makes more matrix directly).
It has three stages, defined either by serum creatinine or urine output. Stage 1 means serum creatinine has increased by 1.5 times or UO is under 0.5 ml/kg/hour for 6 hours, stage 2 means 2 times serum creatinine or UO is under 0.5 ml/kg/hour for 12 hours, and stage 3 means serum creatinine is 3 times baseline or UO is below 0.5 ml/kg/hr for 24 hours (or complete absence of urinary output for 12 hours).
124
Describe anuria and oliguria.
Describe two multi-organ renal failure syndromes.
Anuria is urinary output (UO) below 100 mL per 24 hours. Oliguria is slightly less severe, or less than 400 mL per 24 hours.
Cardiorenal syndrome and hepatorenal syndrome, which are pre-renal causes, cause volume overload in the body (heart backs up blood or liver backs up blood). But because the blood doesn’t reach the kidneys, they hold on to salt and water (thus urine looks like they are dehydrated but visually have fluid overload).
125
Describe some small vessel diseases that can cause intrinsic acute renal failure.
* Thrombotic microangiopathy (clogs up the capillaries and harms kidney).
* Renal atheroembolism (coronary artery disease atherosclerotic plaque breaks free from a heart procedure, which slowly increases creatinine after a week).
* Small vessel vasculitis must be seen by biopsy but some blood markers can help (C-ANCA increases in blood in Wegener’a granulomatosis, and P-ANCA is seen in microscopic polyangitis).
126
Describe kidney diseases that can cause low complement.
Describe some causes of acute tubular necrosis.
Describe causes of acute interstitial nephritis.
Lupus nephritis, post infectious glomerulonephritis, and membranoproliferative glomerulonephritis.
Ischemia, toxins, rhabdomyolysis, or radio contrast agents can cause acute tubular necrosis.
NSAIDS can cause acute interstitial nephritis, antibiotics (penicillin, cephalosporin), as well as chronic infection.
127
Describe the causes of intratubular obstruction.
Describe oliguric renal failure.
Describe non-oliguric renal failure.
Intratubular obstruction can be caused by cast nephropathy (Bence Jones proteins from multiple myeloma which must be treated with a lot of hydration to flush the kidney), drugs, and crystalluria (calcium oxalate crystals from ethylene glycol).
Oliguric renal failure has under 400ml per 24 hours, due to trauma or sepsis which reduces urine output.
Non-oliguric renal failure has over 400ml per 24 hours, which could be from medications and contrast.
128
Describe the effect of ACE-I on perfusion pressure.
Describe the regions of the nephron that are susceptible to ischemic injury.
Ace inhibitors (lisonopril) will lower the production of angiotensin II, thus the efferent arteriole is less constricted lowering the intra-glomerular pressure. This helps by avoiding proteinuria (lower pressure avoids proteins squeezing out), but it can cause kidney necrosis by dropping pressure too much.
The S3 segment of the PCT and the medullary thick ascending limb are vulnerable to ischemic injury (they have high metabolic demands and low oxygen supply).
129
Describe the stages of ATN.
* Pre-renal phase: you find volume depletion and oliguria (signs that renal perfusion is lower).
* Initiation phase: creatinine increases, and renal tubular epithelial cells begin to die forming casts.
* Extension phase: creatinine increases further, oliguria becomes anuria, muddy brown granular casts form.
* Maintenance phase: the creatinine reaches a plateau, polyuria begins to occur (lots of urine)
* Repair phase: creatinine returns to a normal baseline, and the urine concentration returns to normal.
130
Describe some nephrotoxic agents.
Anti-hypertensive drugs (by lowering BP too much), diuretics (by overwhelming kidneys with fluid), NSAIDS, ACE inhibitors (efferent arteriolar vasodilation by lowering angiotensin II), contrast agents (afferent arteriolar vasoconstriction), or drugs that cause thrombotic microangiopathy (cyclosporins, clopidogrel, oral contraceptives), or drugs that can cause rapidly progressive glomerulonephritis (RGN) such as (hydralazine, D-penicilamine), cisplatin for chemotherapy, heavy metals, things that can cause interstitial nephritis (NSAIDS, thiazide diuretics, Loop diuretics, allopurinol), or things that obstruct tubules with crystals (acyclovir, ethylene glycol).
