physiology Flashcards
Average input and output in a day?
- 2500 in and 2500 ml out in: metabolism 10% foods 30% beverages 60%
out: feces 4% sweat 8% insensible losses via skin and lungs 28% urine 60%
What is hydrostatic pressure?
Osmotic pressure?
HP: pressure due to fluid pushing against vessels wall - pushing fluid out of the capillary (in capillary 35 mm Hg at arterial end and 17 mm at venous end)
OP: pressure due to presence of nondiffusable solutes (plasma proteins)
- in capillary: pulling fluid in
What leads to an increase in Na+ concentration in the body? (hypernatremia)
- water loss
- Na+ excess
(normal plasma Na+ = 140-145 mmol/L)
What leads to a decrease in Na+ in the body? (hyponatremia)
- water excess
- Na+ loss
Consequences of hyponatremia and hypernatremia?
- water moves in or out of cells: cells will shrink or swell, this has profound effects on the brain
- neuro function is altered:
rapid shrinking can tear vessels and cause hemorrhage
rapid swelling can cause herniation because skull is origin, brain can’t increase volume more than 10% w/o herniation
Difference b/t hypertonic and hypotonic solution and effect on cells?
- in hypotonic - cell swells because solution isn’t as concentrated, water moves into the cell
- in hypertonic: cell shrinks because solution is so overly concentrated - water moves out of the cell
What does extracellular hypertonicity increase? clinical significance?
- expression of gene encoding proteins that increase intracellular osmoles:
membrane transporters: Na+-H+ exchanger
enzymes: aldose reductase that synthesize intracellular solutes (sorbital)
clinical significance: rapid changes in ECF tonicity alter cell volume and cause neuro complications, while slow changes have much less effect on cell volume and much less clinical effect
Largest percentage of body fluid?
- intracellular fluid: 28 L
Describe how body stays in equilibrium with fluids?
- fluid loss= fluid intake
- electrolyte loss = electrolyte intake
- fluid intake: reg by thirst mech, habits
- elect intake: dietary habity
- fluid output: reg mainly by kidneys
- elect output: reg mainly by kidneys
Function of the glomerulus?
- filtration of blood
- network of capillaries involved in 1st step of urine formation
- receives blood from afferent arteriole and leaves glomerulus by efferent arteriole.
- plasma filtrate flows from glomerulus into bowmans capsule
(glomerulus + bowman’s capsule = renal corpuscle - fxn production of filtrate)
Function of Bowman’s capsule?
- Beginning of nephron, receives filtrate from glomerulus
- plasma filtrate passes through 3 layers:
1) capillary endothelium
2) basement membrane (neg charged) - almost any molecule smaller than 3 nm can pass freely into capsular space.
3) podocytes of Bowman’s capsule - molecules that can be filtered out: water, salt ions, electrolytes, glucose, AAs, and urea, lipids
- larger molecules: proteins, RBCs don’t normally get filtered out (unless kidney infection or trauma - let proteins and RBCs pass through)
Where does most of the active secretion occur?
- distal convoluted tubule: uric acid, K+, H+, drugs, foreign substances, creatine, bile salts
Where does most of the reabsorption occur? difference b/t active and passive transport?
proximal tubule
- active transport: require ATP - Na/K pump, symporter (Na with glucose or AAs), antiproton (Na+ and H+)
- passive transport: Na symporter (glucose, aas), ion channels, osmosis of water (medulla)
What factors affects reabsorption?
- high concentration of solute can exceed the threshold of the kidney’s ability to reabsorb it. (ex: glucose - 180 mg/dl - renal threshold). If above threshold - then it will spill in the urine
- rate of flow: increased rate of flow decreases reabsorption
What is the function of the proximal convoluted tubule?
