EHR522 weeks 10-13

Renal Physiology

• The kidneys filter around 200 liters of fluid from the bloodstream daily, allowing toxins, metabolic wastes, and excess ions to leave the body in urine while returning needed substances to the blood.
• The kidneys maintain the body's internal environment by regulating water volume and solute concentration, ion concentrations, acid-base balance, and excreting metabolic wastes and foreign substances.
• They also produce erythropoietin and renin, important molecules for regulating red blood cell production and blood pressure, and convert vitamin D to its active form.

Kidneys – Location and External Anatomy

• The kidneys are bean-shaped and lie in a retroperitoneal position, extending from T12 to L3, with the right kidney slightly lower than the left.
• The ureter, renal blood vessels, lymphatics, and nerves join each kidney at the hilum and occupy the sinus.
• Each kidney has an adrenal gland atop it, an endocrine gland that is functionally unrelated to the kidney.

Renal Corpuscle

• The renal corpuscle consists of a glomerular capsule with parietal and visceral layers.
• The visceral layer clings to the glomerular capillaries and contains filtration slits, allowing filtrate to enter the capsule space.

Renal Tubule and Collecting Duct

• The renal tubule is approximately 3cm long and has three major parts: the proximal convoluted tubule, the nephron loop, and the distal convoluted tubule.
• The terms proximal and distal indicate the relationship of the convoluted tubules to the renal corpuscle.
• The meandering nature of the renal tubule increases its length and enhances its filtrate processing capabilities.

Classes of Nephrons

• Nephrons are divided into two major groups: cortical and juxtamedullary.
• Cortical nephrons (85% of nephrons) are located entirely in the cortex, while juxtamedullary nephrons originate close to the cortex-medulla junction and play a crucial role in producing concentrated urine.

Glomerular Filtration Rate (GFR)

• The huge surface area and high permeability of the filtration membrane explain how the relatively modest 10 mmHg NFP can produce large amounts of filtrate.
• The adult kidneys produce about 180L of filtrate daily, translating to a normal GFR of 120-125 mL/min.

Regulation of Glomerular Filtration

• GFR is tightly regulated to serve two crucial and sometimes opposing needs: maintaining extracellular homeostasis and maintaining blood pressure.
• Increased GFR increases urine output, reducing blood volume and blood pressure.

Reabsorptive Capabilities of the Renal Tubules and Collecting Ducts

• Aldosterone fine-tunes reabsorption of sodium in response to decreased blood volume or blood pressure, or high extracellular potassium concentration.
• Atrial Natriuretic Peptide (ANP) reduces blood sodium, decreasing blood volume and blood pressure.

Urine – Chemical Composition

• Water accounts for about 95% of urine volume, with the remaining 5% consisting of solutes.
• The largest component of urine by weight, apart from water, is urea, derived from the breakdown of amino acids.
• Other nitrogenous wastes in urine include uric acid, creatinine, and other solutes.
• Unusually high concentrations of any solute or the presence of abnormal substances may indicate pathology.

Urine Transport, Storage, and Elimination

• The ureters transport urine from the kidneys to the bladder.
• Urine is stored in the bladder until its release through the urethra is convenient, a process called micturition.

Pathophysiology of Chronic Kidney Disease (CKD)

• Mild renal insufficiency often has a normal or near-normal serum creatinine concentration.
• Homeostatic mechanisms permit the serum concentration of sodium, potassium, calcium, and phosphorus to remain within the normal range, especially in mild to moderate renal failure.
• Adaptive hyperfiltration, initially beneficial, results in long-term damage to glomeruli, manifesting as proteinuria and progression to renal failure.

Pathophysiology of CKD (continued)

• Gradual decline in renal function is initially asymptomatic, with the damaged kidney responding with higher filtration and excretion rates per nephron, masking symptoms until only 10-15% of renal function remains.
• Progressive renal failure causes loss of excretory and regulatory functions, leading to End-Stage Renal Disease (ESRD) and uraemic syndrome.
• Manifestations of the uraemic state include anorexia, nausea, vomiting, fatigue, pericarditis, peripheral neuropathy, and central nervous system abnormalities (ranging from loss of concentration to seizures, coma, and death).

