Guided Studies W5/6

Question 1

Define the term clearance.

Answer 1

“Clearance” is a term which describes the amount of plasma entering the kidneys per minute that has been ‘cleared’ of a substance.

Question 2

What is the formula for clearance ?

Answer 2

Clearance = ((urine concentration of X) x (urine flow rate)) / plasma concentration of X

Question 3

Describe excretion of glucose, inulin, and PAH and conclude clearance from this.

Answer 3

Glucose which is freely filtered, but then reabsorbed back into the blood, the amount of plasma cleared of glucose is 0 (because the concentration of glucose in the renal vein is the same as the concentration in the renal artery.)

Inulin, is freely filtered, but then is neither reabsorbed, nor secreted, the clearance is the same as the glomerular filtration rate (GFR). The concentration in the renal vein is slightly lower than in the renal artery.

PAH freely filtered and also actively secreted, the amount of plasma cleared of PAH is the total amount of plasma that enters the kidneys. The concentration of PAH leaving the renal vein is zero.

Question 4

Where is EPO released ?

Answer 4

In adults, it is released by the liver (small proportion) and the kidney (major source). In premature babies and neonates, the liver is the major source, but this switches to the kidney with time.

Question 5

What is the main role of EPO ?

Answer 5

Stimulates erythrocyte production. Circulating erythropoietin stimulates bone marrow cells that are committed to becoming red blood cells. As a consequence, the reticulocyte (young red blood cell) levels in the blood rise rapidly.

Question 6

List causes of EPO production.

Answer 6

If the cells of the kidney become hypoxic, they increase their release of erythropoietin. Typical triggers of erythropoietin include:

• being at altitude
• loss of red blood cells due to haemorrhage or excessive red blood cell destruction
• increased tissue oxygen demands
• red blood cells that have a reduced oxygen carrying capacity

Question 7

What is the main factor regulating the release of EPO?

Answer 7

The absolute levels of red blood cells do not determine the release of erythropoietin, but their ability to carry oxygen.

Question 8

What happens to EPO production oxygen carrying capacity of the blood rises ?

Answer 8

Once the oxygen carrying capacity of the blood rises, the stimulus to release erythropoietin falls.

Question 9

How long would it take for reticulocyte count to increase after a hemorrhage ?

Answer 9

1 or 2 days

Question 10

Identify any causes of pathological drops in EPO. What are the symptoms which result from this ? What treatment is used to counter this ?

Answer 10

As chronic renal failure progresses, the scarring that occurs leads to a decrease in functioning cells and a drop in the release of erythropoietin. As a consequence, there is a reduced capacity of the blood to carry oxygen and the patient may present with lethargy as a result of anaemia.
Synthetic erythropoietin is now used in therapy to counter these effects.

Question 11

Describe the role of the kidney wrt vitamin D.

Answer 11

The kidneys synthesise 1, 25-dihydroxycholecalciferol (calcitriol) from vitamin D.

Question 12

Describe the process of Calcitriol formation in the kidney. What can inhibit and promote this reaction ?

Answer 12

1) Vitamin D is hydroxylated by the liver to
produce 25-hydroxycholecalciferol.
2) The kidneys the add a further hydroxyl group to convert
it to 1,25-dihydroxycholecalciferol (also called calcitriol).
—–
This reaction is promoted by parathyroid hormone and inhibited by high plasma phosphate levels.

Question 13

Identify the main roles of Calcitriol.

Answer 13

-Stimulates the absorption of ingested calcium. It does so by increasing the expression of calcium channels used to transport calcium across the cell membrane of the intestinal mucosa.
-Phosphate absorption is also increased.
-In addition, there is stimulation of calcification of bone matrix, partly as a result of increased calcium and
phosphate levels in the plasma, but also by direct stimulation of osteoblasts and osteoclasts,
facilitating the remodelling of bone.

Question 14

Identify any causes of pathological drops in Calcitriol. What are the symptoms which result from this ?

Answer 14

In renal failure, 25-hydroxycholecalciferol is not converted to 1,25-dihydroxycholecalciferol, which can lead to hyperparathyroidism (due to the reduced circulating calcium levels stimulating growth of the gland), osteomalacia (softening of the bones) and osteoporosis (loss of bone tissue leading to brittle bones).