- very active, infolded plasma membrane - one layer of epithelial cells with long apical microvilli, reabsorbs about 65% of glomerular filtrate
- 75% of Na is reabsorbed here
- TUBULAR REABSORPTION of vital substances is primaray fxn of PCT
- isotonic reabsorption of all organic nutrients (glucose and aas), and most bicarb, Na+ and chloride, and 75-90% of H2O
- generates and secretes ammonia (buffers pH)
- ** angiotensin II acts in proximal tubule to increase Na+ and H2O reabsorption. PTH acts on this to increase phosphate excretion
What drugs work on the PCT?
- acetazolamide and mannitol
2 different categories of nephrons?
- cortical: 85% of nephrons, originate in superficial part of cortex, they have short, thick loops of Henle that penetrate only a short distance into the medulla.
- juxtamedullary nephrons: remaining 15%, originate deeper in corext and have longer and thinner loops of Henle that penetrate the entire lengh of the medulla. These are largely concerned with urine concentration
How many liters of filtration a day do the kidneys produce? O2 consumption?
- 180 L = 47 gallons
178.5 L gets reabsorbed
normal GFR: 120-125 ml/min - O2 consumption: 20-25% of body’s O2
steps of kidney functions?
1: glomerular filration
2: tubular reabsorption removes useful solutes from the filtrate, returns them to the blood
3: tubular secretion removes add wastes from the blood and adds them to the filtrate
4: concentration: removes water from urine, concentrates wastes
Function of the loop of Henle (thin descending limb)
- passively absorbs H2O (perm to H2O) but impermeable to sodium and solutes
Function of thick ascending limb of loop of Henle?
- impermeable to H2O but actively reabsorbs Na+(25%), K+, Cl- via co-transporter
- indirectly aids in reabsorption of Mg+ and Ca+
- TAL helps maintain hyperosmotic medullar gradient needed to produce concentrated urine (in presence of ADH)
What diuretics work on TAL? SE of these diuretics?
- loop diuretics
- unable to concentrate urine - produces very dilute urine
- SEs:
hypocalcemia, hypomagnesemia, and hypokalemia. decreases reabsorbtion of Na+, K+, and Cl- and also indirectly inhibits Mg+ and Ca+ reabsorption. - hypochloremic metabolic alkalosis: since chloride is lost due to reduced absorption, body reabsorbs bicarb to maintain electro neutrality
- hyponatremia: prevent concentration of urine (more common in thiazide diuretics)
Function of Early DCT?
- reabsorbs Na+ (5%)
- TUBULAR secretion is the main job (organic acids, toxins, drugs, K+, H+)
- dilutes urine by actively reabsorbing Na+ and Cl-
- PTH: to increase Ca+ reabsorption (Ca+/Na+ exchange)
What diuretics work on early DCT?
- thiazide diuretics: impair urinary dilution, may cause hyponatremia if increased water intake
Main function of DCTs?
- dermine final osmolarity of urine (via aldosterone and ADH)
adosterone: increases Na+ reabsorption (1-2% of Na) - ADH: concentrates urine, reabsorb water, only permeable to water in presence of ADH (increase in ADH during hypovolemia, hyperosmolarity, and increased RAAS act)
What diuretics work on DCTs?
- K+ sparing diuretics (inhibits aldosterone so can’t exchange K+ for Na+ reabsorption)
- worried about hyperkalemia and metabolic acidosis
Function of the collecting duct?
- variable reabsorption of water and reabsorption or secretion of Na+, K+, H+, and bicarb ions
What is renal clearance?
- of a substance is the vol of plasma completely cleared of a substance per min by the kidneys
What substances are used to measure GFR?
- substances that are freely filtered and not reabsorbed - inulin, I-iothalamate, and creatinine - renal clearance = GFR
Relationship b/t GFR and serum creatinine concentration?
- normal GFR: 125 ml/min = 0.8-1.3
- if it decreases by half - 60: Cr concentration = 2, not good!! - half kidney function
- drops down to 25 ml/min - Ccr = 8 - probably need dialysis, sx
clearance rate =?
- renal plasma flow
- if substance completely cleared from the plasma, its clearance rate is equal to renal plasma flow
What is PAH?
- para-aminohippuric acid
- freely filtered and secreted and is almost completely cleared by the renal plasma
- amt entered = amt secreted
(normally EpAH= 90%)
Net filtration pressure in glomerulus?
