Renal Flashcards
Define Renal Plasma Clearance (RPC).
The amount of blood per unit time in which a substance is completely filtered out by the kidneys.
In relation to net secretion/absorption, what does a high RPC tell you? A low RPC?
High RPC - There is net secretion of FILTRATE occuring in the distal tubule.
Low RPC - There is net reabsorption of FILTRATE occurring in the distal tubule.
Define End-Stage Renal Disease (ESRD)
Kidney function so low that it cannot sustain life. Dialysis or transplant is needed for survival.
___% of the population has Chronic Kidney Disease.
14 % (1 in 7 people)
CKD has a high prevalence, incidence, and mortality.
The incidence of Kidney Disease increases with ___.
age.
What are common risk factors for Chronic Kidney Disease? (6)
Diabetes Obesity Tobacco Age Heart Problems/Stroke Hypertension
____ racial group is most affected by Chronic Kidney
Black/African American
What is the functional unit of the Kidney?
The Nephron
What are two major hormones released by the kidney? What do they do?
EPO - Stimulates the production of RBC’s during hypoxia
Alpha 1 Hydroxylase - Activates Vitamin D to increase serum calcium levels during hypocalcemic states.
What two factors determine blood flow through the kidneys? (think about THE equation…)
Pressure and Resistance
F = (P1-P2) / R
What are the main sites of resistance to blood flow in the nephron?
Afferent and efferent arterioles
What molecules have an easier time being filtered at the glomerulus? What molecules have a harder time?
Easier - Small (<5000 Da) and positively charged/polar
Harder - Large, negatively charged, protein bound
Why is it easier for positively charged molecules to be filtered at the glomerulus than negatively charged molecules?
Because the visceral pleura has a negatively coated charge. (double check this)
Why does Net Filtration Pressure (NFP) decrease as you move toward the efferent capillary?
Since small solutes (water, salt) pass through bowman’s capsule while proteins cannot. The oncotic pressure is increased as you move from afferent to efferent arteriole. Since oncotic pressure is a reabsorptive force, increasing it will cause less filtration.
Kidneys can regulate the glomerular filtration rate (GFR) independently of renal blood flow (RBF). Why?
Because the kidneys can utilize the efferent and afferent arterioles to modulate the Pressure of the glomerular capillary (PGC) and therefore the GFR.
What are the 2 mechanism for renal auto-regulation? Describe them.
- Arteriolar Myogenic Mechanism - Arteriolar smooth muscle senses increased stretch of afferent arteriole (from high blood volume) and vasoconstricts leading to increased resistance, decreased flow, and stable GFR.
- Tubuloglomerular Feedback - When the Macula Densa senses a high sodium concentration it causes vasoconstriction of the afferent arteriole.
How does tubuloglomerular Feedback work specifically?
Sodium from filtrate is transported into the macula densa via sodium transporter. Sodium then leaves the cell through an ATPase pump. ATP is broken down (releasing Adenosine) to activate this pump. Adenosine binds the A1 receptor on smooth muscle of afferent arteriole causing vasoconstriction.
In what part of the nephron does the most reabsorption occur?
The proximal convoluted tubule.
HUGE reabsorption of: Na, Cl, K, HCO3, & water
What is the normal osmolality of the blood?
Knowing this, at what part of the kidney tubular system does iso-osmotic filtration//reabsorption occur?
300 mOsm/L
Iso-osmotic Filtration = Bowman’s Capsule
Iso-osmotic Reabsorption = Proximal Convoluted Tubule
At what part(s) of the kidney tubular system does REGULATED secretion/reabsorption occur?
The Collecting Duct
Tight junctions are more “leaky” in the _________ portion of the nephron. Why?
Proximal Convoluted Tubule.
Because this is where a lot reabsorption occurs.
In Tubular Epithelial Cells the membrane facing the tubule lumen is the _____ membrane. The membrane facing the interstitial space/capillary is the _____ membrane.
Apical Membrane
Basolateral Membrane
What does it mean that the tubular epithelial cells are “polarized?”
That there are different types of transporter channels on each side (apical, basolateral) of the cell. This is critical to their normal functioning.
Describe the difference between Paracellular Transport and Transcellular Transport.
Paracellular - Solute goes through the tight junction between cells to travel down its ELECTROCHEMICAL gradient (always passive).
Transcellular - Solute actually goes through the cell itself
Describe Gradient Limited Tubular Reabsorption.
Large movement of solute paracellularly from lumen to interstitium. This causes some solute to move back into lumen further down the tubule because of lower concentration gradient in the lumen. Therefore reabsorption is limited by the gradient.
Describe Tubular Maximum-Limited Reabsorption.