Question 15

Describe the main effects of chronic renal failure on bone.

Answer 15

1) Reduces Calcitriol:
- osteomalacia
- osteoporosis

Question 16

Explain why some think there’s hypocrisy in the current situation of organ donation, where donors are not paid.

Answer 16

“There is a lot of hypocrisy about the ethics of buying and selling organs and indeed other body products and services—for example, surrogacy and gametes. What it usually means is that everyone is paid but the donor. The surgeons and medical team are paid, the transplant coordinator does not go unremunerated, and the recipient receives an important benefit in kind. Only the unfortunate and heroic donor is supposed to put up with the insult of no reward, to add to the injury of the operation.”

Question 17

Support the idea that there is a need to increase the supply of organs for transplantation.

Answer 17

As of 2002 in the UK, 5615 people are still awaiting transplants

Question 18

Discuss the risks and benefits of living organ donation.

Answer 18

PROS:

• excellent prognosis, better than cadaver organ transplantation
• creating a market in cadaver organs is uneconomic and is more likely to reduce supply than increase it and the chief reason for considering sale of organs is to improve availability
• risks of live donation are relatively low: “The approximate risks to the donor are a short term morbidity of 20% and mortality, of 0.03%”(the long term risks of developing renal failure are less well documented but appear to be no greater than for the normal population)
• “timing can be controlled in order to optimize pretransplant treatment”

CONS:
-“clear learning curve for surgeons. Outcomes do not get better until the surgeon has performed 20 or 30 procedures.” (i.e. risk still present)

Question 19

Outline the model for organ sales that Charles A Erin and John Harris propose in this paper.

Answer 19

1) “The market would be confined to a self governing geopolitical area such as a nation state or indeed the European Union. Only citizens resident within the union or state could sell into the system and they and their families would be equally eligible to receive organs. Thus organ vendors would know they were contributing to a system which would benefit them and their families and friends since their chances of receiving an organ in case of need would be increased by the existence of the market.
2) There would be only one purchaser, an agency like the NHS, which would buy all organs and distribute according to some fair conception of medical priority. There would be no direct sales or purchases, no exploitation of low income countries and their populations.
3) The organs would be tested for HIV, etc, their provenance known, and there would be strict controls and penalties to prevent abuse.
4) Prices would have to be high enough to attract people into the marketplace but dialysis, and other alternative care, does not come cheap. Sellers of organs would know they had saved a life and would be reasonably compensated for their risk, time, and altruism, which would be undiminished by sale.

Question 20

What proportion of a healthy young man is water ? healthy young woman ?

Answer 20

60%

50%

Question 21

List the fluid compartments within the body and their approximate values.

Answer 21

Intracellular Fluid: 25L

Extracellular Fluid (15L)
Plasma: 3L
Interstitial Fluid: 12L

Question 22

State the difference between electrolytes and non-electrolytes. Give examples of both.

Answer 22

Nonelectrolytes have bonds (usually covalent bonds) that prevent them from dissociating in solution; therefore, no electrically charged species are created when nonelectrolytes dissolve in water. Most nonelectrolytes are organic molecules–glucose, lipids, creatinine, and urea, for example

Electrolytes are chemical compounds that do dissociate into ions in water. Because ions are charged particles, they can conduct an electrical current–hence the name electrolyte. Typically, electrolytes include inorganic salts, both inorganic and organic acids and bases, and some proteins.

Question 23

Which of electrolytes or non electrolytes has higher osmotic power ?

Answer 23

Electrolytes have much greater osmotic power than nonelectrolytes because each electrolyte molecule dissociates into at least two ions. For example, a molecule of sodium chloride (NaCl) contributes twice as many solute particles as glucose (which remains undissociated), and a molecule of magnesium chloride (MgCl 2 ) contributes three. Regardless of the type of solute particle, water moves according to osmotic gradients–from an area of lesser osmolality to an area of greater osmolality. Thus, electrolytes have the greatest ability to cause fluid shifts.

Question 24

State the MAJOR differences in composition between ICF and ECF.

Answer 24

• In contrast to extracellular fluids, the ICF contains only small amounts of Na + and Cl - . Its most abundant cation is potassium, and its major anion is HPO 4 2- . Cells also contain substantial quantities of soluble proteins (about three times the amount found in plasma).

i.e. sodium and potassium ion concentrations in ECF and ICF are nearly opposite.

