Homeostasis Flashcards
Normal plasma osmolality
275-295 mmol/kg
Normal plasma sodium range
135-145 mmol/L
Transudate
fluid pushes through the capillary due to high pressure within the capillary (low protein content)
Exudate
fluid that leaks around the cells of the capillary caused by inflammation and increased permeability of pleural capillaries to proteins (high protein content and may contain cells, bacteria, enzymes)
Diabetes insipidus
caused by the failure of the axons with cell bodies in the hypothalamus and synapses on blood vessels in the posterior pituitary to synthesize or release vasopressin (central diabetes insipidus) or the inability of the kidneys to respond to vasopressin (nephrogenic diabetes insipidus). Regardless of the type of diabetes insipidus, the permeability to water of the collecting ducts is low even if the patient is dehydrated.
Osmolality units
Concentration per kg
Osmolarity units
Concentration per L
Water distribution in a 70kg male: total body water
60% of body weight
42L
Water distribution in a 70kg male: intracellular fluid
40% of total
28L
Water distribution in a 70kg male: Extracellular fluid
20% of total
14L
Water distribution in a 70kg male: intravascular
3L
Water distribution in a 70kg male: Interstitial
11L
Extracellular fluid
• sodium is main contributor to osmolality and volume
• Anions = chloride and bicarbonate
• Glucose and urea
• Protein- colloid osmotic pressure (oncotic) eg albumin
Intracellular fluid
surrounds the cells but does not circulate
• predominant cation is potassium
Water intake
Drink
Diet
IV fluid
Water loss
Kidneys
Sweat
Breath
Vomiting
Faeces
Plasma osmolality
• largely determined by sodium and associated anions
• Estimated plasma osmolality= 2[Na] + 2[K] + urea + glucose mmol/L
• Intra- and extracellular osmolality are equal (isotonic)
• Change in plasma osmolality pulls or pushes water across cell membranes
How to estimate plasma osmolality
2[Na] + 2[K] + urea + glucose mmol/L
Why don’t we give water IV
it is hypo-osmolar/hypotonic vs cells
• Water enters blood cells causing them to expand an burst : haemolysis
• However, this only occurs in vicinity of the IV cannula
Extracellular fluid osmolality
very tightly regulates, changes lead to a rapid response.
Normal plasma osmolality 275-295 mmol/kg
Water deprivation or loss will led to a chain of events
Extracellular fluid volume
changes causes a slower response
Factors controlled by water homeostasis
ECF osmolality
ECF volume
Factors in calculated Osmolarity
• Na+
• K+
• urea
• glucose concentrations.
Dehydration causes…
- Movements of ICF to ECF
- Stimulation of thirst centre in hypothalamus
- Release of ADH from pituitary glands —>renal water retention
Causes of hypernatremia (water depletion)
• reduced intake
• Sweating
• Vomiting/diarrhoea/ diuretics/ diuresis
• drugs
• Sodium excess: mineralocorticoid (aldosterone) excess, salt poisoning
Symptoms of dehydration
Symptoms of dehydration:
• Thirst
• Dry mouth
• Inelastic skin
• Sunken eyes
• Raised haematocrit (proportion of blood made up of erythrocytes- less plasma)
• Weight loss
• Confusion – brain cells
• Hypotension
How much water is lost as a result of fever
Loose 500ml of water a day for every degree above 37
Where is ADH synthesised
Synthesised by the supraoptic and paraventricular nuclei of the hypothalamus.
