Renal Systems Flashcards
Effective osmolality equation (calculate in renal patients like you would do AG or winters. Don’t skip on this equation). Normal range:
2 (Na+ plasma) + (plasma Glucose/18)
Normal range: 285-295 mOsm/kg serum H2O
Body’s default physiologic state
Conservation (antidiuresis)
AVP (ADH, Vasopressin)
Arginine vasopressin: Works to increase bp. Secreted from posterior pituitary. Triggers Aquaporins
Where is most fluid stored?
In the cells (intracellularly). Note that the least amount of fluid is stored in blood. Also note Oxidation of carbs, protein, and fats produces water. (eating food, and drinking it gives us water)
How do we lose water?
Urine, FECES, sweat, respiratory. Note that we MAY or MAY NOT know we are losing it.
Why is intracellular and interstitial (1st and 2nd place respectively) water important?
They act as reserves in cases of low bp and blood volume
What is special about effective circulating volume (ECV)?
Effective circulating pressure is approximately equal to perfusion pressure. ECV is the pressure sensed by baroreceptors and afferent arterioles (kidneys) in the carotid sinus. We can’t sense volume, so we sense pressure instead.
What 3 things contribute to venous return? Difference between stressed and stressed volume.
Mean systemic filling pressure (Pmcf), RA pressure, and vascular resistance Stressed becomes stressed volume. Used to generate perfusion pressure.
Pathway of congestive heart failure in euvolemic patient. 1. Heart fails. Note: ECF = plasma + interstitium. Cost and benefit analysis of this compensatory pathway
- Decreased CO.
- Reduece effective circulating volume due to low pressure at baroreceptors
4.Compensation by fluid retention at kidneys (note sns did not kick in to increase hr and inotropy for an increase in perfusion) - Expansion of extracellular fluid volume depletion in face of increased extracellular volumes
End result: EFFECTIVE volume takes the L (less blood is in circulation). However, there is an increase in plasma and extracellular volume (edema).
Benefit: increased intracardiac filling pressure (RAP).
Cost: Volume overload and pulmonary/peripheral edema
Osmole
Total particle in solution. Effective osmoles creates osmotic pressure, used o drive fluid direction
Main (MOST) effective osmole
Na+. NEEDS an active transport (which is why it’s so effective). Effects body water distribution.
What is an effective osmole?
Osmole which stays in compartment unless transported by active transport into another compartment. Tends to hold onto H2O in the compartment that the osmole lives.
Describe glucose as an osmole
Effective osmole. Needs primary or secondary active transport. Does not create large osmotic gradient like Na+ (most of glucose is in muscle or brain, so it doesn’t have a deep enough squad to do so). If you screw up Glucose re-uptake (insulin deficiency or resistance) in blood, it stays there
Describe BUN (blood urea nitrogen) as an osmole
Ineffective. Lipid soluble, so it readily equilibriates between plasma membranes,
Plasma: Na+ K+ Cl- Glucose (F) BUN Osmolality Specific gravity
Plasma: Na+ 136-145 meq/L (140) K+ 3.5-5.0 meq/L (4) Cl- 98-106 meq/L (100) Glucose (F) 75-115 mg/dl (<110) BUN 10-20 mg/dl (10) Osmolality 285-295 mOsm/kg (290) Specific Gravity (1.005 - 1. 030)
Why do you need Na, K, Cl, and Ca? How does water fit into this?
All of these ions ore osmoles used to keep H2O in the body. Separately, they deal with electrophysiology (Na and K), Acid Base (Cl-), and Contractility (Ca)
Na flows (in/out) K flows (in/out)
Na flows into cell, K flows out
Describe the blood path from the renal artery, bypassing proximal tubule. Job of peritubular capularies
Renal artery –> Afferent arteriole –> glomerulus –> efferent arteriole –> vasa recta –> renal vein
Peritubular caps. are ion destination during reabsorption/ ion source during secretion. They also keep kidneys alive.
Job of glomerulus
Filtration. 100%. Nothing else. Filtration occurs no where else either.
What gets filtered in glomeruli?