Question 25

What causes fluid to move between the different compartments of the body ?

Answer 25

1) Exchanges between plasma and IF occur across capillary membranes. Nearly protein-free plasma is forced out of the blood into the interstitial space by the hydrostatic pressure of blood. This filtered fluid is then almost completely reabsorbed into the bloodstream in response to the colloid osmotic (oncotic) pressure of plasma proteins. Under normal circumstances, the small net leakage that remains behind in the interstitial space is picked up by lymphatic vessels and returned to the blood.
2) Exchanges between the IF and ICF: As a general rule, two-way osmotic flow of water is substantial. But ion fluxes are restricted and, in most cases, ions move selectively by active transport. Movements of nutrients, respiratory gases, and wastes are typically unidirectional. For example, glucose and oxygen move into the cells and metabolic wastes move out.
3) Plasma circulates throughout the body and links the external and internal environments. Exchanges occur almost continuously in the lungs, gastrointestinal tract, and kidneys. Although these exchanges alter plasma composition and volume, compensating adjustments in the other two fluid compartments follow quickly so that balance is restored.

Question 26

Identify factors which can change ICF and ECF Volumes.

Answer 26

Increasing the ECF solute content (mainly the NaCl concentration) can be expected to cause osmotic and volume changes in the ICF–namely, a shift of water out of the cells. Conversely, decreasing ECF osmolality causes water to move into the cells. Thus, the ICF volume is determined by the ECF solute concentration.

Question 27

Identify the routes by which the body gains and loses water.

Answer 27

1) Water intake
- Thirst

2) Water output
- Feces (obligatory loss)
- Urine (obligatory loss)
- Insensible losses (through skin/respiratory loss)
- Other e.g. drains, blood loss

Question 28

Draw a flow chart explaining the thirst mechanism.

Answer 28

Refer to diagram in Marieb Unit 4 Chapter 26 Section “Water Balance and ECF Osmolarity”, Water Intake.

Question 29

Explain the mechanisms and consequences of ADH release.

Answer 29

Refer to diagram in Marieb Unit 4 Chapter 26 Section “Water Balance and ECF Osmolarity”, Influence of ADH.

Question 30

Identify the common causes of disturbance in water balance.

Answer 30

1) Dehydration
2) Hypotonic Hydration
3) Edema

Question 31

Identify the causes, signs and symptoms of dehydration.

Answer 31

♠ Causes: hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse sweating, water deprivation, and diuretic abuse. Dehydration may also be caused by endocrine disturbances, such as diabetes mellitus or diabetes insipidus.

♠ Signs and Symptoms: “cottony” or sticky oral mucosa, thirst, dry flushed skin, and decreased urine output (oliguria). If prolonged, dehydration may lead to weight loss, fever, and mental confusion. Another serious consequence of water loss from plasma is inadequate blood volume to maintain normal circulation and ensuing hypovolemic shock .

Question 32

What are the main consequences of dehydration to the fluid compartments ?

Answer 32

In all these situations, water is lost from the ECF. This is followed by the osmotic movement of water from the cells into the ECF, which equalizes the osmolality of the extracellular and intracellular fluids even though the total fluid volume has been reduced. Though the overall effect is called dehydration, it rarely involves only a water deficit, because most often electrolytes are lost as well.

Question 33

Define dehydration.

Answer 33

When water output exceeds intake over a period of time and the body is in negative fluid balance.

Question 34

Identify the causes, signs and symptoms of hypotonic hydration.

Answer 34

♦ Causes: renal insufficiency or when an extraordinary amount of water is drunk very quickly

♦ Signs and symptoms: resulting electrolyte dilution leads to severe metabolic disturbances evidenced by nausea, vomiting, muscular cramping, and cerebral edema. Hypotonic hydration is particularly damaging to neurons. Uncorrected cerebral edema quickly leads to disorientation, convulsions, coma, and death.

Question 35

What are the main consequences of hypotonic hydration to the fluid compartments ? How is this treated ?

Answer 35

♦ Consequences: ECF is diluted–its sodium content is normal, but excess water is present. Thus, the hallmark of this condition is hyponatremia (low ECF Na + ), which promotes net osmosis into the tissue cells, causing them to swell as they become abnormally hydrated.