Where is ADH stored
Posterior pituitary gland
What detects a low renal perfusion pressure due to low ECF volume
Juxtaglomerular in kidney
Renin-angiotensin-aldosterone system
Releases renin (kidney)
Renin cleaves angiotensinogen (liver) to form angiotensin I
Then cleaved by ACE (lungs) to form angiotensin II
Which enzyme cleaves angiotensinogen to form angiotensin I
Renin
Which enzyme cleaves angiotensin I to form angiotensin II
ACE
Where is renin produced
Kidney
Where is angiotensinogen produced
Liver
Where is ACE produced
Lungs
Functions of angiotensin II
Vasoconstriction of efferent renal arteriole
Aldosterone - Stimulation of sodium-hydrogen exchanger- increasing sodium reabsorption and water reabsorption in the kidney
Causes of hyponatraemia (water excess)
blood sodium level <135 mmol/L causing cells to swell as water moves into cells from blood
• Causes: excess water due to IV fluids, diuretics
Sodium loss: diuretics, Addison’s disease
Symptoms of water excess
Cerebral overhydration (headache, confusion, convulsions)- brain cells swell and so brain is crushed by skull
Hydrostatic pressure
pressure difference between plasma and interstitial fluid. Water moves from plasma into interstitial fluid
Oncotic pressure
pressure caused by the difference in protein concentration between the plasma and interstitial fluid. Water moves from interstitial fluid into plasma
What percentage of oncotic pressure is caused by albumin
75-80%
How does oncotic pressure change along a capillary
Stays the same
How does hydrostatic pressure change along a capillary
It decreases
Tissue fluid
A watery liquid made from blood plasma that bathes all cells and allows exchange of materials between blood and cells e.g. CO2 and glucose
Role of heart in tissue fluid formation
contraction of ventricle produces high blood pressure which forces water out
Formation of tissue fluid
- The hydrostatic pressure at the arteriole end of capillaries is greater inside capillaries than in the tissue fluid
- The difference in hydrostatic pressure means an overall outward pressure forces fluid out of the capillaries and into the spaces around the cells, forming tissue fluid
- As fluid leaves, the hydrostatic pressure falls so it is much lower at the venule end of the capillary
- Due to the fluid loss and an increasing concentration of plasma protein, the water potential at the venule end of the capillary bed is lower than the tissue fluid so some water re-enters the capillaries from the tissue fluid by osmosis
- Any excess tissue fluid is drained into the lymphatic system
Lymphatics
Lymph capillaries = a system of vessels that begin in tissues, have closed ends, large pores and valves
Lymph contains: tissue fluid, lymphocytes, fatty substances
Larger vessels drain their contents back into the bloodstream via two ducts that join veins close to the heart
Potential causes of oedema
High blood pressure → more tissue fluid pushed out at arterial end and less moves back in → fluid accumulates → oedema
higher salt concentration → lower water potential of blood → less water reabsorbed by osmosis from tissue fluid at venule end
Oedema
• excess accumulation of fluid in interstitial space
• Disruption of the filtration and osmotic forces of circulating fluids
• Obstruction of venous blood or lymphatic return
• Inflammation- increases capillary permeability
• Loss of plasma protein
Serous effusion
Excess water in a body cavity
Pathogenesis of oedema
increased fluid leakage into interstitial fluid or impaired transport ion of fluid
Inflammatory serous effusion
causes endothelial cells to become more permeable (in order for white blood cells to move out) so more fluid leaks out and cannot move back in as easily. Proteins leak out due to increased vascular permeability thereby Sikh to by the toxins, fibrinogen polymerises to form a fibrin mesh and immunoglobulins collect
Venous serous effusion
(common in lower leg) excess fluid doesn’t come back in at venous end due to increased venous pressure or venous obstruction from a thrombus
Lymphatic serous effusion
doesn’t drain correctly if blocked by a tumour or parasite eg in breast cancer if lymph nodes removed
Hypoalbuminaemic serous effusion
loss of blood so less albumin present (normally 75-80% pressure and 50% of plasma proteins) meaning lower oncotic pressure so less fluid moves back into veins- low oncotic pressure
What percentage of blood plasma protein is albumin
50%
Pleural effusion
• normal pleural space contains 10mL of fluid
• Balance between hydrostatic and oncotic forces in the visceral and parietal pleural vessels; lymphatic drainage
What does renin-angiotensinogen-aldosterone system have an effect on
• sympathetic nervous system- increases adrenaline, increases cardiac output, vasoconstriction
• Aldosterone secretion (kidneys retain more water and salt)
• ADH secretion
Disorders of plasma sodium
High or low [Na] are more often due to gain or loss of water
• Clinical effects are on the brain due to constricted volume in skull
• Rate of change is more important than absolute levels
• Aldosterone promotes sodium reabsorption in the kidneys.
Aldosterone
major control of tubular Na+ reabsorption is the adrenal cortical hormone aldosterone, which stimulates Na+ reabsorption in the cortical collecting ducts.
• Steroid hormone released from the adrenal cortex in response to stimulation by angiotensin II.
• It promotes sodium reabsorption and potassium secretion in the distal tubules of the kidneys.
Where is aldosterone released from
Adrenal cortex
A GP suspects that his young patient has cranial diabetes insipidus. This is a disorder in which the pituitary gland fails to release ADH when stimulated to do so. She is referred for a water deprivation test during which she is nil by mouth.
