Pathophysiology Of Acute Renal Failure Biology Essay

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The following pages will concern the scenario of Georgina Lawson. I will examine the pathophysiology of Acute Renal Failure and then highlight the pharmacological management specific to Mrs Lawson's treatment. I will then concentrate specifically on Mrs Lawson's condition by identifying three signs and symptoms that she displayed upon admission, and discuss how the diagnosis of Acute Renal Failure has been reached. Next there will be a discussion on the tests undertaken at the time of Mrs Lawson's admission, their relevance, results and also the expected findings when the assumption of Acute Renal Failure has already been made. Additional tests that could also been ordered but weren't will also be highlighted with their potential benefits shown.

In the last part of this paper, I will write about the impact of having a BMI of 50 on the disease of process of T2DM and Acute Renal Failure as well as the pharmacological implications of having such a weight.

Part 1

Acute renal failure is a representation of the rapid decline in renal function whereby blood nitrogenous wastes (urea nitrogen, uric acid, and creatinine) accumulate due to a decreased glomerular filtration rate, impairing fluid and electrolyte balances.reference? Filtration of plasma through the glomerular capillaries into the Bowman's space is the initial stage of urine production.reference Large molecules can not easily cross through the glomerular wall during normal production therefore urine is protein free. The capillary filtration pressure is higher in the glomerular than in other capillaries in the body; this increased area of pressure is what allows for the afferent and efferent contraction and relaxation of arterioles to produce high volumes of filtrate. If the glomerular filtration rate is altered the initial stage of urine production does not occur, therefore diminishing the kidney's ability to remove nitrogenous waste from the body (Porth, 2005, p.?).

Acute Renal Failure is categorised in 3 areas, prerenal, intrinsic and postrenal. As prerenal characterises the symptoms displayed by Georgina Lawson only that area will be discussed. Possibly intrinsic if going down the line of Glomerulonephritis.

3 Symptoms:

BP on admission 160/80

Hypertension is a constant increase of resting systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg or both.reference Primary hypertension with no known cause is most common where as secondary hypertension with an identified cause is usually due to a renal disorder. referenceUsually, no symptoms develop unless hypertension is severe or long-standing (Bakris G, 2010). Blood flow depends on the rate of heart beats and the volume of blood pumped out with each beat. If rate or volume increases, blood pressure rises, and prolonged hypertension may damage many organsreference. Initially the heart works harder to pump out more blood against higher resistance.reference The heart then requires more oxygen, and is more susceptible to damage, also predisposing arteries and arterioles to damage. Arteriosclerosis results when blood moves through arteries and arterioles at high pressure, damaging the vessel causing white blood cells to be drawn to the damaged area to form a plaque.reference Prolonged hypertension causes the kidneys to be damaged as the delicate capillaries of the kidney are continually exposed to high blood pressure, they break down, becoming permeable to proteins and other molecules. Tubules can become clogged, decreasing the kidney's ability to make urine. The presence of protein injures capillaries cell wall membranes causing further damage and worsening the situation (Porth, 2005,p.?).

Dark, cloudy, odorous urine

Protein is present due to damage to capillary cell walls in the kidneys, which allow proteins to pass through pores in the basement membrane during glomerular filtration. Reference Normally red blood cells and plasma proteins do not pass through the glomerulus; therefore urine is a blood and protein-free filtrate. In a healthy person the glomerular filtration barrier will excrete less than 150mg of protein in the urine over a 24hr period (Porth, 2005, p.?).

Georgina described to the GP low urine output with burning on passing urine, followed by a fluid increase. On admission urine output is still minimal, concentrated with a strong odour.Why do you think this is happening?

Cloudy or murky urine is a sign of infection, which may also have an offensive smell. Reference Murky urine may also be caused by the presence of bacteria, mucus, white blood cells or red blood cells, epithelial cells, fat, or phosphates.reference

Osmolality or specific gravity of urine changes with the concentration of solutes, depicting a sliding scale of the hydration status and functionality of the kidneys.reference The ability to concentrate urine is lessened when renal function in impaired, with specific gravity values falling to 1.006- 1.010, while normal values during times of hydration are 1.030- 1.040. What was Georgina's result and what does this demonstrate?