♦ Treatment: intravenous administration of hypertonic mannitol, which reverses the osmotic gradient and “pulls” water out of the cells.

Question 36

Define edema.

Answer 36

Atypical accumulation of fluid in the interstitial space, leading to tissue swelling

Question 37

Identify the causes, signs and symptoms of edema.

Answer 37

• Causes:

1) Factors that accelerate fluid loss from the blood, including a) increased blood pressure and b) capillary permeability.
a) Increased capillary hydrostatic pressure can result from incompetent venous valves, localized blood vessel blockage, congestive heart failure, or high blood volume. The abnormally high capillary hydrostatic pressure intensifies filtration at the capillary beds.
b) Increased capillary permeability is usually due to an ongoing inflammatory response.

2) Factors that hinder fluid return to the blood
- hypoproteinemia results in tissue edema because protein-deficient plasma has an abnormally low colloid osmotic pressure. Fluids are forced out of the capillary beds at the arterial ends by blood pressure as usual, but fail to return to the blood at the venous ends. Thus, the interstitial spaces become congested with fluid. Hypoproteinemia may result from protein malnutrition, liver disease, or glomerulonephritis
- lymphatic vessels are blocked or have been surgically removed

Question 38

What are the main consequences of edema on the fluid compartments ?

Answer 38

The small amounts of plasma proteins that seep out of the bloodstream are not returned to the blood as usual. As the leaked proteins accumulate in the IF, they exert an ever-increasing colloid osmotic pressure, which draws fluid from the blood and holds it in the interstitial space. Because excess fluid in the interstitial space increases the distance nutrients and oxygen must diffuse between the blood and the cells, edema can impair tissue function. However, the most serious problems resulting from edema affect the cardiovascular system. When fluid leaves the bloodstream and accumulates in the interstitial space, both blood volume and blood pressure decline and the efficiency of the circulation is severely impaired.

Question 39

Identify the amount of fluid lost through the main fluid losses of the body, and the total amount of fluid loss in a day.

Answer 39

Urine: 1500 – 2000mls
GI loss: negligible
“Insensible” losses: 500mls
Other e.g. drains, blood loss: variable

average between 2000 – 3000mls /day

Question 40

Identify factors which increase, and decrease fluid loss through urine.

Answer 40

+: Diuresis, diuretics

-: Obstruction, fluid loss, illness, trauma, surgery

Question 41

Identify factors which increase fluid loss through GI loss.

Answer 41

• Diarrhoea
• Vomiting
• Ileostomies
• Laxatives

Question 42

Identify factors which increase fluid loss through insensible losses.

Answer 42

Fever, sweating

Question 43

How much do healthy adults require in fluid intake per day ? Other categories of patients ?

Answer 43

The average adult who is not sick requires approximately 30mls/kg/24 hours of fluids – so for adults this
equates to roughly 2000mls – 3000mls fluids.

Elderly patients, or those with renal impairment or cardiac failure or malnourished patients may require less fluids in the region of 20-25mls/kg/24 hours.

Question 44

State the approximate electrolyte and glucose requirements for routine replacement.

Answer 44

• Sodium, Potassium, Chloride 1 mmol/kg/24 hours

* 50-100g glucose per day to limit starvation ketones.

Question 45

Upon inspection, identify any clues which may indicate that a patient is dehydrated.

Answer 45

Cups of water/juice, fluid restriction signs, catheter bags, drains, nutritional supplements or current infusions in
place?

Question 46

What are some causes of fluid overload ?

Answer 46

cardiac, hepatic and renal failure, excessive sodium ingestion (either oral or IV)

Question 47

What are the best measures of hydration status ?

Answer 47

1) Urine output is a good measure of hydration status – when the body is dehydrated the kidneys hold on to
as much fluid as possible and so urine tends to be more concentrated.
2) Urinalysis to look at colour and presence of ketones, glucose, possible infection, and measurement of specific gravity (concentration of urine).

Question 48

Identify signs and symptoms of a HypoV patient.

Answer 48

Dry mucous membranes, cool peripheries, tachycardia, reduced capillary fill time, postural hypotension, oliguria (abnormally small amounts of urine) and confusion. There may be a history of fluid loss or low intake.

