Polyuria/Polydipsia Flashcards
Major routes for water intake and loss (and regulatory mechanisms)
Intake: ~2400ml/day
2000ml/day from ingestion
400ml/day from metabolism
Kidney is the most important organ for water regulation (physiological)
Other (skin, intestine, lungs) become important in pathological circumstances
Regulated by:
1. Updake: mechanism of thirst
2. Elimination: reabsorption in the kidney
Without the kidneys, we’d balloon, have constant edema (accumulation of fluid in the body)
How does osmolarity influence fluid movement
Starling forces
How does osmolarity influence fluid movement
Starling: exchange of water depends on different forces
Arterial: BP 30mmHg arriving to capillaries (mean arterial pressure 100mmHg), 30 pushing out of capillaries
Oncotic pressure: Due to proteins present in body; brings water back in (about 20 mmHg) constant along vessel
Venous: BP drops to 10 mmHg
Difference of 20 mmHg between arterial and venous (equals oncotic pressure)
Creates a movement of fluid between vessel and interstitia
10mmHg is the difference favoring water efflux from vessel AND water entrance: it’s identical
Sensors and effector pathways involved in regulation of ECF volume
- Effective circulating volume is sensed
- Baroreceptors and volume receptor sensors
- Antidiuretic hormone (AVP), atrial natriueritc peptide (ANP), Renin-angiotensin-aldosterone, sympathetic nerve activity effector pathways
- Short term effects: heart, blood vessels; long term: kidney
- Short term regulation: blood pressure
Long term regulation: Na+ excretion
Response of baroreceptors and volume receptors to changes in the effective volume and how these responses affect salt and water excretion by kidney
Maintaining ECF volume is 1 of 2 ways to regulate water balance
Total body Na+ is maintained through the diet
Leads to ECF volume
Baro/volume sensors located in veins, atrium, parts of vascular tissues signal effector pathways that signal Na+ excretion by the kidney (water will follow)
How do changes in osmolality caused by water and/or salt gain or loss alter the rate of urine production and the osmotic composition of urine
1 of 2 ways water balance is carried out: Maintaining osmolarity
Osmolarity is controlled by controlling the main electrolyte in our ECF (Na+)
Na+ regulated by adding or subtracting water
Water regulated by intake or excretion
Water follows solute
How does ADH change the ability of the kidney to produce diluted or concentrated urine
As pressure and volume go down, ADH goes up
Basal plasma osmolality: 285-290; beyond this, ADH increases
As ADH increases, urine flow rate will decrease. More water is being reabsorbed and less is being excreted
As ADH increases, osmolarity is increasing (urine becoming more concentrated, darker)
General functions of kidney (3)
- Homeostatic
Regulation of ECF volume
Regulation of electrolyte composition
Regulation of ECF fluid acid-base balance (important for pH maintenance with specific electrolyte H+) - Excretory
Metabolic waste products
Foreign substances and toxins - Endocrine
Regulation of blood pressure
Erythropoiesis (production of RBCs when low O2 is detected by kidneys)
Calcium metabolism
General functions of kidney (3)
- Homeostatic
Regulation of ECF volume
Regulation of electrolyte composition
Regulation of ECF fluid acid-base balance (important for pH maintenance with specific electrolyte H+) - Excretory
Metabolic waste products
Foreign substances and toxins - Endocrine
Regulation of blood pressure
Erythropoiesis (production of RBCs when low O2 is detected by kidneys)
Calcium metabolism
To filter everything from the blood except cells and proteins
Causes of Polyuria
Causes:
- Low solute reabsorption (if you aren’t absorbing the salt, water will not be reabsorbed- Solute diuresis)
- Abnormal ADH levels (water diuresis- if you don’t have ADH, you can’t reabsorb water)
Causes, diagnosis, and treatment of polydipsia
Excessive water ingested
Primary polydipsia is a form of polydipsia characterised by excessive fluid intake in the absence of physiological stimuli to drink. This includes psychogenic polydipsia (PPD), which is caused by psychiatric disorders, often schizophrenia, and often accompanied by the sensation of dry mouth.
How does the increase in glucose delivered to the kidney result in high urine output?
If glucose is not reabsorbed by the kidney, it appears in the urine, in a condition known as glucosuria.
This is associated with diabetes mellitus. Firstly, the glucose in the proximal tubule is co-transported with sodium ions into the proximal convoluted tubule walls via the SGLT2 cotransporter.
