PRIN 10 Body Fluids Flashcards
Normal Body Water
Male vs Female
MALES: 60%
FEMALES: 50%
difference due to fat
NOTE: depends on physique and age
Normal Body Water
What is the affect of aging?
Newborn vs Elderly?
we gradually lose water percentage as we age
“newborns are more water and less substance
elderly are less water and more substance”
Newborns are 80% water!
Which organs have the highest percentage of water?
top 3
All have 80% water
(1) Kidney
(2) Heart
(3) Lung
Compartments of Body and Difference in Water Composition
TOTAL BODY WATER = 60%
40% ICF
20% ECF
5% plasma, 15% ISF
What is ISF?
Interstitial Fluid =
Fluid (water) outside of cells: includes Lymphatics and Transcellular Fluid
What is Transcellular Fluid?
CSF, synovial fluid, pericardial fluid, pleural fluid etc …
WE IGNORE IT (so small … unless pathology)
What is ICF?
Intracellular Fluid
- fluid inside cells
- all cells including blood cells
Which organs have the lowest percentage of water?
Skeleton (20%) Adipose Tissue (10%)
How can measurements of the various fluid compartments be done?
Indicator Dilution Method
TBW: D20 & Antiypyrine
ECF: Inulin & Na+*
Plasma Vol: Albumin* or Evans blue dye
Composition of ICF`
Cations & Anions …?
plasma water, proteins, lipids
Cation: K+
Attendant Anions: proteins, organic phosphates, acids
Composition of Plasma
Cations & Anions …?
Cation: Na+
Attendant Anions: Cl- & HCO3-
Equation for calculating Blood Vol
BV = Plasma Volume / 1-hematocrit
Which is the correct term to use?
Osmolarity or Osmolality?
Osmolality
since the volume of water can be affected by
changes in temperature
What is the eq/mol of Ca2+
2
two charges
What is the osmol/mol of Ca2+
1
only 1 species
What is the eq/mol of CaCl2?
4
four charges
What is the osmol/mol of CaCl2?
3
three species when dissociated
Formula for Osmotic Pressure:
van’t Hoff’s Law
Osmotic Pressure = nRTCk
C = [total solute] expressed in osmoles; the # of dissociated particles
k=osmotic constant
What is Plasma Water?
the volume of plasma that is associated only with the water and not the dissolved solutes
[Plasma Water] = [Plasma] / 0.93
Composition of ISF
Cations & Anions …?
Similar to Plasma, but hardly any proteins
Cation: Na+
Attendant Anions: proteins, organic phosphates, acids
What is the normal Osmolality of Body Fluids?
280 to 300 mosmol/kg water
Hyperosmotic >300
Hypo-osmotic <300
What IS Osmolality?
total number of osmotically active particles (all solutes) dissolved in water (solvent)
What are the major sources of water input?
MOST to LEAST
Drinking
Food
Oxidation of Food
What are the major sources of water output?
MOST to LEAST
Urine
Insensible Loss
Sweat
Feces
What are Starling’s Forces?
forces that determine the direction of fluid exchange across a membrane
Pc - cap. hydrostatic pressure
Pi - interstitial hydrostatic pressure
πc - capillary oncotic (colloidal osmotic) pressure; mainly exerted by proteins
πi - interstitial oncotic pressure (usually very small)
What is Oncotic Pressure?
“colloid osmotic pressure”
form of osmotic pressure exerted by proteins in a blood vessel’s plasma (blood/liquid)
pulls water into the circulatory system
opposite to hydrostatic pressure
What is the formula for Starling’s Forces?
Jv = ?
Jv = Kf x (Pc - P i- πc + πi)
What does the value of Jv indicate?
A POSITIVE Jv value indicates that water is forced out of the capillaries and into the ISF
Three Functions of Kidney
(1) Regulatory
(2) Endocrine
(3) Excretion
Three Functions of Kidney
(1) Regulatory … How?
(i) Ionic Composition
(ii) pH
(iii) Body Fluid Vol.
