Chapter 25
Body water 60% of body weight, less in women
cuz more fats
With prolonged heavy exercise, urine output
decreases but sweat increases
Intracellular fluid is 40% - 28L
Extracellular is 20% - 14L
Interstitial fluid 11L
Plasma 3L - higher protein concentration
Blood is 5L - 2L RBC
Osmotic pressure (pi)- amount of pressure
preventing osmosis from a semipermeable
membrane;
pi = CRT (C - solutes concentration, R - gas constant, T absolute temperature in K)
Isotonic = having the same osmotic pressure
19.3 mmHg force per 1mOsm/L solution
Isotonic solution - 0.9% saline, 5%
dextrose
Isotonic solution - same osmolarity as a cell
Hypertonic - more osmotic substances than
the cell
Intracellular swelling - hyponatremia, lack of nutrition → Na ions stay in the cell → water influx
Acute - cell water increases
Chronic - cel ions decrease
Hypernatraemia - dehydration or no ADH (diabetes insipidus)
Extracellular edema - leakage of fluids to the interstitial space and lymphedema (lymphatics do
not bring fluid to blood)
Kf is the capillary filtration coefficient (the product of the permeability and surface area of the
capillaries), Pif is the interstitial fluid hydrostatic pressure, pc is the capillary plasma colloid
osmotic pressure
Too increased filtration → edema
In heart failure capillary pressure is increased, reduced blood flow triggers RAAS and water
retention
Safety factors:
Low tissue compliance (3 mmHg) if Pif is negative, if interstitial V ↑ → Pif increases
Lymph flow can increase (7mmHg) which decreases protein concentration and lowers net
filtration force, washdown of interstitial fluid concentration (7 mmHg)
● Most fluid in the interstitium is in gel form in a proteoglycan mesh and it has negative
pressure. When P becomes positive, there is free fluid - pitting edema
Combined - 17mmHg safety factor
Chapter 26
Excretion = Filtration – Reabsorption + Secretion
Vasa recta - peritubular capillaries supply the renal
medulla
Micturition - the urinary bladder empties
Ureters - renal pelvis to bladder, pushed by parasympathetically elicited peristaltic contractions
Detrusor bladder muscle
Sacral plexus - pelvic nerves
(Six
Ps
●
●
●
●
●
●
nerve to piriformis (S1-S2)
perforating cutaneous nerve (S2-S3)
posterior femoral cutaneous nerve (S1-S3)
parasympathetic pelvic splanchnic nerves (S2-S4)
pudendal nerve (S2-S4)
perineal branch of S4 (S4)
SLIP, DSP
●
●
●
●
●
●
●
S: superior gluteal nerve
L: lumbosacral trunk
I: inferior gluteal nerve
P: posterior femoral cutaneous nerve
D: direct branches to lateral rotators (including nerve to piriformis, nerve to obturator internus,
nerve to quadratus femoris, etc), and pelvic floor
S: sciatic nerve
P: pudendal nerve)
Pudendal nerve can inhibit the external sphincter and cause urination
Filtration fraction (renal blood flow that is filtered) = 0.2
Filtration fraction = GFR/Renal Plasma Bloodflow
Pg - hydrostatic inside capillaries = 60mmHg
Pb - opposes filtration = 18
Pig - colloid pressure inside capillaries, opposes filtration = 32
Pib - around zero, no effect
Urine stones ↑Pb
↑arterial colloid pressure or ↑filtration fraction (that concentrates the plasma proteins) →↓GFR
Glomerular capillary hydrostatic pressure (Pg) is controlled by arterial pressure, afferent
arteriole resistance (decreases it) and efferent arteriole resistance (increases it)
Control:
SNS decreases GFR (constricts arterioles)
Epireprine too
Endothelin constricts arterioles
Angiotensin II constricts efferent arterioles ♥ →↑GFR
Increases Na+ reabsorption in the proximal tubule (aldosterone does it in the distal)
Prostaglandins prevent the afferent arterioles from being constricted
ANP is opposite to RAAS, it decreases sodium reabsorption, it is released upon cardiac
stretch
ENDO ↑GFR
Prostaglandins might dampen angiotensin response on afferent arterioles (aspirin blocks them
→ ↓GFR)
Prerenal - decreased pressure in glomerular capillaries
Renal - filtration is affected
Postrenal - increased pressure in Bowman's -- pressure build up
Tubuloglomerular feedback - ↓BP→↓Na →↓afferent arterioles resistance which ↑Pb and ↑renin
Myogenic response - how arteries react to increase or decrease in blood pressure, when
smooth muscle cells are stretched, they contract to resist the pressure. Autoregulation
Dilation of afferent arterioles increases GFR
Decreased GFR increases reabsorption in proximal → less Na+ for distal → macula densa raises
piG
↑protein ↑GFR cuz ↑amino acids reabsorption and ↑NACl proximal reabsorption → ↓Cl to
macula densa and ↓afferent arterioles resistance
Renin is stored in juxtaglomerular cells in the afferent arterioles
Chapter 27
Reabsorption:
Transcellular route - through membranes
Paracellular route - junctional spaces between cells
Ultrafiltration → bulk flow through peritubular capillaries (large reabsorptive force, moving from
interstitium to blood)
Na-K pump on basolateral membrane brings Na to interstitium and K in the cells
K rich foods - bananas, oranges, spinach, potatoes, peas, zucchini, avocado, oatmeal
Secondary active glucose and AA reabsorption
Na diffuses through electrochem gradient, the energy is used to push glucose
Transport maximum - max rate of reabsorption
ADH determines water reabsorption in distal tubules and ducts
Descending loop of henle makes fluid hyperosmotic
Ascending loop is impermeable to water but reabsorbs solutes
Early distal tubule - diluting segment - 100mOsm/L osmolarity
Late distal tubules and cortical collecting tubules:
Principal cells (aldosterone acts on them) - potassium sparing happens, K leaves the
cell, sodium is reabsorbed
Type A intercalated cells, they eliminate H+ and reabsorbs bicarbonate, reabsorb K as
well. this is important in acidosis
Type B intercalated cells - secrete bicarbonate, important in alkalosis
Aldosterone controls Na reabsorption in the distal convoluted tubules
Made in the adrenal gland, angiotensinII stimulates aldosterone release
Medullary collecting ducts determine final urine output
Permeable to urea with transporters →raises osmolarity
Secretes H ions
No aldosterone →Addison’s → Na loss
Conn’s → too much Na → K depletion
Angiotensin II:
- Stimulates aldosterone secretion
-
Constricts efferent arterioles which ↑filtration fraction due to ↓renal blood flow
→↑reabsorption
-
Directly stimulates Na
Reabsorption
Reduces medullary blood flow through vasa recta
Atrial Natriuretic peptide ↓Na reabsorption, opposes RAAS
Parathyroid hormone ↑Ca reabsorption
Renal clearance CX is renal clearance in milliliters per minute,
UX V is the excretion rate of substance X (UX is the
concentration of X in the urine, and V is urine flow rate
in milliliters per minute), and PX is the plasma concentration of X.