131
Describe the causes of normal urine in acute kidney injury.
Describe how the different urine findings relate to the causes of acute kidney injury.
They will have normal urine if pre-renal, post-renal, or high oncotic pressure (dextran mannitol).
* RBC casts - glomerulopathy / vasculitis / thrombotic microangjopathy
* WBC casts - pyelonephritis (will also show bacteria due to infection)/ interstitial nephritis (will not show any bacteria due to lack of infection)
* Eosinophils - allergic interstitial nephritis
* Pigmented casts - acute tubular necrosis (muddy brown casts) / myoglobinuria / hemoglobinuria
* Crystalluria - drugs / uric acid
* Non-albumin proteinuria - plasma cell dyscrasia
132
Describe diagnostic indices of pre-renal and renal failure.
When does most AKI resolve?
Pre-renal (kidney is normal thus holds on to salt and water so high SG, low fractional excretion of sodium / urea / uric acid.
Renal (kidney is not working) thus dumps lots of material so low SG, high fractional excretion of sodium / urea / uric acid.
1 month.
133
Describe the management of acute kidney injury.
Describe how you would treat hyperkalemia.
If they are oliguric, look at their volume and try to correct the underlying issue. If volume depleted, try fluids. If they have volume overload, use diuretics. If they don’t respond, then reassess their status, and consider adding more thiazide to help with urination or even dialysis (you give them diuretics to make them urinate).
Restrict their dietary potassium.
134
Determine how you would fine the rate of PAH secretion from the following data:
```
Plasma inulin concentration - 2 mg/mL
Urine inulin concentration - 100 mg/mL
Plasma PAH concentration - 0.02 mg/mL
Urine PAH concentration - 5.0 mg/mL
Urine flow - 2.0 mL/min
```
If the plasma inulin concentration is 2mg/mL, whereas the urine inulin concentration is 100mg/mL, it was concentrated 50 fold into the urine simply after filtration.
Therefore filtration should concentrate the PAH by 50 times, so if the plasma PAH is 0.02 mg/mL, it will be 1 mg/mL in the urine after filtration has occurred.
135
Lipid filled casts arise from what?
Muddy brown casts result from what?
Waxy casts result from what?
Rhomboid shapes crystals are made of what?
Dumbell and enveloped shaker crystals are made of what?
Coffin lid crystals are made of what?
Hexagonal crystals are made of what?
Blooming asbestos looking crystals are made of what?
Nephrotic syndrome
ATN
Chronic renal disease
Uric acid
Calcium oxalate
Triple phosphate
Cystine
Sulfa drugs
136
What metrics indicate pre-renal failure?
What metric indicates ATN?
What term describes urine appearance in interstitial nephritis?
Rhabdomyolysis will have ______ blood results, but what will be absent.
BUN / creatinine over 20 (because creatinine is low in pre-renal failure). FeNa under 1 is pre-renal (because fractional excretion of sodium is low).
FeNA (because fractional excretion of sodium is high).
Sterile pyuria (WBCs but no bacteria).
Positive, RBCs.
137
What is worse, creatinine increase from 1 to 1.3 or from 3 to 4? Why?
Why must you catch sudden loss in GFR soon?
Name two factors indicating a higher GFR level for a given creatinine level.
What does the GFR creatinine equation for CKD require?
Chronic kidney disease will increase what urine level? It will increase what dangerous outcome? CKD will also significantly increase risk of what? What occurs because of this?
1 to 1.3, because creatinine rises exponentially with decreasing GFR, thus 1 to 1.3 represents a huge decrease in GFR, whereas 3 to 4 is only a slight decrease in GFR
If nephrons begin to die off, they cannot be replaced (although they are very resilient).
Being male and African American.