Tight junctions are very tight so solute must move through a transporter. Since transporter can only move a given number of solute through the cell (transcellular) the reabsorption is limited by the transporter (Tmax).
Define:
Osmole
Osmolarity
Osmolality
Osmole - # of moles of free solute particles in solution
Osmolarity - Number of osmoles of solute per L solution
Osmolality - Number of osmoles of solute per kg solvent
osmolarity and osmolalilty are used interchangeably.
How does fat affect total body water?
Total body water is decreased by fat.
What is Inulin? What can it tell us and how?
Inulin is a plant polysaccharide.
It can tell us the GFR.
This is because inulin is freely filtered, not secreted, and not reabsorbed.
What is the closest thing to inulin that is used to measure GFR in humans?
Creatinine. It is only slightly secreted (10%).
What is the normal blood plasma concentration range for creatinine?
0.7 - 1.3 mg/dL
Describe the 3 biometric equations used to obtain a GFR from creatinine concentrations. Which is most comprehensive?
- Cockroft Gault - Indicated for drug dosing.
- Modified Diet in Renal Disease (MDRD) - Measures GFR in kidney disease patients.
- Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) - most comprehensive.
Describe and explain the limitations of the 3 biometric equations used to obtain GFR from creatnine concentrations.
- Cockroft Gault - Overestimates the GFR
- MDRD - Used for monitoring kidney disease; not good for screening. Underestimates GFR for normal kidney function individuals.
- CKD-EPI - Used for screening (variety of age)
All are limited by not accounting for race/gender.
Describe the difference between osmotic and oncotic pressure.
Osmotic - Movement of fluid due to dissolved substances. (Intracellular Extracellular fluid)
Oncotic - Movement of fluid due to non-dissolved substances (movement between extracellular compartments)
Does the osmolality between the ICF and ECF ever differ? Why or why not?
No. Osmolality between ECF and ICF are always the same. Osmosis will always balance out osmolality between ECF and ICF.
What affects ECF volume? Changes in sodium content or sodium concentration? Why?
sodium CONTENT: This will make someone try to increase their fluid intake (ie. via thirst). sodium concentration relates to the osmolality which would affect the ICF.
How is ECF generally assessed?
Through physical exam and sodium content.
**Urine concentration is the only lab that can assess ECF. Not typically used.
How is ICF assessed?
Labs: sodium concentration, osmolality.
What does Para-amino-hypurric (PAH) acid tell us and how?
Tells us the Renal Plasma Flow since PAH is freely filtered, 100% secreted and not reabsorbed. So whatever comes out tells us how much renal plasma flowed through the nephron.
In which part(s) of the nephron is there unregulated resorption/secretion? Which part(s) are regulated?
Unregulated: Proximal Tubule, Loop of Henle, Distal Convoluted Tubule
Regulated: Collecting Duct
How does chloride move in relation to sodium?
Chloride always follows sodium. So reabsorption/secretion of chloride depends on reabsorption/secretion of sodium.
What does “insensible” loss of water refer to?
The water we lose that we cannot really control (sweating, breathing, etc.)
What is meant by Obligatory water loss?
Since we are metabolically active, the body must lose water in order to remove generated metabolic waste. You need about half a liter of FRESH water (low osmolarity) to effectively remove metabolic waste.
At the collecting duct aldosterone regulates_____, ADH regulates____.
sodium resorption
water resorption
Which part of the nephron is considered the “work horse” of the cell? Why?
The proximal tubule.
This is where the most ATP is used (for transporters)
Why do hydrogen ions need to be recycled at the proximal tubule?
There are low levels of Hydrogen ions in the blood and therefore filtrate compared to the high levels of sodium. If you run out of hydrogen you impair sodium resorption.
At what point in the nephron is there FIRST a change is filtrate osmolarity? Why?
At the Loop of Henle. The thin descending limb only allows for water resorption; solutes cannot move which increases FILTRATE osmolarity.
ADH/vasopressin comes from the ____.
Aldosterone comes from the ____.
posterior pituitary gland.
adrenal gland.
Osmolarity is lowest in the distal convoluted tubule. Why?
Because you have more solute being reabsorbed from the FILTRATE than water.
Describe the Contercurrent Multiplier at the loop of Henle.
As filtrate moves up the loop of henle, solute leaves into the medullary space. This increases the osmolarity of he medulla which allows for water to be resorbtion. Water moves toward higher osmolarity.
Describe the Countercurrent Exchanger at the Vasa Recta.
Solutes are trapped within the lower portion (medulla/interstitium) of the vasa recta.
Solutes cycle back and forth because they are moving out of the vasa recta towards a lower concentration in the medullary/intersitial space then lower concentration back in the vasa recta.
What can “wash out” the medullary gradient?