Creatinine clearance = GFR
Rate of filtration = GFR* Plasma concentration
Rate of excretion = Ux* Urine volume
Chapter 28
ADH makes it permeable to water so water can be reabsorbed, this decreases urine volume
but does not alter solute excretion
Dilute urine - ↓ADH
Concentrated urine: ↑ADH and ↑osmolarity of renal medulla
Secreted from pituitary gland, also called vasopressin
Countercurrent multiplier - using energy to generate an osmotic gradient that enables water
reabsorption
Build up of solute concentration in the renal medulla due to:
- Active transport from ascending Henle limb
- Active transport from collecting ducts
- Diffusion of urea
- Less water diffusion
Vasa recta preserves hyperosmolarity of renal medulla - minimizes solute loss because it
flows slowly
Osmolar clearance - the rate of which solutes are cleared from the blood - Cosm
, V is urine flow rate
Free water clearance - difference between water excretion (urine flow rate) and osmolar
clearance C(h20) = V-Cosm
Disorders of concentration ability:
Central diabetes insipidus - ↓ADH secretion
Nephrogenic diabetes insipidus - kidneys do not respond to ADH
Osmoreceptor-ADH Feedback system
- Osmoreceptor cells in hypothalamus stimulate pituitary, ADH is released and the solutes
are diluted
Cardiovascular reflex stimulation - upon reduced BP or volume (ADH is not very sensitive to
blood volume loss)
Thirst - due to increased extracellular fluid osmolarity and decreased volume, as well as
angiotensin II
Aldosterone and Angiotensin II control Na excretion, not Na plasma concentration because
- They increase water reabsorption
- Thirst and water intake compensate for Na concentration
Renal Regulation of Potassium, Calcium,
Phosphate, and Magnesium; Integration
of Renal Mechanisms for Control
of Blood Volume and Extracellular
Fluid Volume - 223-235
Chapter 29
Potassium - 4.2mEq/L in ECF, most rapidly moves into the cells with the help of insulin and
aldosterone, also during alkalosis, exercise releases K from skeletal muscle
Mostly regulated by secretion in distal and collecting tubules in the principal cells by:
1. Passive diffusion from blood to interstitium
2. Na-K pump into cells
3. From cell interior to tubular fluid
Factors:
↑K concentration increases secretion
↑aldosterone→↑secretion
↑flow rate→↑secretion
Type A intercalated cells can absorb it and type B can secrete it
Alkalosis increases secretion
Calcium - in bones
Parathyroid hormone ↑reabsorption of bone salts, activates vitamin D (that stimulates intestinal
Ca+ absorption)
PTH reduces excretion, greater phosphate plasma concentration stimulates that
Stimulated by acidosis
Extracellular fluid - dependent on NaCl
Excretion = Glomerular filtration - tubular reabsorption
Intrarenal buffering mechanisms:
1. Glomerulotubular balance - ↑reabsorption if ↑GFR (the ability of the nephron to
reabsorb)
2. Macula densa feedback - ↑NaCl delivery causes afferent arteriole constriction →↓GFR
Pressure Natriuresis
Pressure diuretics - ↑arterial pressure→↑water excretion
Loss of fluid from plasma to interstitial space (edema) due to ↑capillary pressure, ↓plasma
colloid pressure, ↑ capillary permeability
↑SNS activity reduces Na and water excretion due to renal vasoconstriction, increased
reabsorption and ↑renin which helps reabsorption
ADH guides and increases water reabsorption
A lot of Na intake →
Inhibited SNS activity increases secretion
↑Atrial natriuretic peptide that decreases reabsorption
Suppressed formation of angiotensin II
↑in arterial pressure → pressure natriuretics
Increased ECF and blood volume:
Heart failure - low pressure, kidneys retain fluid → pulmonary edema
Pregnancy increases vascular capacity, varicose veins too → ↑blood volume
Increased ECF but normal blood volume:
Nephrotic syndrome - loss of plasma protein reduces plasma colloid osmotic pressure → edema
cuz capillaries filter larger volumes that decrease plasma volume
Liver cirrhosis - decreased plasma protein synthesis
Kidney lecture notes:
Fraction of filtrate reabsorbed by kidneys - 99%
Glomerular filtration -Autoregulation - despite local increase in blood pressure, the GFR remains the same.
Happens in the afferent arterioles - The myogenic mechanism is how arteries and arterioles
react to an increase or decrease of blood pressure to keep the blood flow within the blood
vessel constant.
Tubuloglomerular feedback is an adaptive mechanism that links the rate of glomerular
filtration to the concentration of salt in the tubule fluid at the macula densa. A high
[NaCl] ---- keeps the GFR constant
Glomerulotubular balance (GTB) is defined as the ability of each successive segment of
the proximal tubule to reabsorb a constant fraction of glomerular filtrate and solutes
delivered to it.
-- difference?
PRA = plasma renin activity
Volume regulation is the first reaction if the drink is isotonic and not pure water
The effect of RAAS decreases if Na+ uptake increases
Thiazide diuretics lead to hypokalemia
Insulin deficiency leads to hyperkalemia
Hyponatraemia x
Cockcroft-Gault Calculator performs best for estimating kidney function
Lecture physiology
1 mol NaCL = 58.5g → calculate a gram
Volume is not determined by filtration but by Na+ reabsorption