What is normal ECF osmolality? Na?
Na = 140 mEq/L
Osm = 285 mOsm/kg
What is normal ICF osmolality? K?
K = 140 mEq/L
Osm = 285 mOsm/kg
What is the equation for plasma osmolality?
2Na + glucose/18 + BUN/2.8
Water balance (pictures)
How is total body water regulated?
- The kidneys
What are the functions of angiotensin II?
1. Stimulates production of aldosterone
2. Acts directly on arterioles to cause vasoconstriction
3. Stimulates Na+/H+ exchange in the proximal tubule
4. Stimulates thirst center
What are the functions of aldosterone?
1. Stimulates reabsorption of Na+ and excretion of K+ in the late distal tubule and collecting tubule.
2. Stimulates activity of H+ ATPase pumps in the late distal tubule and collecting tubule.
- Increases the water permeability of the collecting tubule
- Mildly increases vascular resistance
Where is ADH made? How is release regulated?
- Synthesized in the hypothalamus and stored in the posterior pituitary
- Released in response to plasma hyperosmolality and decreased effective circulating volume
What is the driving force for glomerular filtration rate (GFR)?
What drugs affect GFR?
Drugs that regulate RBF
- Xanthines (caffeine, theophylline, aminophylline) increase CO and vasodilation, resulting in increased RBF
T/F: Filtration is a nonselective process
What determines filtration (factors)?
- GBM permeability
- Net filtration pressure across the capillaries
What types of substances undergo filtration? What remains in the blood?
- All small molecules (electrolytes, AAs, glucose, drugs and metabolic waste) undergo filtration
- Cells and large molecules (lipids and proteins) remain in the blood
How many L get filtered per day? What are the main ions?
- 180 L/day filtered
- Mostly Na, Cl and bicarbonate ions
What is normal GFR?
More than __ of filtered water and electrolytes are reabsorbed
More than 99% of filtered water and electrolytes are reabsorbed
T/F: water is actively reabsorbed to prevent excessive loss following filtration
- Water follows passively (facilitated by water channels AQPs) along the osmotic gradient created by solute reuptake
T/F: Many solutes undergo active transport to be reabsorbed
- AA, glucose, phosphate, electrolytes... etc
What are the two main kinds of "pumps" used in active tubular secretion?
- For organic acids (uric acid, p-aminohippuric acid, diuretics, antibiotics, etc…)
- For organic bases (creatinine, procainamide, choline, etc…)
Where does the process of active tubular secretion mainly take place?
What are the main ion handling functions of the proximal tubule?
- 60% of total NaCl and water reabsorbtion
- 85% of total NaHCO3 reabsorption occurs in the early PT (dependent upon carbonic anhydrase)
- Organic acid/base secretion
There are competitive interactions between diuretics and what?
Uric acid (probenecid) and other organic compounds (may impact diuretic action)
What happens in the tDL?
- Does NOT participate in salt reabsorption
- Passive flux of water through AQP1 (driven by high medullary osmolality)
What happens in the TAL?
Dilution and concentration segment
- Responsible for 25% of NaCl reabsorption
- Impermeable to water
- NaCl transport system: Na.K.2Cl cotransporter (the target of loop diuretics)
- Major site of Mg and Ca reabsorption
Solute removal without water uptake results in urine dilution
NaCl uptake increases the medullary interstitial osmolality and contributes to the concentrating mechanism
What happens in the DCT?
- Water impermeable
- Responsible for 5-10% NaCl re-absorption
- NaCl transporter is blocked by thiazide diuretics
- Aldosterone exerts a significant influence on NaCl co-transporter
- Ca is actively reabsorbed (this process is regulated by parathyroid hormone)
What happens in the collecting duct?
- Responsible for 2-5% of Na re-absorption
- Na transport is mediated by Na channels in principal cells (stimulated by aldosterone)
- Major site of potassium (K+) secretion (negatively charged lumen)
- ADH increases water permeability in collecting tubule, through its action on AQP2, causing concentrated urine (ADH determines final urine concentration)
Na and H2O transporters along nephron (picture)
What may cause fluid deficiency (main causes)? Fluid excess?
- Volume depletion (hypovolemia)
- Volume excess
- Hypotonic hydration
What may cause volume depletion?
Renal losses: diuretics
Skin or Respiratory losses: burns
- Intestinal obstruction
What history might a pt present with in the cause of volume depletion?
Thirst, easy fatiguability, muscle cramps, postural dizziness.
More severe fluid loss can lead to
- chest pain, (coronary ischemia)
- abdominal pain (mesentric )
- lethargy and confusion (cerebral vascular beds)
Clinical signs of volume depletion?