(iv) Long term regulation of BP
How do we calculate BP?
BP = CO x TPR
CO = cardiac output TPR = total peripheral resis.
Three Functions of Kidney
(2) Endocrine … How?
(i) Erythropoietin
(ii) Activation of Vit D
(iii) Production & Release of Vasoactive substances (RAS, kinins, prostaglandins)
What is RAS?
Renin-Angiotensin System:
**Angiotensinogen converted by RENIN (gen in kidney) to ... **Angiotensin I (AI) converted by ACE (gen in lungs) to **Angiotensin II (AII) (potent vasoconstrictor)
What will high blood pressure medications target?
act to block ACE
prevents conversion of AI to AII
(Angiotensin Converting Enzyme)
What are kinins & prostaglandins?
Vasoactive substances produced & secreted by kidney
VASODILATORS
Three Functions of Kidney
(3) Excretion … How?
(i) Formation of Urine
(Micturition)
(ii) Elimination of Waste Products
(urea, uric acid, creatinine)
What does the Renal Corpuscle consist of?
Renal Corp = Bowman’s Capsule + Glomerulus
Short vs Long Loop Nephrons
What are the names?
**Cortical Nephron
(short loop - does not penetrate inner medulla)
(no Asc. Thin Limb)
**Juxtamedullary Nephron
(long loop - penetrates the inner medulla)
(has an Asc thin limb)
Regions of Nephron
PCT: Prox Convoluted Tubule
PST: Prox Straight Tubule
DTL: Desc Thin Limb
ATL: Asc. Thin Limb *(juxtamedullary nephron only)
TAL: Thick Ascending Limb
DCT: Distal Convoluted Tubule
CNT: Connecting Duct
CCD: Corticol Collecting Duct
MCD: Medullary Collecting Duct
OMCD: Outer Medullary CD
IMCD: Inner Medullary CD
What is GFR?
Glomerular Filtration Rate
*the volume of blood being filtered per unit of time (ml/min)
From external to internal of the glomerular capillaries, what are the membrane structures?
Podocytes
Pedicles
Fenestra - windows/pores
What substances pass freely through the glomerular membrane?
Radii of less than 15A
MW neutral>anions
(positive ions travel through easier because the membrane is negatively charged due to proteins)
By what methods can Clearance Values be attained?
Renal Plasma Flow
*clearance of Para-amino-hippuric acid
Glomerular Filtration Rate
Clearance of inulin
How is Clearance calculated?
Cx = UxV / Px
C = Clearance (ml/min) Ux = Urinary [X] (mg/ml) Px = Plasma [X] (mg/ml) V = urinary flow rate (ml/min) UxV = urinary excretory rate of X (mg/min)
Methods for Estimation of GFR
(1) Clearance of Inulin or Creatine
(2) Serum / Plasma Creatinine Conc.
(3) Cockcroft-Gault Formula
(4) Starling Forces
Mechanisms involved in the maintenance of GFR
(1) Myogenic
via smooth muscle
Blood Flow = Change in Pressure / Change in Resistance
(2) Tubuloglomerular Feedback (TGF)
via Juxtaglomerular App.
What is the JGA composed of?
Juxtaglomerular Apparatus
1) macula densa cells
(2) Granular cells (renin producing
(3) extraglomerular mesangial cells (Lacis Cells)
What happens in response to increase in GFR?
Macula densa cells sense an increase in Na and send out a signal via adenosine & ATP
What happens in response to decrease in GFR?
Macula densa cells sense a decrease in Na
send out a signal via NO, prostaglandins, and LESS purines (adenosine & ATP)
How much Na is actually excreted?
Less than 1%. It is essentially all reabsorbed
Where is the nephron impermeable to Na?
Descending Thin Limb
What hormones are involved in the re-absorption of Na?
Where do they act?
ANGIOTENSIN II, NE, E
Proximal Tubule
ALDOSTERONE
*Distal Tubule
What is Fractional Excretion?
