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
Up to what size, do molecules pass freely through the glomerular filtration?
Up to 10,000 Da
Between 10,000 → 60,000 increasing restriction
*Electrical charge of macromolecules also influences restriction
- Negatively charged molecules are repelled by HSP
- Positively charged molecules (such as dextrans) are allowed to pass faster than neutral molecules of the same size
→ No restriction by the endothelial cells
→ Charge restriction by Heparan sulfate proteoglycan + size restriction at the GBM
→ Additional restriction by the epithelial cells at the filtration slit diaphragms
