Renal_1 Flashcards
What is the definition of homeostasis?
What does its maintenance require?
Tendency to maintain relative constancy of physiological variables
Stimulus → Receptor → (afferent pathway) → Integrative Center → (efferent pathway) → effector → response → negative loop onto stimulus
What are the characteristics of homeostasis?
- Steady-state
- Set-point (threshold at which things get activated)
- Negative feedback (sensitive to osmolarity → release hormones)
- Positive freedback (mostly in metabolic pathways)
- Error signal (when deviation from the set point)
- Physiological range
What are the advantages and disadvantages of being multicellular?
Advantage → Division of labour between different cell types can provide selective advantage → increased complexity, better adaptation to the environment
Disadvatange → requires body fluids that have a stable composition and osmolality
- Cells have to be surrounded by an environment that is homeostatically controlled
What are the 3 main functions of the kidney?
- Endocrine function
- Homeostatic function → maintain the ionic and osmotic balance
- Excretory function
What are 2 ways to maintain homeostasis?
- Lowering gradients → less work needed to maintain hemeostasis
- Lowering permeability → minimize dissipation of gradients
What are the main advatages and disadvantages of terrestrial life?
Adv → the concentration in the aire is much higher → 20.9% vs < 1% → allow higher metabolic rate and thermal regulation
Disadv → water loss (dessication)
In mammals, how did kidney evolve to allow homeostasis in very different envrionments?
- Waxy monkey frog → wax on the surface of the frog to reduce loss of water
- Water-holding frog → Enormous urinary bladder used as storage for water
LOOP of henle only in birds and mammals:
3. Kangaroo rat → Loops of Henle in the kidneys are very long to concentrate the urine (to conserve water)
*Beaver live in fresh water → no need so short loops of henle
What variables of homeostasis are regulated by the kidney?
- ECF volume
- ECF osmolality
- Acid-base status
- ECF K+ concentration
- Divalent ion concentration → bone and immune function
- Blood pressure → maintain perfusion to vital organs
- RBC mass
- Skeletal integrity → VitD and Calcium regulation
What is the order of the different parts of the nephron?
- Bowman’s capsule/space
- Proximal convoluted tubule (C)
- Proximal straight tubule (M)
- Descending thin limb of Henle’s loop (M)
- Ascending thin limb of Henle’s loop (M)
- Thick ascending limb of Henle’s loop (M/C ends at the macula densa in cortex)
- Distal convoluted tubule (C)
- Cortical collecing duct (C)
- Medullary collecting duct (M)
*Actually 4 parts: Proximal tubule → Loop of Henle → Distal convoluted tubule → Collecting duct
How do animals deal with aquatic and terrestrial environments?
Many strategies used to maintain ionic and osmotic gradients:
- reducing permeability of epithelial surfaces
- Specialized excretory organs and secretory glands
- Behavioural and other adaptations
*Kidney is the primary regulatory and excretory organ
What compounds are excreted by the kidney as an organ of excretion?
Nitrogenous wastes → DNA and RNA wastes, protein breakdown, uric acids
Dietary end products → antibiotics
Drugs and drug metabolites
Products of metabolism
What compounds/hormones are produced by the kidney?
- Erythropoietin
- 1,25-OH Vitamin D → Calcium regulation and auto-immunity
- Renin → important for generating hormones
What are the cellular components of the Glomerulus?
- Epithelial cells:
- Synthesis of matrix components
- Maintenance of capillary wall permeability by cleaning the filtration barrier
- Found in the inner surface of the bowman’s capsule → podocytes (have foot processes that rap around capillaries to allow filtration sites) - Endothelial cells:
- Synthesis of matrix components (coming from both sides)
- Found in the glomerular capillaries → regulate filtration of plasma - Mesangial cells :
- Contain contractile elements and receptors for angiotensin II (and other factors) that regulate renal hemodynamics
- Contribute to the synthesis of matrix components
- Have capacity for phagocytosis
- Fill the spaces between glomerular capillary loops
What is the composition of the basement membrane of the glomerular barrier?