Formula?
the fraction of filtered load that is being excreted by the kidney
FE = (UV)/(PxGFR)
What is Fracitonal Reabsorption?
1-FE
Where does water reabsorption occur?
PT - 66%
small amounts are absorbed elsewhere
BUT, water is NOT absorbed in ATL & TAL
Na & Water
Where does each one NOT get reabsoribed?
Na+ does not get reabsorbed in the DTL
Water does not get reabsorbed in the ATL or TAL
What is AVP?
Arginine vasopressin
aka “ADH” for its function as an antidiuretic
Where does AVP act?
late DT and CT
upregulates AQP-2 (apical
aquaporins)
Where do specific aquaporins act?
AQP-1 acts on:
Proximal Straight Tubule (PST)
Desc. Thin Limb (DTL)
AQP-2(apical), 3 & 4(basal) act on the CCD & CD
Where is the control center for ADH synthesis?
Paraventricular Nucleus
Supraoptic Nucleus
Where does ADH synthesis actually occur?
Where is secreted from?
ADH synthesis in Magnocellular neurons / Magnocellular Neurosecretory Cells
Secreted from Neurohypophysis Nerves (post. pituitary)
How is ADH made?
Pre-pro-vasopressin gets cleave into sections:
Vasopressin
Neurophysin II (binding protein)
What are possible explanations for the faulty vasopressin?
(1) defective vasopressin, OR
(2) defective Neurophysin II
When do osmoreceptors become activated?
Normal = 280-300
AVP is ALWAYS secreted to some degree
Above 300, AVP enhanced secretion
Below 280, AVP not enhanced
Osmotic Threshold for Thirst >289
Where are osmoreceptors located?
(1) organum vasculosum lamina terminalis (OVLT)
(2) subfornical organ (SFO)
(3) median preoptic nucleus (MnPO)
(4) supraoptic nucleus (SON)
What do baro-receptors do?
Sense stretch changes:
HIGH PRESSURE:
(1) aoritic arch
(2) carotid sinus
(3) JGA
LOW PRESSURES:
(1) atria
(2) veins
What happens when decreased volume is detected?
Na+ Re-absorption Increased by neural & hormonal means
ANGIOTENSIN II, NE, E
Proximal Tubule
ALDOSTERONE
*Distal Tubule
What happens when increased volume is detected?
Na+ Re-absorption Decreased by neural & hormonal means
Atrial Natri-uretic Peptide
-inhibits Aldosterone & AVP secretion (thereby inhibiting Na+ reabsorption)
What is hyponatremia?
low Na+
What is Polydypsia?
excessive thirst
What is Polyuria?
excessive urination
What is Nocturia?
getting up in night to pee
Hypernatremia?
Hypercapnia?
Hyperkalemia?
Hypercalcemia?
natremia = Na+
capnia = CO2
kalemia = K+
calcemia = Ca2+
ECF vs ICF
What can we measure?
We can only manipulate the ECF clinically and only measure changes in the ECF.
We can only infer changes in the ICF.
What is the main role of Angiotensin 2?
(1) Vasoconstriction
(2) Sodium Handling via Aldosterone
(3) Stimulate Post Pit to release ADH & Stimulate Thirst
What happens to GFR when we constrict the Afferent arteriole?
Reduces GFR
What happens to GFR when we constrict the Efferent arteriole?
Raises GFR
What is the effect of Angiotensin II on GFR?
AngII blocks the efferent more than afferent
Therefore, GFR goes up
What is the effect of Angiotensin II inhibitor?
Decreases Efferent Constriction
GFR goes down
How to diagnose DI?
Diabetes Inspidus
24 hr Water Restriction Test
What are the four types of DI?
(1) Primary polydipsia (psychogenic)
(2) Central/Neurogenic
(3) Nephrogenic
(4) Gestational
Central DI
Response to Water Restriction Test
After water restriction:
VERY dilute urine
After water restriction and treatment with Desmospressin:
Normal, concentrated urine
Nephrogenic DI
Response to Water Restriction Test
After water restriction:
VERY dilute urine
After water restriction and treatment with Desmospressin:
VERY dilute urine … no change
What causes Central DI?