- HP of glomerulus = 60 mm HG and colloid osmotic pressure = 32
- Bowman’s capsule pressure = 18
- net filration pressure (60-18-32 = 10 mm Hg)
What is the GFR?
- amt of filtrate formed per minute by 2 kidneys combine
- 99% of filtrate reabsorbed (1-2 L of urine/day is excreted)
Renal autoregulation?
– ability of kidneys to maintain relatively stable GFR in spite of changes (75-175 mmHg) in arterial BP
How does the nephron prevent drastic changes in the GFR when BP rises?
1) constriction of afferent arteriole to reduce blood flow into the glomerulus if BP rises
2) dilation of efferent arteriole to allow blood to flow out more easily
(if BP drops - opposite occurs)
What is myogenic response?
- muscles of arterioles responding to pressure changes (constricting or dilating)
- if decrease in blood flow, increase resistance (constriction) in afferent arteriole so Pg decreases and there will be decrease in GFR
- if decrease in blood flow - increase pressure in Pg by Iincreasing resistance in efferent arterioles so GFR increases
- so increase in Re = increase in GFR
- increase in Ra = decrease in GFR
What is tubuloglomerular feedback?
Since afferent arteriole adjacent to macula densa: easy to adjust to BP
- if Na+ increases, K+ increases BP will result in dilation of afferent arteriole and constriction of efferent - to increase GFR and decrease RBF
What are other factors that influence GFR?
- prostaglandins: increase GFR
- NSAIDs - decrease GFR, especially in volume depleted states
- fever, pyrogens: increase GFR
- glucorticoids: increase GFR
- aging: decrease GFR (10%/decade after 40 years)
- increased dietary protein
- hyperglycemia: increases GFR (DM)
How does Macula Densa feedback work?
- decreased GFR leads to decreased distal NaCl delivery and this leads to decreased NaCl in Macula densa - this leads to decreased afferent arteriolar resistance which in turns increases GFR back to normal (this inhibits the the feedback mechanism)
What percentage of water and other molecules of the filtrate are normall reabsorbed back into plasma by renal tubules?
- 99%
What are the mechanisms of PCT reabsorption?
1) solvent drag
2) active transport of Na
3) secondary active transport of glucose, AAs, and other nutrients
4) secondary water reabsorption via osmosis
5) secondary ion reabsorption via electrostatic attraction
6) endocytosis of large solutes
Describe active transport of Na+
- Na+ pumps (Na-K ATPase) in basolateral membranes transport Na+ out of cells against ints concentration gradient using ATP
Describe secondary active transport of glucose, AAs, and other nutrients?
- various cotransporters can carry both Na+ and other solutes, for ex: SDGT - can carry both Na+ and glucose
Secondary water reabsorption via osmosis?
- Na+ reabsorption makes both intracellular and extracellular fluid hypertonic to the tubular fluid so water follows Na into peritubular capillaries
Secondary ion rabsorption via electrostatic attraction?
- neg ions tend to follow + Na+ ions by electrostatic attraction (Cl-)
Endocytosis of large solutes?
- glomerulus filters a small amt of protein from the blood. The PCT reclaims it by endocytosis, hydrolyzes it to AAs, and releases these to ECF by facilitated diffusion
What substances reach a threshold so they can no longer be reabsorbed - urinated out?
- glucose, AAs, phosphate, and sulphate
What is the transport max?
- limit to the amt of solute that the renal tubule can reabsorb because there are limited numbers of transport proteins in the plasma membranes
- if all transporters are occupied as solute molecules pass through - some solute will remain in tubular fluid and appear in the urine (glucose - DM)
Which limb of loop of Henle is premeable to water?
- thin descending limb is very permeable
- thick ascending: not permeable, but reabsorption of Na, Cl, K, Ca, bicarb, and Mg take place here
What is the purpose of the loop of Henle being permeable and then impermeable to water?