- Dry skin including axilla
- Decreased skin turgor
- Dry mucus membranes
- Thready pulse, low arterial blood pressure
- Orthostatic hypotension
- Decreased jugular venous distension
Lab abnormalities seen with volume depletion?
- Elevated BUN/CR ratio
- Decreased urine
- FeNa – Fractional excretion of sodium.
Therapy for volume depletion?
- Normal saline- 0.9% NaCl
What is seen in volume overload state
Edema- palpable swelling produced by expansion of the interstitial fluid volume
- Dependent bilateral edema
- Localized edema
What is the pathophysiology of edema?
- An alteration in capillary hemodynamics that favors the movement of fluid from the vascular space into the interstitium.
- The retention of sodium and water by the kidneys.
The exchange of fluid between the plasma and the interstitium is determined by what?
Hydraulic and oncotic pressures.
Net filtration = LpS x (Δ hydraulic pressure - Δ oncotic pressure) = LpS x [(Pcap - Pif) - s(nx cap - nif)]
What factors cause edema/volume overload?
1. Increased venous pressure
- Blood volume expansion (heart failure, renal disease)
- Venous obstruction (hepatic cirrhosis, deep venous thrombosis)
- Loss of albumin in urine (nephrotic syndrome)
- Decreased hepatic albumin synthesis (hepatic cirrhosis)
3. Increased capillary permeability
- Malnutrition syndrome
- Idiopathic capillary leak syndrome
4. Lymphatic obstruction (lymphedema)
- Primary: genetic defect
- Secondary: radiation, parasites
5. Renal sodium retention
- Inability to excrete the Na and water (pts with kidney disease)
- Appropriate compensatory response to effective circulating volume depletion, with urine Na under 20 meq/L
Clinical manifestations of edematous states?
- Jugular vein distention
- Pulmonary edema
- Pleural effusions &/or pericardial effusions
- Edema of the lower extremities (> 3L)
- Puffy eyes
- Dyspnea (pulmonary congestion): PND, DOE, Orthopnea
Describe edema in heart failure: pathogenesis, effect on ions...
Perception of low effective arterial blood volume (EABV) due to heart failure
- Activation of sympathetic nervous system,
Renin-AII- Aldosterone and ADH.
Na and water retention by the kidney
- Urine studies
- Low FENa, High SG
Describe the problem with systolic heart failure.
Problem = Low EF
- Treat underlying causes
- Na & water restriction
---- loop diuretics
---- Combination of loop diuretic and thiazide
---- Aldosterone antagonists
- ACEi/Angiotensin II receptor blocker
- Beta blockers
- Vasodilator: Isosorbide and hydralazine
Describe the problem with diastolic heart failure.
Problem = Inadequate LV filling (normal EF)
- Treat underlying causes
- Control of HTN
- Control of ventricular rate in patients with tachycardia
- Control of edema with salt and water restriction and diuretics
Describe the problem with cirrhosis: what is sensed? Ion handling?
- Perception of low EABV due to perpetual arteriolar vasodilatation (?NO, ?PGs).
- As in CHF, sympathetic nervous system, Renin-AII-Aldosterone and ADH are activated.
- Na & water retention follow (low FENA)
- Hepatic flow obstruction favors the formation of ascites
Treatment for edema in cirrhosis?
- Treat underlying causes of hepatic cirrhosis: ETOH, hepatitis
- Na restriction, water restriction if SNa
What is the problem with nephrotic syndrome (NS)?
(Nephrotic syndrome: problem with glomerulus so that pt is losing protein...)
- Activation of the intra-renal renin/angiotensin system, with resultant Na & water retention.
- The cause for activation of the renal AII-system is unknown.
- Except in some children with nephrotic syndrome, the EABV is normal in spite of low serum albumin.
Treatment in NS (nephrotic syndrome)?
- Treat the primary renal disease.
- Na and water restriction.
- High dose loop diuretic.
- Combination of diuretics.
- ACE inhibition is useful (reduce glomerular perfusion and thus proteinuria)
What is the problem causing edema in renal failure and/or GN?
Problem = decreased GFR (decreased number of functioning nephrons), leading to diminished ability to eliminate Na load
How to treat edema in renal failure and/or GN?
- Low salt diet
- Disturbances of water balance reflect Dysnatremias.
- Disturbances of volume
---- reflect sodium content abnormalities
---- involve abnormalities in Thirst mechanism, RAS and ADH.
- Volume depletion
- Volume overload
– Low salt diet and Diuretics. ACEI in Nephrotic Syndrome.