PH, BG, PR Flashcards
Physiological functions of mineralocorticoids
- Increase sodium and water uptake.
- Increases blood glucose.
Analysis of acid base status
.
Cell types in the nephron properties of principal cells
Principal cells reabsorb NaCl, water into the blood and secretes K into the lumen. This reabsorption of Na yield a negative lumen which drives the absorption of Cl.
Comparison of the clearance of a substance with inulin clearance
Clearance of inulin is equal to GFR: (Cx/Cinulin)=(Cx/GFR)
If Clearancex = 0-1 → lower than GFR (inulin) = ABSORBED
If Clearancex = 0-5 → higher than GFR (inulin) = SECRETED
Control of renin release in kidneys
Renin released to INCREASE blood pressure to the kidneys. If there is too little pressure, renin activates the angiotensin pathway. If there is too much pressure, this happens:
↑ GFR = ↑ NaCl to macula densa = Macula densa cells begin uptaking NaCl via with Na/Cl/K symporter = ↑ of ATP and ADO(inactive ATP) in the cell = ATP binds to P2x receptor* andADObinds to A1 receptor* (on arteriole) = ↑ Increase in calcium of Afferent Arteriole = CONTRACTION = ↓ GFR & ↓ RENIN
Compensation of respiratory alkalosis
BE = NEGATIVE for compensation
1 HCO3 / 10 pCO2
Factors affecting O2 affinity of the blood
Hydrogen ion: as H concentration changes, O2 affinity changes because hydrogen ions bind. High Hydrogen shifts the equilibrium and dissociation curve to the right. Low H shifts the equilibrium to the left.
Carbon dioxide: High PCO2 lowers the affinity (right shift).
Calculation of filtration pressure
.
correction of metabolic acidosis
base required = -BE x 0.3 x body weight
1 HCO3 / 10 pCO2
correction of metabolic alkalosis
base required = +BE x 0.2 x body weight
1 HCO3 / 10 pCO2
Effects mediated by constriction of renal afferent arterioles
- Changes in afferent arteriolar resistance: ↓ resistance ↑ PGC and GFR….↑ in resistance ↓ both.
- Changes in efferent arteriolar resistance: ↓ resistance ↓ PGC and GFR
- Changes in renal arteriolar pressure (secondary to changes in MAP): ↑ blood pressure ↑ PGC (which enhances GFR), whereas ↓ blood pressure ↓ PGC (which reduces GFR).
- Constriction of the afferent arteriole (A) decreases PGC because less of the arterial pressure is transmitted to the glomerulus, thereby reducing GFR.
- In contrast, constriction of the efferent arteriole (B) elevates PGC and thus increases GFR. Dilation of the efferent arteriole (C) decreases PGC andthus decreases GFR.
- Dilation of the afferent arteriole (D) increases PGC because more of the arterial pressure is transmitted to the glomerulus, thereby increasing GFR.
SNS affects on renal arterioles
↑ SNS = efferent and efferent arteriolar vasoconstriction = ↓ GFR and RBF.
Not only does this allow blood volume to be redirected to more critical organs, such as the brain, the reduced GFR decreases the capacity of the kidney to filter and thus potentially excrete critical ECF volume.
Effect of ADH on osmolarity of tubular fluid
ADH is released in response to increased osmolarity in the blood (remember ADH keeps WATER)
Parameters needed for calculation of clearance
Cx= V*Ux/Px
the amount of substance cleared from blood = urine volume x amount of substance in urine / plasma concentration on substance
Substances used to determine renal plasma flow
To find RPF, find out what was coming in and going out
RPF (Pa-Pv)=V*U
RBF x (1-hematocrit)
the amount of plasma/concentration of filtrates in the blood that passes thru nephron
Tubular functionchanges in TF/P ratio for filtered solutes along the proximal tube
SODIUM CONCENTRATION DOESN’T CHANGE even though it’s reabsorbed. This is because water is absorbed with it . Inulin and Cl increase
Urine concentration and dilutionrole of vasa recta
Vasa Recta produces hyperosmotic (concentrated) urine if ADH is present
Vasa Recta produces hypoosmotic (diluted) urine if ADH is absent
Hormones that regulate calcium homeostasis
PTH increases blood Ca+ levels, decreases PO4
Calcitonin decreases Ca+ levels
Calcitriol increases Ca+ levels and PO4
Stimuli for the release of ADH
Hypovolemia
Low blood pressure
Mass balance by renal handling of a substance
Reabsorptive functions of nephron segmentsproximal tubule
Proximal tubule is permeable to water (ascending loop and distal tubule aren’t)
- First half: absorb Na+ via a Na/H antiporter and a Na/X symporter. Pump out Na out into blood and K in. Water is absorbed, leaving CL- behind
- Second Half: Absorb negative ions and also the leftover Cl. water follows = positive lumen POSITIVE
At the end of the proximal tubule: Bicarbonate and glucose and AA are low because they were absorbed. Creatinine and Urea still high. Cl slightly high.