Everything, including small proteins (albumin). 100% of albumin is reabsorbed in a normal glomeruli. Same as RBCs.
Job of secretion
Osmoles from the efferent arteriole, peritubular caps., or just interstitium are transported INTO the lumen of the proximal tubule to become a part of forming urine.
Job of reabsorption
Opposite of secretion. Moving stuff from forming urine in proximal tubule into the interstitium (efferent arteriole) to eventually, likely, become of the the blood circulation
What creates filtration barrier of glomerulus?
Podocytes and their foot processes, as well as filtration slits.
Describe filtering fate of the following osmoles:
- Most proteins
- Inulin (NOT INSULIN!)….note that this is no longer used to measure kidney function
- Urea
- Glucose
- Creatinine (kidney function measuring standard)
- Most proteins - NOT filtered. Clearance through gfr = 0 (as in, you will NORMALLY not find this in urine)
- Inulin (NOT INSULIN!) - Filtered. Not reabsorbed, Not secreted. Clearance therefore = GFR (100% of the cleared inulin will be found in the urine)
- Urea - Filttered, partially reabsorbed. Clearence is therefore less than GFR
- Glucose - Filtered, completely reabsorbed. Clearance = 0 (will NOT find in urine, NORMALLY)
- Creatinine - Filtered and secreted. Clearence is about the same as GFR
Standard gfr.
What level gfr equates to kidney failure?
60 minimum for ANY age. Men have higher gfr than females.
Kidney failure gfr: less than 15 (dialysis or kidney transplant suggested)
Scenario: Protein found in urine, but gfr is lit (100). Reason:
Kidney is screwed up/kidney damage. Remember, no protein is filtered through glomeruli.
Formation of creatinine. normal amount:
Cratine phosphate -> Creatine –> metabolized to form creatinine, which is freely filtered in glomeruli. NOT reabsorbed, Some is secreted. Normal volume: 0.5-1.5 mg/dl
Relative creatinine of a vegetarian? Male? Obesisty?
Creatinine filtered is higher in male than female. Vegetarians have lower creatinine levels. Note that it is a function of protein metabolism. Also note that creatinine levels are effected by race among other things. Creatinine levels have ZERO correlation to obesisty. Note that ketoacidosis patients have higher creatinine levels
Difference between BUN and Creatinine?
BUN (normal = 10-20) is a function of hydration status. Creatinine is a function of glomeruli status. They tend to be similarly affected though. If one goes up, expect the other one to go up too. Also, it’s assumed creatinine production was steady during measurement. Like, no diet changes or something lie that
Filtered load vs fractional excretion
Filtered load: amount of substance filtered per unit of time (GFR function. Fraction excretion = ratio of amount of the substance that is actually excrete in urine compared to its filtered load…as in, it accounts for reabsorption)
Most influential pressure in renal capillaries? Where is highest and lowest pressure located?
- Hydraulic pressure of blood entering renal artery and afferent arteriole = highest pressure
- Lowest pressure is in renal vein. Note that glomerulus capillaries dramatically lower pressure because of the vascular smooth muscle in the afferent arteriole
Describe result of glomerular scenario: 1. Constrict afferent 2.Constrict efferent 3.Constrict both afferent and efferent. Note that baseline glomeruli pressure is 40-50
- Constrict afferent - GFR decreased, renal blood flow decreased (blood is not making it to efferent)
- Constrict efferent - GFR increased, renal blood flow decreased (blood still not getting to efferent)
- Constrict both afferent and efferent (high sns tone): GFR stays about constant (but less than basal), renal blood flow still decreased
What’s the consequence of only a small amount of albumin being filtered through glomeruli?
Efferent blood has less h20 and volume (lowers its hydraulic pressure) and a ton of albumin…meaning high oncotic pressure. Note the low pressure in the peritubular capillaries (efferent arteriole side), as compared to the higher pressure in the proximal tubule (hydraulic pressure gradient). Result: high pressure of interstitial fluid (from proximal tubule) plus high oncotic pressure from the albumin in the peritubular capillary fosters a high drive of fluid out of the proximal tubule and into the peritubular capillary.