If the patient does have diabetes insipidus and is not producing any ADH which of the following is MOST LIKELY to show her blood and urine osmolality after 3 hours of water deprivation?
Blood 300/urine 100
Causes of hypercalcemia
hyperparathyroidism, Vit D toxicity, malignancy
Risks of hypercalcemia
renal stones and metastatic calcification
Causes of hypocalcemia
renal disease, Vit D deficiency, intestinal malabsorption
Risks of hypocalcemia
tetany (spasms)
Causes of Hyperkalemia (increased K+)
renal failure, acidosis, diuretic inhibitors
Risks of hyperkalemia
Cardiac arrest
Causes of Hypokalaemia (decreased K+)
D+V, alkalosis, diuretics
Risks of hypokalemia
Weakness and dysrhythmia
Where can sodium move freely
between interstitial and intravascular
Majority of sodium in skeleton
Osmolality
measure of the number of osmotically active solute particles dissolved in a kilogram of solvent
Why does low albumin lead to pitting oedema
low albumin result, meaning that he has a loss of plasma protein in his blood, so there is a lower oncotic pressure. So less fluid moves from the interstitial fluid into the plasma at the venule end of the capillary bed due to a smaller hydrostatic pressure gradient and so accumulates. This causes excess accumulation of fluid in interstitial space and so oedema. The colloid osmotic pressure is low, so fluid leaks into the interstitial space.
Causes of water depletion
Causes of water depletion:
• reduced intake
• Sweating
• Vomiting/diarrhoea/ diuretics/ diuresis
• drugs
• Urine/ faeces
• insensible water loss by evaporation from the respiratory tract and diffusion through the skin
Role of osmoreceptors in water homeostasis
osmoreceptors in the hypothalamus detect changes in osmotic pressure and so contribute to osmoregulation. When the osmotic pressure of blood changes, either more dilute or more concentrated, water diffusion into and out of the osmoreceptor cells occurs. The cells expand when the blood plasma is more dilute and contract with higher concentration. This causes a neural signal to be sent from the hypothalamus, which increases or decreases vasopressin secretion from the posterior pituitary to return blood concentration to normal. Also, stimulates thirst centre.
Role of kidney in water homeostasis
- Normally the glomerular filtrate has a similar osmolality to plasma (300 mOsmol/kg). In the descending limb of the loop of Henle, the NaCl cannot be absorbed, but water is passively resorbed , creating a hypertonic urine (>1200 mOsmol/kg) as it enters the ascending limb. 2. When this NaCl-rich fluid enters the NaCl-permeable (water-impermeable) thin ascending limb in the inner medulla, NaCl is absorbed passively along its concentration gradient without water. The absorbed NaCl in with urea absorbed from the collecting tubule lumen under the action of ADH create a hypertonic inner medulla which allows the passive diffusion of water out of the tubular lumen in the descending limb . The absorbed NaCl (and urea) is retained in the outer and inner medulla by the vasa recta blood supply (countercurrent exchange). 3. As the more concentrated urine enters the water-impermeable thick ascending limb of the loop of Henle, a Na-K-2Cl transporter actively pumps NaCl into the outer medulla without water, creating a dilute urine (around 100 mOsm/kg) as it enters the distal tubules. This is the pump that is inhibited by loop diuretics. Urea is retained in the tubular fluid (poorly absorbed in this region and may even enter the tubular lumen from the interstitium to some degree). 4. When the urine enters the last part of the distal tubule and first part of the collecting ducts in the outer medulla, water is absorbed passively along a concentration gradient established by the absorption of NaCl by the Na-K-2Cl carrier in the ascending limb. This begins to concentrate the urine. 5. Urine is maximally concentrated under the influence of ADH, which opens water channels (aquaporins) in the collecting tubules in the inner medulla and allowing water to flow along the concentration gradient already established by the countercurrent mechanism in the loop of Henle. The absorption of urea, under the influence of ADH, contributes substantially to the medullary interstitial osmotic gradient.
Role of thirst centre in water homeostasis
As the blood becomes more concentrated, the thirst response—a sequence of physiological processes—is triggered. Osmoreceptors are sensory receptors in the thirst center in the hypothalamus that monitor the concentration of solutes (osmolality) of the blood. If blood osmolality increases above its ideal value, the hypothalamus transmits signals that result in a conscious awareness of thirst. The person should (and normally does) respond by drinking water.