Effections of dilation of efferent arterioles on renal hemodynamics
Efferent arteriole is AFTER the glomerulus
Glomerular pressure INCREASE because its backed up.
RPF DECREASE because of increased resistance
GFR is depends at which point you are at
Evaluation of buffer capacity
Phosphate buffer: intracellular and extracellular buffer (not available in erythrocytes!!!)
Proteins are a good buffer but are not available it has a very low intracellular concentration. They are many proteins which can be a buffer for a wide range of pHs. The one’s closest the neutral are histidine, cysteine, and ammonia.
Bicarbonate/Co2 buffer is a good intracellular buffer but not a good extracellular buffer. It can be a good extracellular buffer if it’s open to the body.
Effect aldosterone as a hormone replacement
Increase Na/H2O absorption
Can cause hypokalemia and alkalosis
Actions of aldosteroneeffects of increased plasma levels on plasma K+ and pH
Aldosterone increases K secretion across the apical membrane (there’s increased K in the tubular fluid, less in the blood)
Increased K plasma levels drive aldosterone production.
Too much aldOsterone can lead to hypOkalemia and alkalOsis.
Changes in ion concentration along the proximal tubule
Renal handling or organic anions and drugs
High AG: new unmeasured anion exogenous acid. Chlorine and low bicarbonate.
→ Examples would be lactic acidosis, ketoacidosis, chronic renal failure, methanol, ethanol, and rhabdomyalysis.
Normal AG: high chlorine replaces the lost HCO3 which is why we don’t see it.
→ Ex. Diarrhea, RTA, HCl ingestion, and CA inhibitors.
The corticopapillary osmotic gradient and urine concentrating ability
Plasma ADH levels will set the urine osmolality, high urine osmolality AND high plasma osmolarity increases thirst, through osmoreceptors increase ADH release and increase in H20 reabsorption.
Plasma osmolarity is the primary regulator of ADH release.
primary regulator of ADH release.
Plasma osmolarity is the primary regulator of ADH release.
Intestinal effect of aldosterone
Absorption in the colon is lower quantity and under fine control. Its product, fecal material, is typically quite dry containing about 100 mL of water excreted this way per day. Aldosterone increases absorption. Thus aldosterone can act on colonocytes in much the same way it does in the kidney to increase colonic fluid absorption of sodium and water therefore to maintain blood volume and pressure. The colonic response to aldosterone is not nearly as important a process for water balance as the response of the kidneys to this hormone.
Response of renin-angiotensin system to renal ischemia
Renin is secreted by the juxtaglomerular cells when the intraglomerular pressure is too low.
Angiotensin 2 upregulates the blood pressure by constricting the blood vessels and potentiating the effects of NE on vascular tone.
It releases aldosterone from the adrenal cortex.
ACE inhibitors are standard antihypertensive drugs. In addition to preventing angiotensin synthesis they also inhibit the breakdown of the vasodilator peptide bradykinin.
Also available are angiotensin receptors blockers and renin inhibitors.
Amino acid disease causing black diapers
Alkaptonuria → can’t digest tyrosine
Mutation in homogentisate oxidase
Defect in Tyrosine Catabolism
Amino acid metabolized by kidneys in acidosis
Glutamine
(EASY POINT, REMEMBER THIS)
Use of Benzoic acid and phenylacetic acid in hyperammonemia
Benzoic acid is also called hippuric acid. It provides an alternative route of nitrogen excretion
Phenylbutyrate aka phenylacetic acid removes two nitrogens at a time so it’s the preferred method.