- primary purpose is to esablish a high extracellular osmotic concentration
- the thick ascending limb reabsorbs solutes but is impermeable to water, thus the tubular fluid becomes very diluted while extracellular fluid becomes very concentrated with solutes
- this enables the collecting duct to concentrate the urine later on
What is a distinguishing feature about the distal convoluted tubules?
- this is where the renal tubule is subject to hormonal control
Affect of Aldosterone?
- secreted from adrenal gland in response to decrease in Na+ or increase in K+ in the blood
- to increase Na+ absorption and K+ secretion in the DCT and cortical portion of the collecting duct
- it helps maintain BP and volume
Difference in characteristics of early and late distal tubule and collecting tubule?
- early distal tubule: not perm to H2O but very permeable to urea
- late distal tubule: perm to H2O, depends on ADH
- not very permeable to urea
What cells in the collecting tubules respond to ADH?
principle cells
Angiotensin II affects?
- increases Na+ and water reabsorption by:
stimulating aldosterone, directly increasing Na+ reabsorption (proximal, loop, distal and collecting tubules) - constricts efferent arterioles, decreases peritubular capillary hydrostatic pressure, and increases filtration fraction which increases peritubular colloid osmotic pressure
How do ACEIs and ARBs work?
- decreass aldosterone
- directly inhibit Na+ reabsorption
- decrease efferent arteriolar resistance
- this leads to natriuresis and diuresis and decrease in BP
What is atrial natriuretic factor?
- secreted by atrial myocardium in response to high BP
- it inhibits Na+ and H2O reabsorption, increases the output of both urine, and thus reduces BP and volume
(why ANP is elevated in CHF - trying to get rid of fluid) - increase in ANP leads to increase of GFR, decrease in renin release, and decrease in aldosterone - this all leads to increase of Na+ and H2O excretion
What is tubular secretion?
- renal tubule extracts chemical from the blood and secretes them into tubular fluid. Bile salts, oxalate, urate creatinine, and catecholamines. All are poorly reabsorbed
- this serves purpose of waste removal and acid-base balance
Process of concentrating urine in collecting duct?
- CD begin in the cortex, where it receives tubular fluid from numerous nephrons
- CD reabsorbs water
1. the driving force: high osmolaritiy of ECF generated by NaCL and urea provide driving force of water reabsoprtion
2. regulation: the medullary portion of the CD isn’t permeable to water (depending on ADH)
What does control of urine concentration depend on?
- body’s state of hydration
- in a state of full hydration: ADH is not secreted and CD permeability to water is low, leaving water to be excreted
- in state of dehydration, ADH is secreted, the CD perm to water increases and with increased reabsorption of water by osmosis, the urine becomes more concentrated
Where is ADH synthesized?
- in magnocellular neurons of hypothalamus, released by posterior pituitary, and action is taken by the kidneys
What diseases affecting the kidney are systemic disorder that are not limited to the organ itself?
- systemic vasculitides
- autoimmune diseases (lupus)
- congenital or genetic conditions such as polycystic kidney disease
3 most common causes of chronic kidney disease?
- DM
- HTN
- glomerulonephritis
When is renal disease classified as end stage?
- when the GFR is less than 15
Glomerulopathies?
- diseases that affect the glomeruli or nephron: can be inflammatory or non-inflammatory:
nephritic syndrome
IgA nephropathy
nephrotic syndrome
What is hemodialysis?
- pts blood is pumped throuh dialyzer that has partially permeable membrane composed of thousands of tiny hollow fibers. Blood flows through the fibers and dialysis soln flows around outside of fibers, and water and waste are removed. The cleansed blood is returned back to the pt
What is peritoneal dialysis?
- sterile soln dialysate runs through tube into peritoneal cavity, where the peritoneal membrane acts as the partially permeable membrane
- diffusion and osmosis drive waste products and excess fluid through the peritoneum into the dialysate soln until the solution approaches equilibrium with the body’s fluids
- then the soln is drained and replaced with fresh dialysate
- this is repeated 4-5x a day
- this helps free the pt from going to dialysis 3-4x a week