Sodium homeostasis - PCT
67% of the sodium in the tubule lumen is reabsorbed in the proximal convoluted tubule or in the PCT. In the early PCT, sodium is reabsorbed together with other molecules, through 3 different channels found on the surface of tubular cells. Sodium and glucose are reabsorbed together through the sodium-glucose cotransporter, sodium and amino acids are also reabsorbed together through the sodium- amino acid cotransporter and finally, phosphate and sodium are reabsorbed together through the sodium-phosphate cotransporter.
Finally, in the early PCT there’s also a sodium-hydrogen exchanger, which is a cell membrane protein that reabsorbs sodium in exchange for hydrogen. And this is mainly regulated by a molecule called angiotensin II, which is a product of the renin-angiotensin-aldosterone system. Renin (kidney) stimulates angiotensinogen (liver) conversion into angiotensin I which is then converted into angiotensin II.
Angiotensin II has many functions, some of which include vasoconstriction of the efferent renal arteriole and stimulating the sodium-hydrogen exchanger. In turn, this increases sodium reabsorption and water reabsorption, in order to bring up blood pressure.
Second, in the late PCT, sodium is still reabsorbed through the sodium-hydrogen exchanger, and also along with chloride, through the chloride-formate exchanger. This transporter reabsorbs chloride and secretes formate, which is a negative ion derived from formic acid.
In the late PCT, sodium and chloride can also get reabsorbed through a paracellular way, meaning that they don’t use any channels, but rather they sneak between two epithelial cells and go back into the bloodstream.
Sodium homeostasis - loop of henle
About 25 percent of the sodium is further reabsorbed in the thick ascending loop of Henle. In the TAL, sodium is reabsorbed, along with potassium and chloride, through the sodium-potassium-chloride cotransporter, also called NKCC2.
An important regulatory mechanism here is antidiuretic hormone or ADH, which is secreted by the posterior part of the pituitary gland, up in the brain, in response to decreased blood volume or increased blood osmolality - so when there are too many solutes compared to water in the blood. When secreted, this stimulates NKCC2, increasing sodium, chloride and potassium reabsorption.
In the early distal tubule, 5 percent of the filtered sodium is reabsorbed and a sodium chloride cotransporter that reabsorbs both sodium and chloride.
What affects sodium homeostasis
Aldosterone is secreted in response to low blood pressure, and it induces the synthesis of more ENaC channels, which allows for more sodium to be reabsorbed, so blood pressure increases.
The sympathetic nervous system, which activates when there’s a decrease in blood pressure, and causes vasoconstriction of the afferent arterioles in the glomerulus. Additionally, it also increases sodium reabsorption in the proximal tubule.
At the other end of the spectrum, there is atriopeptin or ANP which is secreted by the atria when the EABV is increased - so high blood pressure. ANP causes vasodilation of the afferent arterioles and vasoconstriction of the efferent arterioles which increases the glomerular filtration rate - so more blood is filtered by the glomerulus. ANP also inhibits ENaC channels in the late distal tubule and collecting ducts, decreasing sodium reabsorption. So more sodium and water are eliminated, decreasing blood pressure.
Other peptides similar to ANP include urodilatin which is secreted by the kidneys themselves, and the brain natriuretic peptide or BNP which is secreted by the cardiac ventricular cells. They are also secreted in response to high blood pressure and act just like ANP to bring it down, but they have a lower intensity.
Sodium homeostasis- LDT and collecting ducts
In the late distal tubule and the collecting ducts, the remaining 3% of filtered sodium is reabsorbed. The principal cells, which have epithelial sodium channels, or ENaC for short, on their surface. Sodium is reabsorbed by ENaCs in response to aldosterone, which is the final product of the renin angiotensin aldosterone system.
Aldosterone is secreted in response to low blood pressure, and it induces the synthesis of more ENaC channels, which allows for more sodium to be reabsorbed, so blood pressure increases.
How does ANP decrease blood pressure
secreted by the atria when the EABV is increased - so high blood pressure. ANP causes vasodilation of the afferent arterioles and vasoconstriction of the efferent arterioles which increases the glomerular filtration rate - so more blood is filtered by the glomerulus. ANP also inhibits ENaC channels in the late distal tubule and collecting ducts, decreasing sodium reabsorption. So more sodium and water are eliminated, decreasing blood pressure.