*both of these “soak up” extra nitrogens in the body
Enzyme producing melanin
N actelytransferase
Tyrosine requirement in PKU
Tyrosine is the precursor to make phenylalanine, which is what PKU people lack
Reduction of phosphate foods in chronic renal failure
Reduction of phosphate foods in chronic renal failure
Identify defective enzyme in patient with PKU despite normal Phe hydroxylase
Other possibilities: Don’t have BioH4
OR (more likely)
dihydropteridine reductase
restriction for PDH deficiency
ALANINE
Actions of angiotensin converting enzyme
Converts angiotensin I (in lung) into angiotensin II. Angiotensin II works in the kidney to increase ADH levels, increasing water uptake.
This increases blood pressure.
Mechanism of action of drugs used to treat heart failure
Loop diuretics: Furosemide → inhibition of Na/Cl/K symporter in thick ascending loop
Adverse effects of tolvaptan
Vasopressin (antidiuretic hormone) antagonists nausea, xerostomia (dry mouth) hypotension, hypokalemia
taken at home
Molecular mechanism of action of acetazolamide
‘zolamide’
Carbonic anhydrase inhibitor; decreases bicarbonate
Urinary electrolyte porile produced by loop diuretics
Loop diurectics decrease kidney’s ability to concentrate urine
Increased renal excretion of Na, CL, K, H, Ca
Urine will be acidic
Adverse effects of furosemide
used in heart failure -loop or high ceiling diuretics
MOA: inhibiting the Na/K/2Cl cotransporter in the loop of Henle thick ascending loop specifically
Pharmacological effects: promotes excretion of NaCl, H, K, Mg, and Ca
Side Effects: hyperuricemia, hypokalemia, hypocalcemia, hypomagnesium, and hearing impairment
Diuretics used to treat nephrolithiasis
Thiazide diuretics
Pharmacological actions/effects and clinical uses of hydrochlorothiazide
MOA: blocks the action of Na/Cl cotransporter in the luminal of the distal convolute tubule
- inhibits NaCl reabsorption in the DCT
- produces diuresis
- promotes renal excretion of K and H
Adverse effects of indapamide
Indapamide is a thiazide
- Hypokalemia
- metabolic alkalosis
- Hypovolemia
Appropriate drugs for the treatment of ascites associated with right sided heart failure
Furosemide
Molecular target of furosemide
Inhibition of Na/K/Cl symporter in the ascending loop of Henle
Mechanism of action of desmopressin
V2 receptor agonist, used for central diabetes insipidus.
Can’t use it for nephrogenic diabetes because V2 receptors are unresponsive.
For nephrogenic diabetes, use thiazides.
Adverse effects of mannitol
Think of mannitol as a sugar we use to “soak up” any excess fluid in our patient (like cerebral edema)
- Adverse effect in patients with normal kidney function: extracellular volume contraction (losing too much fluid) which leads to hypovolemia, dehydration, hypernatremia
- Adverse effect in patients with cardiac or renal disease: volume expansion (because they can’t pee out the excess fluid) which can cause hypervolemia, hyponatremia, pulmonary edema
Appropriate treatment for lithium induced nephrogenic diabetis insipidus
(hint: thiazides)
Thiazides and thiazide-like:
- Hydrochlorothiazide
- Indapamide
- sulfonamides
Work in early distal convoluted tube and decrease absorption of NaCl
Mechanism of action: Thiazide and thiazide like diuretics inhibit Na/Cl symporter.
Results in reduced reabsorption of NaCl.
Some thiazides (including hydrochlorothiazide and indapamide) are also weak inhibitors of carbonic anhydrase.
Therapeutic use: hypertension, edema in the heart or kidneys, and nephrogenic diabetes insipidus (seemsparadoxicallikely mediated via extracellular volume contraction promotes proximal tubule Na and water reabsorption. Therefore, a reduced volume is delivered to the distal tubule)
Molecular mechanism of action of dorzolamide
Carbonic androhyde inhibitor → decreases the synthesis of H3CO2 (bicarbonate) from H2O and CO2
Since it works on pH we use it for any condition dealing with pH homeostasis: mountain sickness, epilepsy, alkalosis due to thiazide or loop diuretic use
Works in the proximal tubules
Use of diuretics in treatment of acute pulmonary edema
Loop Diuretics
- Furosemide
- ethacrynic acid
Inhibit Na/K/Cl symporter in (Ascending?) loop; There’s no negative charge on the lumen side so no Mg/Ca paracellular transport, no water follows.
