Chapter 2 - Applied Renal Physiology Flashcards
Three components of glomerular capillary wall or filtration barrier
- capillary endothelium
- basement membrane
- visceral epithelium
Three components of Juxtaglomerular apparatus
- macula densa (sense Na)
- juxtaglomerular cells (sense pressure in afferent arteriole, release renin)
- mesangial cell (release prostaglandin which contribute to renal vasodilation)
Two types of barrier in glomerular capillary wall
- size selective (exclude molecule with radii greater than 4 nm)
- charge selective (negatively charged sialoglycoproteins and peptidoglycans)
Charge selective, which one has greater restriction to filtration?
Negative > Neutral > Positive (i.e. Albumin is negatively charged, 3.6 nm radius)
Equation for SNGFR (single-nephron GFR)
Kf: ulrafiltration constant
Hydrostatic pressure of glmerulus minus hydrostatic pressure of Bowmans’ capsule minus oncotic pressure of glomerulus, multiply by ultrafiltration constant
Kf (ultrafiltration constant) is dependent on two factors?
- surface area available for filtration
- permeability per unit area for filtration and the permeability
Both surface area and permeability are significantly greater than capillary bed in skeletal muscle- the fact that GFR is so much higher than the movement of fluid across systemic capillaries
Effects of alteration in afferent and efferent arteriolar tone on renal blood flow and glomerular filtration rate?
- decreased resistance in afferent arteriole
- increased resistance in afferent arteriole
- decreased resistance in efferent arteriole
- increased resistance in efferent arteriole
Alteration in resistance in the afferent arteriole lead to parallel changes in GFR and RBF
Alteration in resistance in the efferent arteriole lead to divergent changes in GFR and RBF
1. increased RBF, increased GFR
2. decreased RBF, decreased GFR
3. increased RBF, decreased GFR
4. decreased RBF, increased GFR (in long term, decreased RBF and decreased GFR due to increased oncotic pressure in glomerulus)
Effects of vasoactive mediators on glomerular hemodynamics (each mediator's act on afferent and efferent) Dopamine Norepinephrine Vasopressin PGE2, PGI2
dopamine: relax afferent, relax efferent
norepinephrine, AG2: constrict afferent, constrict efferent
Vasopressin constrict efferent
PGE2, PGI2: relax afferent, relax efferent
What is ideal requirements of the molecule used to measure GFR?
Inulin: Freely filtered by glomerulus, neither reabsorbed or secreted. neutral electric charge, not protein bound, not metabolized by kidney
Where are the two major sites of resistance within kidney?
Afferent arteriole, efferent arteriole.
What is autoregulation?
Intrinsic ability of an organ to maintain blood flow at a nearly constant rate despite change in arterial perfusion pressure
In what range of perfusion pressure, kidney’s GFR and RBC minimally change?
80-180 mmHg
As pressure increases, flow can remain constant only if resistance increases proportionately. where is the site of this resistance change in the kidneys?
Afferent arteriole
What are two physiologic mechanisms contribute to autoregulation?
- myogenic mechanism (Laplace’s law: T = r x P): perfusion pressure increases, wall tension increases, smooth muscle stretch by increased perfusion. Then it constricts, thus limiting transmission of this increased pressure to the glomerulus and minimizing any change in glomerular capillary hydrostatic pressure and SNGFR
- tubuloglomerular feedback
How body obtain vitamin D (cholecalciferol)
- Diet
2. UV irradiation from skin
Kidney convert 25-hydroxycholecalciferol to ___?
Calcitriol, which isthe active form of vitamin D3
What are the two things that stimulate calcitriol synthesis?
- Hypocalcemia
2. PTH
Major effects of calcitriol?
- Increased intestinal absorption of calcium and phosphate
- permissive effect on PTH-mediated bone resorption of calcium and phosphate
- negative feedback control on PTH synthesis and secretion by parathyroid glands
What’s the main role of RAS (Renin-angeiotensin system)
defense of the ECFV (extracellular volume) via sodium homeostasis
What are “3 major stimuli” for Renin release?
- Decreased renal perfusion pressure caused by 1) systemic hypotension (<80-90 mmHg) or ECFV depletion- sensed by afferent arterioles by granular cells
- Stimulation of cardiac and arterial baroreceptors by systemic hypotension- increased symtpathetic neural activity- catecholamine- stimulate renin via beta-adrenergic receptors on granular cells
- changes in distal tubular flow and delivery of chloride
What inhibit the release of Renin?
Negative feedback loop: direct effect of angiotensin 2 on the granaular cells
How angiotensin 2 retore ECFV?
- arteriolar vasoconstriction (renal, splanchinc, cutaneous vascular bed)
- release of norepinephrine from adrenal medulla
- increased proximal tubular reabsorption of sodium by stimulating Na-H-antiporter
- aldosterone release from zona glomerulosa of adrenal cortex
- alteration in glomerular and post-glomerular hemodynamics
1) constriction of efferent and afferent (efferent more than afferent, thus filter fraction increases)
2) changes favoring salt and water rabsorption (decreases peritubular capillary hydrostatic pressure, increase peritubular capillary oncotic pressure)
3) contract glomerular mesangial cell- decrease surface area (decrease Kf)
4) stimulate release of prostaglandins from glomeruli, minimize vasoconstrictive effect of angiotensin 2
What are 3 major endocrine functions of kidney
- regulation of RBC production by bone marrow
- defense of ECFV (extracellular fluid volume)
- maintenance of calcium homeostasis
What are the end-result of chronic renal disease as far as endocrine functions?
- non-regenerative anemia
- systemic hypertension
- renal secondary hyperparathyroidism
What is the major stimluant of EPO production
decreased oxygen delivery to the kidneys
How EPO regulate red blood cell generation
EPO binds to receptors on erythroid progenitor cells in the bone marrow preventing apoptosis, and allows them toe proliferate and differentiate into reticulocytosis
T/F: some cats that initially responded to recombinant feline EPO later developed anemia that was refractory to additional treatment with recombinant feline EPO
True
T/F: use of recombinant human EPO in dogs and cats is associated with antibody formation in up to 50% of treated dogs and cats after 1-3 months of treatment.
True