Other peptides similar to ANP include urodilatin which is secreted by the kidneys themselves, and the brain natriuretic peptide or BNP which is secreted by the cardiac ventricular cells. They are also secreted in response to high blood pressure and act just like ANP to bring it down, but they have a lower intensity.
How does sympathetic nervous system increase blood pressure
sympathetic nervous system, which activates when there’s a decrease in blood pressure, and causes vasoconstriction of the afferent arterioles in the glomerulus. Additionally, it also increases sodium reabsorption in the proximal tubule.
Normal homeostatic response to excess fluid
Osmoreceptor cells in the hypothalamus detect the RISE in water potential (stimulated by higher blood volume, decreased of serum osmolality), causing the paraventricular, supraoptic neurons of hypothalamus to produce less ADH (antidiuretic hormone)
Less ADH passes into the posterior pituitary gland via axons through infundibulum where it is secreted into the capillaries
ADH passes in the blood to the kidney, where it decreases the permeability of the DCT and collecting duct walls
• this decreases the number of aquaporin in the membrane, making it less permeable to water (as well as urea)
• therefore, less water leaves and moves into interstitial fluid then capillaries by osmosis- larger volume of dilute urine produced (hypotonic)
Dangers of excess water consumption
• hyponatraemia- blood sodium level <135 mmol/L causing cells to swell as water moves into cells from blood
• Cerebral overhydration (headache, confusion, convulsions)- brain cells swell and so brain is crushed by skull
• Nausea and vomiting
• Discolouration of hands, feet and lips due to swelling of cells
• Drowsiness and fatigue
• Muscle weakness or cramping
• Difficulty breathing
• Double vision
Normal response to dehydration
Dehydration: plasma osmolarity increases and blood pressure decreases
Osmoreceptor cells in the hypothalamus detect the FALL in water potential (stimulated by low blood volume, increase of serum osmolality and angiotensin II), causing the paraventricular, supraoptic neurons of hypothalamus to produce ADH (antidiuretic hormone)
ADH passes into the posterior pituitary gland via axons through infundibulum where it is secreted into the capillaries
ADH passes in the blood to the kidney, where it increases the permeability of the DCT and collecting duct walls
• V2 protein receptors (AVPR2) on basolateral membrane of principal cells bind to ADH, activating the enzyme adenylyl cyclase to convert ATP to cAMP
• this cause vesicles (containing plasma membrane embedded with aquaporin) within the cell to more to and fuse with cell-surface membrane
• this increases the number of aquaporin in the membrane, making it more permeable to water (as well as urea) which diffuses out, lowering the water potential of fluid around the duct
• therefore, more water leaves and moves into interstitial fluid then capillaries by osmosis- smaller volume of concentrated urine produced (hypertonic)
Also sends nerve impulses to thirst centre to encourage drinking and increase water uptake.
Also a decrease in ECF volume:
Detected by juxtaglomerular in kidney
Releases renin
Renin cleaves angiotensinogen (from liver) to form angiotensin I
Then cleaved by ACE (angiotensin-converting enzyme) (from lungs) to form angiotensin II
Has effect on:
• sympathetic nervous system- increases adrenaline, increases cardiac output, vasoconstriction
• Aldosterone synthesis and secretion in the glomerulosa cells of adrenal gland- causing Na+ reabsorption to increase in the principal cells of renal distal tubule and collecting duct. Increased Na+ concentration leads to increased osmolarity and so increase ECF and blood volume (kidneys retain more water and salt)
Which receptors on basolateral membrane of principal cells bind to ADH
V2 protein receptors (AVPR2)
What does angiotensin II have an effect on
• sympathetic nervous system- increases adrenaline, increases cardiac output, vasoconstriction
• Aldosterone synthesis and secretion in the glomerulosa cells of adrenal gland- causing Na+ reabsorption to increase in the principal cells of renal distal tubule and collecting duct. Increased Na+ concentration leads to increased osmolarity and so increase ECF and blood volume (kidneys retain more water and salt)
What effect does hypercalcaemia have on muscle and nerve function
Both muscle and nerve activity will be depressed
Increases inhibition of sodium channels, raising threshold for depolarisation
- What is the relationship between albumin and oedema?
Low albumin leads to decrease in oncotic pressure, this causes water to diffuse from the blood into the interstitial fluid
- What are the sites of synthesis of: ADH, aldosterone and renin?
- ADH is produced in the hypothalamus, aldosterone is produced in the adrenal cortex, renin is produced by the juxtaglomerular cells in the kidney