Post. Pit does not produce AVP (ADH) due to genetic mutation in the Nerophysin portion or trauma
Therefore, these patients respond to DDAVP (desmospressin)
What causes Nephrogenic DI?
Mutation gives to rise to faulty AQP gene. Normal ADH but nephron doesn’t respond to it.
Therefore, insensitive to DDAVP
How can pregnancy result in Gestational DI?
Placenta releases enzyme that degrades AVP.
General Causes of DI:
Injury / Trauma
Disease/Drugs
Genetic
Idiopathic (aka … nobody knows!)
What does a bright spot on the Post. Pit indicate during an MRI?
Function, ADH secreting neurons
What are the nuclei in the brain involved in AVP secretion?
SON: Supraoptic
PVN: Paraventricular
Which kidney is lower?
Right, due to presence of liver
Osomoreceptors vs Baroreceptors
Sensivity
Osmoreceptors sense change within 1-2% (very sens
Baroreceptors sense change within 10%
What is ANP?
Antri Natri-uretic Peptide
Released from myocytes of the Cardia Atria
Causes vasodilation
(would get inhibited in the presence of decreased circulating volume)
What is TGF?
Tubuloglomerular feedback
main job is to prevent severe loss of Na+
causes constriction of afferent artery in the presence of volume depletion
What stimulates release of ADH?
Physiological factors:
osmolality, pain, nausea, fear, anxiety
Non-physiological factors:
drugs, cancer, chronic lung disease, intracranial bleeding
How do glucose and Na+ interact?
fo revery 10 mmol increase in glucose, approx 3 mmol drop in Na
What is dyspnea?
SOB
What does JVP reveal?
Jugular Vein Pressure
when high and distended suggests high ECF volume
How does Congestive Heart Failure affect the kidney?
Blood backs up, resulting in low BP. Therefore, the kidney responds by retaining sodium and water in order to raise BP back up.
What is the effect of an ACE inhibitor?
Causes BP to decrease
What abnormalities can lead to disease state of DI?
(1) deficiency in AVP production
(2) defect of the aquaporin II gene
(3) defect of the thirst center
(4) increased metabolic clearance of AVP
The sensors for detecting changes in extracellular fluid volume (ECFV) and osmolality, respectively are…
Volume receptor
Osmoreceptor
What happens when we eat lots of salt
Plasma Na increases
Osmoreceptors in the brain detect increased Na+ (organum vasculosum of the lamina terminalis (OVLT))
Triggers thirst & ADH secretion
What are the values of U-osm at Max and Min ADH
1200 mosmol/kg H20 at max ADH
70 mosmol/kg H20 at min ADH.
What are glucose levels like in DI and DM?
DI: normal glucose levels
DM: elevated glucose levels
Where is renin produced?
granular (juxtaglomerular) cells of the afferent arterioles in the kidney
What are the units to express osmolalitity?
mmol/kg
What is the major cation and anion in ISF?
Na+
Cl-
To replenish a decreased ECF volume containing an abnormally high sodium, you would choose
Hypertonic glucose solution
(Glucose is subsequently metabolized and leaving the water behind to dilute the high osmolality generated by the high [sodium]).
Where are Osmoreceptors located?
organum vasculosum of the lamina terminalis (OVLT)
and the subfornical organ
Renin secretion is elicited by:
Decrease in glomerular filtration rate
What happens when GFR decreases?
Renin is secreted from the granular (juxtaglomerular) cells of the afferent arterioles in the kidney
What is the role of Aldosterone?
Increase reabsorption of Na in the late DT and CD.
What does a Negative C_H20 number mean?
If the value of C_H20 is negative that means water is being reabsorbed.
(positive for excretion)
If the efferent arterioles in the glomeruli of the kidneys are constricted.
How effect renal plasma flow?
How affect GFR?
Renal Plasma Flow decrease
GFR will decrease