With regard to renal reabsorption of glucose, the kidneys normally retrieve as much glucose as possible, rendering the urine virtually glucose free. The glomeruli filter from plasma approximately 180 grams of D-glucose per day, all of which is reabsorbed through glucose transporter proteins that are present in cell membranes within the proximal tubules. If the capacity of these transporters is exceeded, glucose appears in the urine. The process of renal glucose reabsorption is mediated by active (sodium-coupled glucose cotransporters) and passive (glucose transporters) transporters
Hyperglycemia exceeds renal ability to resorb glucose
Solute diuresis (3 causes) - osmotic diuresis
Diuresis: production of urine by the kidney
When the production of urine depends on the solute
Causes:
1. Salt wasting
2. Diuretics (drug that make you pee more)
Treatment for hypertension, peeing makes you release water, lowering blood pressure; inhibits salt reabsorption, inhibiting water reabsorption
3. High glucose in renal tubule
High glucose in renal tubule, water follows glucose. why DM patient will have polyuria
4. Osmolytes in filtrate
Excess solutes in filtrate >
Decreased water reabsorption in proximal >
Partial, insufficient reabsorption compensation by distal >
Urine osmolarity isotonic or close to plasma >
Increased urine volume
Causes: Diabetes mellitus Fanconi syndrome Inhibition of salt reabsorption by drugs (diuretics) Decreased aldosterone
Water diuresis
Excess water ingested (caused by polydipsia [psychogenic]- could be caused by polyuria or could cause) >
Decreased extracellular fluid osmolarity >
Decreased ADH secretion (also caused by diabetes insipidus) >
Decreased nephron permeability and water reabsorption >
Solute reabsorption continues >
Increased urine dilution
Causes:
Primary polydipsia - psychogenic
Diabetes insipidus (central or nephrogenic)
The countercurrent principle (loop of Henle)
In the loop of Henle: job is to create a very diluted fluid
Ascending loop
Has transporters that move Na+ out of the tubule and into the kidney (medulla gets saturated/salty with Na+). Some salt goes back into descending tubule (recycles around)
Descending loop:
Water follows the solute and goes into the intestitium
Ascending loop:
Water flows through but can’t move out into interstitium because ascending loop is completely impermeable to water
Fluid becomes more dilute because water is being retained but Na+ is lowing out
The countercurrent principle (loop of Henle)
In the loop of Henle: job is to create a very diluted fluid**
Ascending loop
Has transporters that move Na+ out of the tubule and into the kidney (medulla gets saturated/salty with Na+). Some salt goes back into descending tubule (recycles around)
Descending loop:
Water follows the solute and goes into the intestitium
Ascending loop:
Water flows through but can’t move out into interstitium because ascending loop is completely impermeable to water
Fluid becomes more dilute because water is being retained but Na+ is lowing out
Countercurrent mechanism continued: What happens after the loop of Henle?
The very dilute fluid from the loop of henle now passes through a VERY salty medulla
Moving through distal and collecting tubules
Water wants to move out into the medulla to make it less salty, but can’t unless ADH is present to make tubule more permeable
ADH opens the gates, water follows gradient and is reabsorbed, less water comes out in the urine
Diabetic nephropathy
- Thickening of membrane affects filtration mechanism
- Arteriolosclerosis increases pressure, thickened walls, decreased lumen, decreased blood flow,
- Messangial and glomerular expansion, creating protein deposits (Kimmestiel Wilson nodules)
- Disruption of podocytes (cells in Bowman’s capsule that wrap around capillaries of glomerulus, ruining glomerulus, leading to renal failure)
Diabetic nephropathy
- Thickening of membrane affects filtration mechanism
- Arteriolosclerosis increases pressure, thickened walls, decreased lumen, decreased blood flow, more filtration
- Messangial and glomerular expansion, creating protein deposits (Kimmestiel Wilson nodules)
- Disruption of podocytes due to Hyaline deposits (cells in Bowman’s capsule that wrap around capillaries of glomerulus responsible for letting filtrate in)
ruining glomerulus, leading to renal failure)
Diabetic nephropathy (characteristics)
- Thickening of capillary and tubular basement membrane affects filtration mechanism
- Vascular changes: Atherosclerosis, Arteriolosclerosis increases pressure, thickened walls, decreased lumen, decreased blood flow, more filtration, more urine
- Messangial and glomerular expansion, creating protein deposits (Kimmestiel Wilson nodules)
- Disruption of podocytes due to Hyaline deposits ruins glomerulus (cells in Bowman’s capsule that wrap around capillaries of glomerulus responsible for letting filtrate in)
Leads to hypofiltration, leading to renal failure)
Initially, this causes glomerular hyperfiltration (may be associated with transient increase in GFR),
but ultimately this leads to formation of nodular and hyaline deposits and glomerulosclerosis with the glomerular ischemia.
Eventually leading to tubular atrophy and interstitial fibrosis, with overall loss of cortical mass and decrease in renal size with scarring.
Solute diuresis in DM
Glucose is reabsorbed in the tubules, but if the mechanisms that reabsorb it become saturated, glucose will appear in the urine
High plasma glucose >
Increased glucose filtration >
Glucose remains in tubule >
Increased diuresis
Diabetes insipidus
Clinical features based on loss of free water
- Polyuria/polydipsia
- Hypernatremia or high serum osmolality
- Low urine osmolality or specific gravity
Water deprivation test fails to increase urine osmolality
Central: Lack of ADH
Due to hypothalamic or posterior pituitary pathology (tumor, trauma, infection, inflammation) genetic causes, hypoxic encephalopathy, or pituitary surgery
Treatment is desmopressin (ADH analog)
Nephrogenic: Receptors that respond to ADH are not working
Due to drugs (lithium) or reduced renal response from inherited mutations
No response to desmopressin
Diagnosis of polyuria
Diagnosis: (tests)
- Water restriction (not drink water for a while), monitor urine osmolarity and volume, plasma and urine, plasma and urine levels
- Administer hypertonic saline (raise osmolarity and see how kidneys respond), measure plasma ADH levels, consider diabetes mellitus
Graph for normal (plasma osmolarity and urine volume/osmolarity)
Plasma osmolarity increases, urine osmolarity increases
Plasma osmolarity increases, urine volume decreases
As plasma osmolarity increases, water is reabsorbed (ADH is released), urine comes at higher concentration
Injecting patients with vasopressin (ADH) won’t change anything because they have already absorbed water and ADH levels are maximal