Pathophysiology of CKD (continued)

• No direct correlation exists between the absolute serum levels of blood urea nitrogen (BUN) or creatinine and the development of these symptoms.
• Patients may present with peripheral oedema, pulmonary oedema, and congestive heart failure.
• To continue life, uraemic patients require Renal Replacement Therapy (RRT) using haemodialysis, peritoneal dialysis, or renal transplantation.
• The loss of the excretory function of the kidney results in the build-up of toxins in the blood, affecting cellular enzyme activities and inhibiting systems such as the sodium-potassium pump.

Pathophysiology of CKD (continued)

• The loss of the regulatory function of the kidneys results in the inability to regulate extracellular fluid volume and electrolyte concentrations, adversely affecting cardiovascular and cellular functions.
• Most patients with advanced CKD are volume overloaded, resulting in hypertension and often congestive heart failure.
• Other malfunctions in regulation include impaired generation of ammonia and hydrogen ion excess, resulting in metabolic acidosis and decreased production of erythropoietin, the primary reason for anaemia in ESRD patients.

Diagnostic Testing and Treatment

• The decision to begin dialysis is determined by factors including cardiovascular status, electrolyte levels, chronic fluid overload, severe and irreversible oliguria, anuria, significant uraemic symptoms, and abnormal laboratory values.
• RRT does not correct all signs and symptoms of uraemia and often results in other concerns and side effects.

Haemodialysis

• Haemodialysis is the most common form of RRT, with approximately 95% of all patients undergoing haemodialysis in a centre or at home.
• In other countries, some patients prefer home-based methods such as peritoneal dialysis.
• Haemodialysis is a process of ultrafiltration (fluid removal) and clearance of toxic solutes from the blood, necessitating vascular access by one of three methods: fistula, graft, or central venous catheter.

Haemodialysis (continued)

• Fistula is the most common access method, providing the best long-term vascular access and having the lowest risk of complications.
• Graft is an artificial tube placed in the arm or leg, allowing patients to travel and dialyse on their own schedules.
• Patients with cardiac instability may also be placed on peritoneal dialysis because this method does not involve the major fluid shifts experienced with haemodialysis.

Peritoneal Dialysis

• Complications of peritoneal dialysis are due to increased intra-abdominal pressure resulting from instillation of dialysate into the peritoneal cavity, including infection, hernias, low back pain, obesity, and gastroesophageal reflux.
• Patients may absorb as many as 1,200 kcal from the dialysate per day, contributing to the development of obesity and hypertriglyceridaemia.

Long-Term Complications of Dialysis

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Kidney Transplant

• Transplantation of kidneys is the preferred treatment of ESRD.
• The source of the kidneys available for transplant can be a living relative, an unrelated individual, or a cadaver.
• Because of the shortage of organs available for transplantation and improvements in immunosuppression medications, living non-related transplants are becoming more frequent.
• Following transplantation, patients are placed on immunosuppression medication, including combinations of glucocorticosteroids, calcineurin inhibitors, mTOR inhibitors, cell cycle inhibitors, costimulatory blockers, and induction agents.

Kidney Transplant (continued)

• New immunosuppression medications are constantly being developed, allowing for minimisation of side effects through alteration of therapies or combinations of therapies.

Research Data

• Among patients with CKD, researchers have shown that various exercise training interventions of 4-6 months are associated with marked improvements in cardiorespiratory fitness, reductions in markers of inflammation, and improvements in muscle strength.
• Resistance training programs lead to improvements in muscular strength in all stages of CKD.
• Changes in plasma lipids in response to exercise training seem to be attenuated in patients with CKD, and body composition changes are variable.

Research Data (continued)

• Other benefits associated with exercise training include a reduction in depression scores and improvements in health-related quality of life indices.
• Improvements in heart rate variability have also been reported, with a shift toward greater vagal tone following exercise training.
• In general, the findings of significant benefits from exercise training in CKD patients seem to be stronger in the ESRD population, possibly because most of the exercise studies to date have been done in this cohort.

Exercise Recommendations

• Patients with CKD who are not on dialysis have been shown to benefit from exercise training programs using standard exercise prescriptions for the general population, so long as the individuals are screened properly, start at a low to moderate intensity, and progress gradually.
• With regard to patients with ESRD, the timing of exercise in relation to the dialysis treatment should be considered.
• Exercising during treatment (intra-dialytic exercise) is recommended since it has significant physiologic benefit, enhances exercise compliance, and reduces the boredom associated with dialysis treatments.

Exercise Recommendations (continued)

• Exercising immediately before or after dialysis is generally not well tolerated and therefore not recommended.
• Research in haemodialysis patients demonstrates that larger adaptations usually occur when exercise is completed on non-dialysis days, but that intra-dialytic exercise is likely to produce better adherence rates.
• Exercise should be deferred if the patient is experiencing shortness of breath related to excess fluid status.