- Type IV collagen → form a mesh work on which epithelial cells sit, trimeric protein (3 domains) with alpha-helical structures (different from collagen I, II, III)
- Laminin →important for cell attachement, interacts with collagen + cell, concentrated in lamina rara externa and rara interna
- Fibronectin → important for cell attachement
- Heparan sulphate proteoglycan → have negatively charged side chains (sulfate chains) → repel negatively charged proteins from being filtered, important role in filtration selectivity
Concentrated in lamina rara externa and interna (but everywhere in GBM), core protein + glycosaminoglycan
*Also has O- and N-linked carbohydrates
*All synthesized by epithelial, endothelial and mesangial cells
What are the 3 layers of the filtration barrier in the glomerulus?
Plasma
1. Endothelial cells
2. Glomerular basement membrane
3. Epithelial cells (+ podocytes)
Bowman’s capsule
Which elements are likely to be filtrated through the glomerular barrier and which are not likely?
Likely: Na+, K+, Cl-, H2O, Urea, Glucose, Sucrose, Inulin
Not likely: Lactoglobulin, Egg albumin, Hemoglobin (Proteins)
What are the 2 main forces driving filtration?
- Hydrostatic pressure → 45 mmHg (towards the Bowman’s capsule)
*Does not change much between the afferent and efferent arterioles - Colloid osmotic pressure → 30 mm Hg (towards the capillaries)
*Increases to reach the hydrostatic pressure → no net filtration pressure by the end of the glomerular capillaries (even in the 2nd half, not much filtration)
Net filtration force at the start = 15 mm Hg towards the Bowman’s space
What is the equation for the Glomerular filtration rate?
GFR = Kf * Puf = Kf (Pgc - Pt - πgc)
Puf = net ultrafiltration pressure = Pgc - Pt - πgc
Kf = filtering ability of the membrane (ultrafiltration coefficient → include hydraulic permeability, surface area)
Pgc = hydrostatic pressure in the glomerular capillaries
Pt = hydraulic pressure in Bowman’s space
πgc = oncotic pressure in the GC
*no significant Bowman oncotic pressure
What are the advantages and disadvantages of clearance?
Advantages:
- Simple
- Gives overall assessment of renal handling of the solute
- Vitrually the only in vivo method available for use on patients
Disadvantages:
- provides no info on location of transport process / mechanism
- Only provides net transport (no info about reabsorption vs filtration vs excretion or about counter-acting forces)
- Flux could be active or passive (no info)
What is the definition and equation for clearance?
Clearance is the minimum volume of plasma from which the kidney could, in 1 minute, remove all substance X.
Clearance in ml/min = [X]u * V / [x]p
[X]u = concentration of substance X in urine (mg/ml)
V = urine flow rate (ml/min)
[x]p = concentration of X in plasma (mg/ml)
*Indirect, but most practical approach to measure GFR, RPF (renal plasma flow), tubular transport functions
What are the general movements/transports of inulin, glucose, PAH, Potassium along the kidney?
Inulin → Only filtered → measure of GFR (can be compared with other substances to see if reabsorption or secretion occurs)
Glucose → Filtered and reabsorbed
PAH → Filtered and secreted (flow-limited)
Potassium → Filtered, reabsorped and secreted
What percentage of the plasma volume is filtrated at the glomerulus?
What volume do the glomeruli filter appromimately/day?
As blood flows through the glomerular capillary, 20% of plasma volume is filtered due to the pressures
Glomeruli filters approx. 180 liters/day → small fraction of the filtrate is actually excreted in urine (0.6-2.5 L)
What is the filtration fraction (FF)?
FF = GFR/RPF ~ 15%-20%
It is the proprtion between glomerular filtration rate and renal plasma flow rate → not fixed, but may vary depending on the magnitude of GFR, the composition of the blood, condition of the glomerular capillary