Stable creatinine (suddenly changing creatinine is more indicative of acute kidney necrosis not CKD).
Proteinuria, all cause mortality, cardiac arrest, half of stage 3 CKD patients die of cardiac arrest before they make it to dialysis.
138
Describe some signs of CKD.
Describe the indication of polycystic kidney disease.
CKD can cause what bone disease? Describe a painful disease that occurs with super high calcium levels.
Persistent creative elevation, loss of renin thus normochromic / normocytic anemia.
Gradual decrease of GFR over years as mass effect increases, slightly faster than age related decrease of GFR, thus a type of chronic kidney disease.
Mineral bone disease (damaged kidneys cause less phosphate secretion into the nephron, thus hyperphosphatemia, thus increased PTH to try to secrete it into kidneys, and hypercalcemia, so treat with oral phosphate binders). Super high calcium where calciphylaxis causes skin to fall off, pain is impossible to manage, and has a 60% mortality rate.
139
Describe a huge issue with CKD that must be managed.
What is a normal RBC amount in urinalysis?
What is the only thing with RBC casts?
CKD increases blood pressure due to fewer nephrons, thus you must manage hypertension in CKD patients (which is why many have cardiac failure). So give them antihypertensive drugs and diuretics, and also inhibit the RAAS system (ACE inhibitors or angiotensin receptor blockers).
0-2 RBCs per high powered field (any more than this and you can assume there is bleeding somewhere).
Glomerulonephritis (RBCs may be seen in other conditions but they only form RBC casts in glomerulonephritis).
140
How do you treat CKD anemia?
Name two independent risk factors for Cv disease.
What drug of choice is used for CKD to reduce hypertension? If this doesn’t work, then what do you give them as a second line?
Describe the similarities and differences between contrast induced nephropathy and athero-embolic disease.
Start them on erythropoietin stimulating agents and titrate hemoglobin to 10-11 (whereas higher levels like 13-15 increases blood viscosity and can kill the heart). But they must have enough iron (transferrin saturation above 20%) or else ESAs will not work anyways because iron is too scarce.
CKD (by raising blood pressure) and albuminuria (due to super high glomerular capillary pressure).
Lisinopril (because you have to lower the blood pressure), ACE inhibitors
Both increase creatinine and create muddy brown casts, but contrast will increase creatinine in 48 hours whereas athero-emboli disease increases creatinine in 1 week.
141
Prerenal azotemia will have what kinds of symptoms?
Describe a very strong indication for dialysis.
List the indications for dialysis.
What does Hansel’s stain positive mean?
When and how do you use the Dell-Winters formula?
Volume depletion symptoms (diarrhea, vomiting, bleeding).
Hyperkalemia (as high blood potassium can easily put them into cardiac arrest).
AEIOU — acidosis, electrolyte abnormality (hyperkalemia), intoxication (ethylene glycol), overload, uremia (lots of urea in blood).
Eosinophils are in the urine (interstitial nephritis).
To find out how much PaCO2 should be present after compensation.
142
Describe how to find AGMA, with secondary respiratory alkalosis, and tertiary metabolic alkalosis.
Find expected AG (corrected for albumin), then find actual AG, if actual AG is too high you have AGMA, then use winters formula to see what CO2 level we expect to see, then calculate actual Co2 (and if it is too low, too much CO2 is being breathed off thus secondary respiratory alkalosis is occurring), then look at delta delta, and if this is large number, it means bicarbonate was not removed as much as you thought it would be, thus tertiary metabolic alkalosis.
143
Describe what maintains hypokalemia and alkalosis in nasogastric suctioning.
When would IV placement not be used for hypokalemia?
Chloride is being sucked out via stomach acid, thus creating hypochloremia in the blood, which somehow results in the kidneys reabsorbing tons of bicarbonate and secreting tons of potassium. Thus hypochloremia causes metabolic alkalosis through a tubular mechanism.
If you don’t see ECG changes, give them oral potassium instead of IV potassium (which can easily stop their heart).