Pitting Oedema bilaterally

Edema is the expansion of the interstitial fluid volume by 2.5-3L which is evident by palpable swelling where?. Edema manifestations associated with Georgina's sudden onset of symptoms include; Increased capillary filtration pressure: An increase of extracellular volume is caused by the decrease of sodium and water excretion by the kidneys, increases of capillary volume, pressure and consequent movement of fluid into the tissue space.reference

Deceased capillary colloidal osmotic pressure: caused by inadequate production or abnormal loss of plasma proteins, largely albumin, most commonly in the kidney. This is due to the glomerular capillaries becoming permeable to plasma proteins, predominantly albumin, allowing them to be filtered out of the blood and lost through urine.reference

Increased capillary permeability; enlargement of capillary pores or integrity of capillary walls are damaged, causing permeability is increased. This allows plasma proteins and other osmotically active particles to move into the interstitial space and increase colloid osmotic pressure, in so doing enabling the accumulation of interstitial fluid. (Porth, 2005, p?)

Part 2

Discuss the tests that were ordered for Georgina and explain why they were chosen in regards to your chosen element discussed in part 1.

Bloods:

Na+: 135 Sodium: 135- 145

K+: 5.5 Potassium: 3.2- 4.3

Cl: 108 Chloride 99 - 109

Urea: 12.0 3.0- 8.0

Creatinine: 1.5 mg/dl 45- 90

Cholesterol: 6 <5.5

WBC: 8 4.0- 11.0

Hb: 105 115- 160

Platelets: 170 150-450

Hbalc: 7%

Glucose: 8.7 3.0- 6.0

Total Protein: 95 65- 80

Discuss any results that were given and what they add to the diagnosis/element that you chose to discuss.

Acute renal failure characterized by three common findings: reduced creatinine clearance, excessive accumulation of nitrogen compounds in the blood known as Azotemia, and hyperkalemia .reference Creatinine is a waste product of muscle metabolism and filtered freely by glomeruli without reabsorption causing levels to increase when glomerular filtration is reduced. Routinely measured are creatinine, urea, and uric acid collectively known as Azotemia. Individually urea and uric acid are not indicative of renal failure, however levels do rise when there is a reduction in the glomerular filtration rate. Ratios between urea and creatinine to determine lack renal function. Urea levels are expressed as the concentration of nitrogen derived from urea, called the BUN, which are hydrolysed to form ammonia and carbon dioxide. Urea is freely filtered by the glomerulus with re absorption increasing due to a reduce blood flow through the tubules. Glomerular filtration is reduced because of insufficient blood flow to the glomeruli, allowing for amplified retention of nitrogenous waste products. Reduced renal blood flow also promotes ADH secreation facilitating reabsorption of water and urea, which gives reason for the ratio of creatinine to urea in pre renal failure.

Potassium is secreted by the collecting tubule in response to aldosterone and is filtered by the glomerulus and partially reabsorbed in the proximal tubule.reference When insufficient blood flow occurs, potassium is not filtered adequately and when tubules are damaged, potassium levels climb because the movement between potassium and sodium is impaired.reference Sodium levels of urine decline in prerenal failure, as it is maintained to promote increased blood flow. Where as urine sodium levels increase in renal failure due to tubule failure. Tests that are often irregular with renal failure are protein, blood, leukocytes, and specific gravityreference.

Glomerular damage allows albumin and red blood cells to pass through the basement membrane and enter the filtrate, while leukocytes move to the site of damage entering the filtrate through glomerular lesions and passing between tubular cells. Tubular failure hinders the kidneys ability to regulate the concentration gradient causing the urine produced to be consistently of the same specific gravity as the plasma (1.010). Because a high percentage of diabetics develop co morbidities of renal and vascular disease glucose and pH are also useful what?, as renal failure results in acidosis with concomitant failure to acidify the urine.

So what tests were done? This is a good discussion of what we are looking for in her bloods but what else was done to diagnose her condition? Where the results what would be expected in Georgina's case? Why was her Hb low?