Exercise Recommendations (continued)

• Vigorous non-contact sports and activities are generally well tolerated by transplant recipients who have exercise trained to attain adequate muscle strength and cardiorespiratory endurance through a comprehensive conditioning program.
• Cardiorespiratory exercise should be prescribed 3-5 days/week as recommended for the general population.
• Resistance exercise should be performed 2-3 days/week.
• Flexibility exercises should be performed whenever CKD patients exercise train; however, because of the stiffness that patients with ESRD experience after prolonged periods of sitting in dialysis chairs, they should be encouraged to stretch daily.

Exercise Recommendations (continued)

• Cardiorespiratory exercise should be prescribed at a moderate to vigorous intensity (50-80% VO2 reserve) for patients with CKD who are not receiving dialysis.
• In patients with ESRD, exercise intensity should be guided by RPE, because heart rates are highly variable in this patient population as a result of fluid shifts and vascular adaptations to fluid loss during the dialysis treatment.
• Many ESRD patients may initially tolerate only a few minutes of very low-level exercise, which means that any formal warm-up and cool-down intensities are less relevant.

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Types of Mental Illness

• Psychotic disorders:
  • Characterized by abnormal thinking and perceptions
  • Examples: Schizophrenia, Schizoaffective Disorder
• Mood disorders:
  • Characterized by disturbances in emotional state
  • Examples: Major Depressive Disorder, Bipolar Disorder
• Trauma- and stressor-related disorders:
  • Characterized by anxiety and fear responses to traumatic events
  • Examples: Post-Traumatic Stress Disorder (PTSD), Acute Stress Disorder
• Anxiety disorders:
  • Characterized by excessive worry and fear
  • Examples: Generalized Anxiety Disorder, Panic Disorder, Phobias
• Feeding and eating disorders:
  • Characterized by disturbances in eating patterns
  • Examples: Anorexia Nervosa, Binge-Eating Disorder

Schizophrenia

• Characterized by disruptions in thinking, acting, and expressing emotions
• Affects about 1% of the Australian population
• More common in males than females
• Can be caused by genetic susceptibility and environmental influences

Diagnosis of Schizophrenia

• Requires at least two symptoms present for at least one month
• Symptoms include:
  • Delusions
  • Hallucinations
  • Disorganised thinking or speech
  • Disorganised or abnormal motor behaviour
  • Negative symptoms
• Must have significant impact on daily functioning

Symptoms of Schizophrenia

• Positive symptoms:
  • Added thoughts or actions not based in reality
  • Examples: delusions, hallucinations, disorganised speech
• Negative symptoms:
  • Lack of normal thinking or behaviors
  • Examples: lack of interest, social withdrawal, diminished emotional expression
• Cognitive symptoms:
  • Impairment in executive and cognitive function
• Mood symptoms:
  • Abnormal emotional states
  • Examples: depression, anxiety

Management of Schizophrenia

• Goal is to ease symptoms and reduce risk of relapse
• Treatments include:
  • Medications: antipsychotics
  • Psychotherapy: addressing behavioral, psychological, social, and occupational problems
  • Hospitalisation: for severe symptoms or risk of harm to self or others
  • Electroconvulsive therapy: for severe depression or catatonia

Major Depressive Disorder (MDD)

• Characterized by sad, empty, or irritable mood
• Accompanied by changes that significantly affect daily functioning
• Affects about 10% of the Australian population
• Slightly more common in females than males

Diagnosis of MDD

• Must experience at least five symptoms for two weeks
• Symptoms include:
  • Depressed mood
  • Loss of interest or pleasure in activities
  • Changes in appetite or sleep
  • Fatigue or loss of energy
  • Feelings of worthlessness or guilt
  • Difficulty concentrating or making decisions
  • Recurring thoughts of death or suicide

Aetiology of MDD

• Complex mental illness involving genetic, environmental, and psychosocial factors
• Risk factors include:
  • Abuse
  • Age
  • Chronic disease or illness
  • Conflict
  • Death or loss
  • Family history
  • Gender
  • Major events
  • Stress
  • Substance misuse

Management of MDD

• Range of management strategies available
• Includes:
  • Pharmacological interventions: SSRIs, SNRIs
  • Exercise interventions
  • Psychotherapy: addressing behavioral, psychological, social, and occupational problems
  • Transcranial magnetic stimulation
  • Electroconvulsive therapy