Question 49

Identify signs and symptoms of a HyperV patient.

Answer 49

patient oedematous (check for sacral, ascites and peripheral oedema), may have inspiratory crackles, high JVP and history/ fluid charts show fluid overload. Fluid
overload may cause basal crepitations due to pulmonary oedema so check lung bases. There may
be hypertension and reduced oxygen saturations.

Question 50

What investigations/management should be performed in a hypoV patient ?

Answer 50

1) Review recent biochemistry (sodium, potassium, chloride, urea, creatinine, glucose) to look for
signs of dehydration, diabetes and electrolyte imbalances. Elevated urea and creatinine may give an
indication of severity of dehydration.

2) Acute dehydration greatly increases the risk of acute kidney injury (AKI) and should be managed quickly.

3) Haemoglobin/red blood cells counts may be elevated
in dehydration because the blood is more concentrated with water loss from the intravascular space.

4) Arterial blood gases and serum lactate should be measured to assess degree of acid/base balance and oxygenation of the tissues and can aid diagnosis of sepsis or diabetes or heart failure.
5) Magnesium, calcium and phosphate may fall in patients who are ill and should be replaced if required

Question 51

How may we determine if patient requires IV fluids at all ?

Answer 51

1) If hyperV, patient likely needs fluid restriction or gentle diuresis
2) If hypoV or EuV, allow patients to eat and drink IF POSSIBLE. If patient receives enough fluid through this or through this + another route (e.g. nasogastric route), then no IV fluids. If no receive enough then IV fluids.

Question 52

Identify 3 causes of hypomagnesaemia.

Answer 52

1) GI losses (diarrhea, small bowel bypass, chronic PPI use)
2) Alcoholism (inadequate intake and excessive renal excretion)
3) Renal losses (Gitelman syndrome, causes inappropriately high magnesium excretion)

Question 53

Identify therapeutic uses of Magnesium.

Answer 53

IV Magnesium:

• treats ventricular arrhythmias
• help in cases of acute severe asthma
• treatment of choice in eclampsia (a major cause of maternal mortality) and some cases of pre-eclampsia

Question 54

What are the four most abundant cations ?

Answer 54

Na+, K+, Ca2+, Mg2+

Question 55

Where in the body is Magnesium found ?

Answer 55

Muscle, soft tissue, and matrix of bone.

Question 56

Is Magnesium an intra or extracellular ion ?

Answer 56

Intracellular ion

Question 57

What is honeymoon cystitis?

Answer 57

“Honeymoon cystitis” is when cystitis follows frequent sexual intercourse; traditionally this
occurred on honeymoon.

Question 58

What are some causes of urethritis ?

Answer 58

Infection of the urethra (urethritis) is associated with
1) wearing tight clothing, using chemical irritants such as perfumed soap and in postmenopausal women with oestrogen deficient mucosa.
2) STIs and genital ‘self’ infections
-STIs that can present in this way are Chlamydia and Gonorrhoea, as well as Herpes Simplex and
Trichomonas

Question 59

Why may a pharmacist suggest drinking

cranberry juice following a UTI ?

Answer 59

From the SIGN guidelines, cranberry products have been shown to have a beneficial effect in preventing urinary recurrent infections in adult women.

Question 60

Why does my wee brother, who recently had a urinary infection, have to go to hospital for
special tests while my older sister was treated by our family doctor?

Answer 60

Unlike adults, urinary tract infections in children are often associated with underlying renal tract abnormalities which can be associated with recurrent infection and scarring of the kidneys. So it is good clinical practice to refer them for further investigations to clarify matters.

Question 61

Which components of a urine dipstick test may be different in a UTI ?

Answer 61

-Leucocytes are normally found in urine but excessive
numbers are not only present in infected urine

-Nitrites are indirect indicators of the presence of bacteria but only detect those bacteria that have the ability to reduce nitrates to nitrites eg E. coli (unlike staph which cannot)

Question 62

Why are mid-urine samples used ?

Answer 62

Mid-stream samples are used as they are the most reliable portion of the urine specimen:
both the first and the last part of the urine sample can be contaminated with debris and matter from
the urethra (early specimen) or the trigone of the bladder (the floor/base of bladder) or the prostate
gland (late sample).