A useful test that could have been utilised to investigate Georgina's renal dysfunction is a kidney radionuclide scan, or kidney scan. A small amount of radionuclide, also known as radioactive dye is injected into the body in order for diagnostic imaging of the kidneys with a gamma camera to be under taken to obtain images that are significant in identifying specific areas of damage to determine treatments of various kidney diseases and conditions (Phillips J, 2002).

Part 3

Ensure that you relate everything back to Georgina.

Diltiazem Hydrochloride

What is the above medication?

How does it work?

How does it achieve its therapeutic effect?

A calcium channel blocker that inhibits calcium ion influx across cardiac and smooth-muscle cells during membrane depolarization, decreasing myocardial contractility and oxygen demand. Reference Also dilates coronary arteries and arterioles.

The therapeutic benefits of diltiazem in supraventricular tachycardias are related to its ability to slow AV nodal conduction time and prolong AV nodal refractoriness. It has effects on AV nodal conduction that it is thought to selectively reduce the heart rate during tachycardias involving the AV node with minimal effect on normal AV nodal conduction at normal heart rates.reference

Therapeutic use?

Or indication for use?

What about for your patient?

Angina, Hypertension, Atrial Fibrillation or Atrial Flutter, Paroxysmal Supraventricular Tachycardia.

Georgina has a history of hypertension managed by 180mg daily. reference

What is the therapeutic range for this medication?

Therapeutic blood levels appear to be in the range of 40 - 200 mg/mLreference

Side effects?

Headache, dizziness, edema, nausea, hepatic injury, rash. reference

Drug interactions.

Pharmacokinetics A:

D:

M:

E:

HL:

P:

Well absorbed from the gastrointestinal tract, and subject to an extensive first-pass effect.

The apparent volume of distribution of diltiazem is approximately 305 L

Liver

Kidneys and bile

Plasma elimination half-life is approximately 3.4 hours.

2-3hrs, onset 30 min

Medication critique

240 to 360 mg daily is the average dosing for hypertention, where as Georgina is prescribe 180 mg daily. Revision of dosing may be required to achieve desired anti hypertensive effect once other fluid and renal issues have been resolved.

Where did you get this information from? Where are your references?

Cartia (Aspirin)

What is the above medication?

How does it work?

How does it achieve its therapeutic effect?

Analgesic and anti inflammatory effects by blocking prostaglandin synthesis. Low doses delay clotting by blocking prostaglandin synthesis stops the formation of platelet aggregating substance thromboxane A2

Therapeutic use?

Or indication for use?

What about for your patient?

Aspirin is often given as a prophylaxis to prevent cardiac events due to its anti platelet and vasodilatation effects.

Special care is needed in patients with renal and/or hepatic impairment as excretion occurs in the kidneys. Georgina also has traces of blood in her urine specimen, therefore an anti platelet should be avoided so as to allow for platelet aggregation at the site of injury.

What is the therapeutic range for this medication?

10 to 20 mg/dL

Side effects?

Use has been shown to increase the risk of gastrointestinal bleeding.

Drug interactions

Aspirin is know to interact with sulfonylurea, Glibenclamide is a second generation derivative of this drug, therefore its anti hyperglycaemic effects may be hindered.

Pharmacokinetics A:

D:

M:

E:

HL:

P:

Aspirin is released from Cartia tablets when the pH is >6, this occurs in the duodenum and small intestine.

Highly bound to plasma protein, especially albumin

Mainly in the gastrointestinal mucosa and the liver

Largely excreted by the kidneys.

2- 4.5hrs

1- 2hrs

Medication critique

With the fluid overload and lack of urination Goergina is experiencing, aspirin would not have an effect on her current hypertensive. Although some studies have discussed that the vasodilatory effects of aspirin would out weight the negative anti platelet effects on patients with kidney diseases, standard treatments remain that those suffering renal failure and cardiovascular disease should not be routinely prescribed aspirin.

Glibenclamide

What is the above medication?

How does it work?

How does it achieve its therapeutic effect?

Oral hypoglycaemic

Appears to lower the blood glucose acutely in individuals with type 2 diabetes by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells.

Therapeutic use?

Or indication for use?

What about for your patient?

It acts with glucose to improved sensitivity of beta cells to physiological glucose stimulus and leads to an insulin secretion in the rhythm of meals.