Excess water intake. (psychosis, drowning)
What % of sodium does is each part of the nephron capable of absorbing? Proximal Convoluted Tubule? Thick ascending Limb? Distal Convoluted Tubule? Collecting Duct?
PCT - 67%
TAL - 25%
DCT - 5%
CD - 3%
Hormones can only affect what part of the nephron?
The Collecting Duct
Other tubules ARE NOT controlled by hormones!!
Define Diuretic and Naturetic; what makes these terms interchangeable?
Diuretic - Substance that increases urine production.
Naturetic - Substance that increases renal sodium secretion.
Both of these effects happen at the same (sodium secretion–> water secretion –> more urine) time which is why they are interchangeable.
What are the three main types of diuretics? Where do they each act? How do they ALL work?
Loop Diuretics - Thick Ascending Limb
Thiazide Diuretics - Distal Convoluted Tubule
Potassium sparing diuretics - Collecting Duct
They all decrease resorption filtered sodium by blocking sodium transporters.
What is the difference between hypercalcemia and hypercalcuria?
Hypercalcemia - Too much calcium in the BLOOD. (low calcium in the urine)
Hypercalcuria - Too much calcium in the URINE. (low calcium in the blood)
What can offset the effect of diuretics?
High sodium diet/intake.
What does a refractory edema refer to? What are 3 things to consider if you notice this?
- Poor GI absorption of the drug
- Decreased drug entry into tubular lumen
- Heart failure - poor perfusion increases proximal Na+ resorption.
Explain what happens to solutes at the Collecting Duct (aka “Distal Tubule”) of the nephron.
Na+: Resorbed
K+: Secreted
H+: Secreted
Explain what happens to sodium and bicarbonate at the proximal convoluted tubule of the nephron.
They are both resorbed (into the blood).
Explain what happens to solutes at the Thick ascending Limb of the nephron.
Na+, Cl-, K+, Ca2+, Mg2+ are all resorbed.
Disorders of sodium CONCENTRATION refer to an imbalance of water or sodium?
Water imbalance. Water changes the osmolarity (concentration (mg/ml) of sodium).
Sodium content (mg) changes the water volume.
How does ADH regulate water resorption?
ADH acts on the CD to stimulate insertion of aquaporins to the apical/luminal side of the tubular epithelia. This allows for water to be resorbed.
What are the two physiologic (direct) triggers for ADH release?
Low fluid volume
High osmolality
What are non-physiologic (indirect) triggers for ADH release? (3)
Pain
Nausea/Vomiting
Medications.
______ sense changes in fluid volume.
______ sense changes in fluid osmolality.
Baroreceptors
Osmoreceptors
Thirst is directly stimulated by ____ and ___ directly. It is indirectly stimulated by ___ and ___.
Low fluid volume, high fluid osmolarity.
Dry mouth, angiotensin II
How can ADH be measured in a patient? What would we see if ADH levels were high?
Patient urine osmolality.
High ADH = High urine osmolality.
What type of drugs does the liver favor eliminating?
What type of drugs does the Kidney favor eliminating?
Liver: Lipophilic, non-ionic, highly protein bound
Kidney: Hydrophilic/polar
The Kidney can freely filter substances less than ____ Daltons.
5000
What does biotransformation refer to? What organ does this and how?
Conversion of substances to something that is easier to secrete.
The liver does biotransformation by making substances more polar and hydrophilic.
Can organic cations and anions be filtered at the glomerulus for secretion? How are they secreted from the interstitium?
No
Cations: Passive movement across basolateral membrane active transport across apical/luminal membrane into filtrate of the PCT.
Anions: Active transport across basolateral membrane, passive movement across apical/luminal membrane into filtrate of the PCT.
What are the 3 types of renal reabsorption?
- Passive Reabsorption
- Active Reabsorption
- Endocytosis
Bioavailability
Refers to the fraction of an administered dose that actually gets into the systemic circulation.
ie. 70mg of drug x administered –> 70mg in circulation = 100% bioavailability.
Why is IV drug bioavailability 100%?
IV drugs go directly into the bloodstream and do not have to pass through anything else.
What does “steady state” mean in relation to pharmacology?
Rate of Drug administered = Rate of Drug excreted.
At how many half-lives (without a loading dose) is the steady state typically reached?
3 to 5 half lives
What is a loading dose? What types of drugs is it useful for?
Loading dose is a large initial medication dose given to reach the steady state concentration (Css) at a quicker rate.
When should you use a continuous infusion? When should you a multiple dose infusion?
Continuous Dose - For drugs that need constant exposure at receptors
Multiple Dose - Drugs that need a maximized plasma concentration for a short time (efficacy), but then require clearance to prevent toxicity.
What are symptoms associated with hyperphosphatemia?
Muscle cramps
Tetany
Perioral numbness