Kidneys prefer to increase gfr instead of shuttle blood into circulation in time of lower bp BECAUSE….How do the kidneys do this?
You need an optimal gfr pressure in order to reabsorb vital osmoles like Na and K, which are both used to maintain bp. Kidenys do this by summoning Renin Angiotenin Aldosterone System
How do kidneys sense high bp? (slide 58)?
Sensed as a result of increased GFR. This correlates to high NaCl concentration as blood enters THICK ASCENDING LIMB and passes macula densa . Note that the elevated bp would increase the gfr (the notable factor), and the resulting blood would flow through proximal tubule to thick ascending limb before actually contacting the macula densa.
How do kidneys respond to increased gfr?
Summons macula densa, which has receptors for NaCl. Upon high NaCl, macula densa secretes vasoconstrictors, which vasoconstrict AFFERENT arteriole, thus reducing gfr and subsequently reducing flow proximal tubule and thick ascending limb.
Are the kidneys innervated by psns? Does the kidney talk to the brain?
- Hell no. SNS only fam, which triggers vasoconstriction, renin secretion, Na reabsorption .and h2o reabsorption
- Yes, the kidney talks to the brain (has afferents to the brain)
Goal of RAAS
Regultate fluids to regulate bp to maintain perfusion pressure. You cannot survive with low bp. Only high bp or normal bp.
Describe job of endothelial tissues of glomerulus.
- Releases prosteglandins and nitric oxide to promote vasodilation of the AFFERENT arteriol’s vascular smooth muscle.
- Produces antiotensin II, which binds to AT1 receptor, specific for vasoconstriction, of the Efferent arteriole.
Describe angiotensin biochemical pathway
. ANgiotensinogen is converted to Angiotensin I (AI) through the rpesense of RENIN (secreted by the kidney’s juxtaglomerular cells). AI is converted to AII by angiotensin-converting enzyme (ACE). This is done by essentially all organs (brain, heart, proximal tubule brush border, etc). Now that AII is made, it can bind to either AT1 receptors or AT2 receptors.
How does one kill renin production? AII production? How does one stop AT1 binding?
- Kill with a renin blocker (Aliskiren)inhibitor
- Kill with an ACE inhibitor (Enalapril, lisinopril, or captopril)
- Use angiotensin receptor blockers (losartan or irbesartan)
Note that all of these drugs exist to cut off RAAS in some way. The mechs are all different. You must know the difference
What is the job of ACE 2?
Likely causes AII to create Angiotensin 1-7, which binds to Mas Receptor, which leads to vasodilation, diureissis/natriuresis, increase concentrations of nitric oxid and bradykinin, and an anitfibrotic
Describe job of juxtaglomerular (JG) cells
In times of low bp, it creates renin in macula densa, which converts angiotensinogen to AI in peritubular cells of proximal tubule. AI is converted to AII via ACE. AII then acts as a negative feedback to renin, so that renin can stop activating angiotensinogen.
What does glomerulus do in times of low bp? How is the glomerulus able to do this? Consequence of low gfr:
Triggers AII production, which vasoconstricts the EFFERENT side, decreasing renal bloodflow and maintaining/increasing GFR because it fosters renal REABSORPTION later on). It can do this because efferent arteriole is filled to the brim with AT1 receptors. Note that low GFR would lead to kidney ischemia…death sentence.
What are the jobs of AII?
- Vasoconstricts efferent side to increase/maintain gfr
2. Call upon aldosterone production to foster Na reabsorption
How are the heart, anterior pituitary, and kidneys effected in low bp?
Heart: Low systemic bp reaches RA and signals low pressure baroceptors, calling sns to create AVP (ADH)
Anterior Pit: SNS is called upon, along with osmoceptors and SNS and the face that there is now too much NaCl and not enough fluid, in order to secrete ADH
Kidneys: Low volume conveyed as low renal bp activates ras. Ras increases gfr and summons aldosterone.
Are there ever cases where SNS, AII, and AVP are strong enough to triggor arteriole constriction which lowers, instead of increases, gfr?