Increased bgls will be lowered by this and help stimulate Georgina's pancreas to improve beta cell production?????

What is the therapeutic range for this medication?

Side effects?

Hypoglycaemia may occur. Gastrointestinal effects such as nausea, vomiting, epigastric fullness and diarrhoea are the most common side effects.  

Drug interactions.

Drugs which may enhance the hypoglycaemic action should be used with caution.

Pharmacokinetics A:

D:

M:

E:

HL:

P:

Nearly completely absorbed (84 +/- 9%) after oral administration.

Is extensively bound (99%) to serum proteins.

Completely metabolised in the liver.

Excreted as metabolites in the bile and urine, approximately 50% by each route.

2-5 hours after oral administration.

Peak serum concentration is reached in two to six hours

Medication critique

In patients with renal insufficiency, depending on the degree of the renal excretion disorder, there is increased elimination of the metabolites via the bile. If Georgina's kidney dysfunction is significant she should be continued on this medication.

References??

Metformin

What is the above medication?

How does it work?

How does it achieve its therapeutic effect?

Metformin causes increased peripheral uptake of glucose by increasing effectiveness of available exogenous or endogenous insulin.reference

The mode of action of metformin may be linked to increased insulin sensitivity. It does not stimulate insulin release but does cause antihyperglycaemic effects when insulin is present. Possible mechanisms of action include inhibition of gluconeogenesis in the liver, delayed glucose absorption in the gastrointestinal tract and increased peripheral uptake of glucose.reference

Therapeutic use?

Or indication for use?

What about for your patient?

Metformin has antiketogenic activity comparable to some extent, to insulin itself. Metformin lowers both basal and postprandial blood glucose in diabetic patients but does not cause hypoglycaemia in either diabetic or normal individuals.

reference

What is the therapeutic range for this medication?

500 mg three times a day is often sufficient to obtain diabetic control, the dose can be increased to 1 g three times daily, which is the maximum recommended daily dose.reference

Side effects?

Mild gastrointestinal symptoms such as diarrhoea, nausea, vomiting, abdominal pain and loss of appetite are very common, especially during the initial treatment period. These symptoms are generally resolve during continued treatment.reference

Drug interactions.

Calcium channel blockers may affect glucose control in diabetic patients therefore regular monitoring of glycaemic control is recommended.reference

Pharmacokinetics A:

D:

M:

E:

HL:

P:

Oral administration is absorbed along the entire gastrointestinal mucosa.

not bound to plasma proteins.

Excreted unchanged in the urine and does not undergo hepatic metabolism.

6hrreference

Medication critique

In patients with decreased renal function based on measured creatinine clearance, the plasma half-life of metformin is prolonged and renal clearance is decreased in proportion to the decrease in creatinine clearance. (Renal failure or renal dysfunction (creatinine clearance <60 mL/minute).reference

Key:

A: Absorption, E: Excretion, D: Distribution, M: Metabolism, HL: Half Life, P: Peak

Part 4

Choose one aspect/element of Georgina's case and discuss/analyse/explain in detail.

Why is Georgina commenced on a 600 ml fluid restriction.

Type 2 diabetes is characterized by peripheral insulin resistance with an insulin-secretory defect that varies in severity. For type 2 diabetes mellitus to develop, both defects must exist; overweight individuals have insulin resistance although only those with an inability to increase beta-cell production of insulin develop diabetes. In the progression from normal glucose tolerance to abnormal glucose tolerance, postprandial glucose levels initially increase, ultimately leading to the development of fasting hyperglycemia as inhibition of hepatic gluconeogenesis declines. Chronically elevated blood pressure contributes to the decline in renal function, hypertensive patients with diabetes must be referred for long-term management of the blood pressure. Antihypertensive therapy such as an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) should have been recommended to Mrs Lawson due to the decrease of proteinuria and slow decline in renal function independent of the effect on blood pressure. ACE inhibitors and ARBs tend to increase the serum potassium level, therefore should be used with caution in patients with renal insufficiency or elevated serum potassium levels (Votey, 2010). This decline in renal function and continal increase in blood pressure is caused due to an increased isotonic fluid retention; Fluid volume excess, or hypervolemia, occurs from an increase in total body sodium content and an increase in total body water. This fluid excess usually results from compromised regulating mechanisms of sodium and water as with congestive heart failure, kidney failure, and liver failure. It may also be caused by excessive intake of sodium from foods, intravenous solutions, medications, or diagnostic contrast dyes. The therapeutic goal is to treat the underlying disorder and return the extracellular fluid compartment to normal. Treatment consists of fluid and sodium restriction, and the use of diuretics. For acute cases dialysis may be required, although Georgina is not yet at this stage. Defining characteristics displayed include weight gain, edema, bounding pulses, shortness of breath; orthopnea, abnormal breath sounds: crackles/ rales, third heart sounds, intake greater than output, decreased hemoglobin or hematocrit, increased blood pressure, oliguria, specific gravity changes, azotemia, change in electrolytes, restlessness and anxiety (Porth, 2005, Unit 8).

Part 5

Professorial question

How would Georgina's pathophysiology and pharmacology be different if her BMI was 50? Please discuss what advise you would give Georgina about a new medication regime

Conventional pharmacokinetic parameters such as volume of distribution (Vd), clearance (Cl) and protein binding can change for some drugs in morbidly obese patients.reference Extensively lipophilic substances such as barbiturates and benzodiazepines show considerable increases in Vd for obese individuals.reference Less lipophilic compounds have displayed little or no change in Vd with obesity. There are however some exceptions to this rule such as Remifentanil, which is a highly lipophilic but displays no significant change in distribution in obese individuals. referenceConsequently, the absolute Vd remains somewhat unchanged and the dosage should be calculated on the basis of ideal body weight (Baerdemaeker, Mortier, 2005).

Due to the physiologic changes that occur in obesity, there are particular changes that occur in the pharmacokinetic processes. These physiological changes include distribution, where there is a higher percentage of body fat and lower percentage of lean muscle and body water reference?. Metabolism, where there is higher cardiac output and liver blood flow as well as an enlarged liver with altered histological status. Excretion, as there is higher renal blood flow and increased glomerular filtration rate. What this translates to in regard to pharmacokinetics of the obese person, is that distribution is altered due to tissue perfusion, tissue size, binding of drug to plasma proteins, and permeability of tissue membrane.

The volume of distribution of a substance is significantly impacted upon by obesity with particular significance associated with the lipid solubility of a drug. Protein binding of a drug may be transformed due to the changes in albumin, x1 acid glycoprotein and lipoproteins, although there is no steady rule that has been confirmed as yet reference. There has however, been signs of the clinical significance of lipoprotein bound drugs and their affinity to bind to tissue related to a lack of lean muscle mass. Effects of obesity on hepatic metabolism are not greatly understood, although specific enzymatic studies have been undertaken, with knowledge and understanding being associated to specific drugs rather than related to a formula related to the process of drug metabolism effects in the obsess. References?

With a BMI of such a scale it would need to be highlight to Mrs Lawson the importance of strict adherence to her prescribed medication regime as outlined by the multi disciplinary team involved in her case. It could be of benefit to explain the effects her high level adipose tissue has in relation to medication metabolisation and its association with losing weight.

Conclusion:

This assignment was centred on the health concerns presented in the scenario given for Georgina Lawson. Initially Acute Renal Failure was discussed with the pathophysiological consequences of the condition highlighted which also indicated the potential expected results should testing be undertaken. Next to be discussed was 3 of the symptoms that Mrs Lawson presented with upon admission. Mrs Lawson's blood pressure, urine status, and her pitting oedema were highlighted and related back to the onset of acute renal failure. The next section was concerned with the tests undertaken that assisted in the formation of an Acute Renal Disease diagnosis. Mrs Lawson's specific results were discussed as well as atypical results that would be expected to be found from a patient suffering from Acute Renal Disease. Medications that Mrs Lawson is currently taking was then analysed with their roles and intended effects of each medication included as well as their individual pharmacokinetics and pharmacodynamics. A general introduction to Type 2 Diabetes was discussed next with its relationship to Acute Renal Disease highlighted. In the last section, a hypothosis was investigated about the effects that an increase in BMI to a level of 50 would incur and the pharmacological changes that would be required to ensure successful treatment under this health condition.

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