Yes (and it also lowers renal blood flow). Only increase where one must preserve the systemic bp. In such cases, the system also uses AVP and AII to retain more Na and AVP specifically antidiuresis in order to retain fluid volume and ultimately systemic bp. end goal is to reestablish RA , preload, and cardiac output.
Effects of AII binding to AT1
Stimulates vasoconstriction, Na reabsorption inside kidneys. Outside of them, it causes vasoconstriction and aldosterone secretion. Overall fosters conservation
Effects of AII binding to AT2. Note pathway is not confirmed. What is the theory behind AT1 antagonsits (losartan, valsartan)?
Bradykinin secretion which leads to natriuresis. it also triggers nitric oxide production, which vasodilates. End goal for these is elimination. Theory of AT1 antagonists is that it triggers AII binding to AT2 instead, which leads to these listed effects.
What happens if you cut off AT1 receptors with Angiotenson receptor blockers (losartan, valsartan)
Plasma renin activity will still increase because the body will still sense low bp. That means, AII will still be produced. However, if AT1 is blocked, AII would bhave no choice but to bind to AT2, which causes natriuresis and vasodilation or efferent arteriole (thoeretically)
Job of aldosterone? Why it’s bad for you?
Secreted from kidneys. Leads to Na conservation since its a mineralcorticoid. Also leads to K+ eleimination (must know this part. Na and K are in an antiport). Problems with it:hypertension, fibroblasts in heart, reduces baroceptor sensitivity, induces cardiomyocyte apoptosis/
Job of AII. Consequences:
II leads to vasoconstriciton and aldosterone secretion, but problems include glomerular damage, hypertension, left ventricular hypertroph, fibrosis in kidneys and hear, and atherosclerosis. If anythign good coem from it, it is assumed that AII binded to AT2 instead of AT1. AT2 binding leads to bradykinin for vasodilation, as well as possible reversing/blocking fibrosis to the heart and kidneys and being an antiinflammatory.
Important goals of kidneys. Note what happens in physiologically (daily) low bp.
Maintain O2 delivery and maintain hydrostatic and oncotic pressure for reabsorption. Note that in physiologically low bp, afferent arteriole baroreceptors sense this and trigger vasodilation prostoglandins on arteriole side as well as RAS (triggers vasoconstriction on efferent side) in order to maintain GFR since reabsorption is more important.
What happens to kidneys in pathologically low bp?
Constriction of afferent arterioles VIA A1 receptor SIGNALING. In other words, GFR takes the L for the greater good of the systemic bp. Consequence is that reabsorption gradients in kidneys between intratubular and peritubular flows suffer. renal blood flow tanks and renal ischemia can result
Causes of renal hypertension
IMPAIRED CARDIAC OUTPUT (note that 20% of your blood live in the kidneys at any given time)
Volume depletion
RENAL ARTERY STENOSIS (note that the kidneys would read this as low bp and signal renin…)
drugz
Job of proximal tubule. Explain osmole transportation in proximal tubule.
Main job: Na and Glucose reabsorption
Paraccellular flow: H2O and Na flow from forming urine into interstitiom
Wall adjacent to forming urine: SGLT synporter brings in glucose and Na. In addition, AII (AT1 receptor binding) fosters NHE antiporters which secrets H into forming urine and reabsorbes Na into the epithelial cell cytoplasm (note how this regulates pH)
Wall adjeacent to intersition: GLUT transporter reabsorbds glucose. AII fosters Na/K ATPase reabsorbs Na into circulation and secretes K into the cell epithelium. K and Cl synporters reabsorbs K and Cl into interstitium (note that the charges cancel).
Na and HCO3- synporter reabsorbsNa and HCO3 into interstitum (again, note that the charges cancel).
- Note* Every times H is secreted into lumen of proximal tubule, HCO3 is formed.
- Note* Na is never secreted. It is alwasy being reabsorbed. It is secreted once o the wall adjacent to the interstitum, then reabsorbed again. This happens later in the nephron.
Job of loop of henle
Na reabsorption from ascending limb. Further concentrates urine in the renal medulla. Note that it is impermeable to water, so no water is reabsorbed. Na is reabsorbed from the ascending limb.