Post-Traumatic Stress Disorder (PTSD)

• Characterized by intense and disturbing thoughts and feelings
• Typically caused by exposure to traumatic event
• Symptoms usually occur within three months of exposure
• Affects about 12% of the Australian population
• Women are twice as likely as men to be diagnosed with PTSD

Diagnosis of PTSD

• Must experience symptoms for at least one month
• Symptoms include:
  • Intrusive thoughts or memories
  • Avoidance of stimuli associated with trauma
  • Cognitive and mood changes
  • Physical and emotional reactions
• Symptoms must significantly interfere with daily functioning

Aetiology of PTSD

• Multifactorial, involving genetic, environmental, and psychosocial factors
• Risk factors include:
  • Exposure to traumatic events
  • Occupations related to traumatic events
  • Pre-existing mental illnesses or family history of mental illness
  • Substance misuse/abuse
  • Limited support systems
  • Family history of PTSD

Management of PTSD

• Range of management strategies available

• Includes:

  • Trauma-focused therapy
  • Cognitive processing therapy
  • Prolonged exposure therapy
  • Medications: SSRIs, SNRIs### Exercise in MDD Treatment

• Supervised exercise programs by professionals are more successful

• Exercise is as effective as SSRIs in treating MDD

• Over the long-term (6 months), exercise is more effective than SSRIs in achieving MDD remission

• Most studies focus on aerobic exercise, but resistance training also improves MDD symptoms

• Lifestyle factors like dietary modification, smoking cessation, and sleep hygiene can act additively or synergistically with exercise to improve MDD symptoms

Biological and Psychological Mechanisms

• Exercise reduces depression through biological and psychological mechanisms
• Exercise can retard mechanistic pathways responsible for MDD development
• There is a dose-response relationship between exercise volume and reduction in MDD risk/symptoms
• The greatest differences in MDD risk are seen between sedentary and low-dose physical activity

Exercise Participation and Adherence

• Exercise participation and adherence are lower in MDD patients
• Strategies like motivational interviewing, action planning, and goal setting can optimize adherence

Exercise in Anxiety Disorders

• Fewer RCTs have been performed to investigate the effect of exercise on anxiety
• Research in anxiety has heavily favored aerobic exercise, with little on resistance training
• Aerobic exercise is effective in reducing symptoms in those with diagnosed anxiety disorders and those with raised anxiety
• Higher intensity aerobic exercise is more effective than lower intensity exercise

Physiological Mechanisms in Anxiety

• Physiological mechanisms hypothesized to be responsible for exercise benefits in anxiety overlap with those proposed for MDD
• These mechanisms include alterations in serotonergic and noradrenergic pathways, increased 5-hydroxytriptamine turnover, and increased atrial natriuretic peptide levels

Overcoming Anxiety Sensitivity

• Exposure to exercise provokes anxious feelings in some individuals, but increases tolerance and decreases anxiety sensitivity
• Exercise increases self-efficacy as patients see an increase in their ability to cope with physiological challenges
• Engagement in exercise can lead to increased social interaction and distraction from anxious rumination

The Impact of Severe Mental Illness

• People with Schizophrenia have a reduced life expectancy of 15-25 years compared to the general population, mainly due to cardiometabolic sequelae.
• This reduction in life expectancy increases to 25-30 years when drug or alcohol abuse/misuse is combined with a Schizophrenia diagnosis.
• Severe mental illness also results in a dramatic reduction in quality of life, leading to a significant non-fatal burden.

Exercise in Schizophrenia Treatment

• People with Schizophrenia typically have reduced levels of physical activity and lower levels of aerobic fitness.
• Barriers to exercise in Schizophrenia patients include fatigue, low motivation, lack of confidence, anxiety, and lack of resources and encouragement.
• Exercise can improve aerobic fitness and reduce cardiometabolic risk factors in people with Schizophrenia.
• Moderate-to-vigorous aerobic exercise of 90 minutes per week can reduce psychiatric symptoms, including positive, negative, cognitive, and mood symptoms.

Exercise in PTSD Treatment

• There is limited data on the effect of exercise on PTSD symptoms, but exercise has been shown to have a positive impact.
• There appears to be a dose-response relationship between exercise and PTSD symptoms, but the optimal exercise type, dose, and duration are unclear.

General Exercise Progression and Regression Principles for Mental Illness

• Practical recommendations for exercise in mental illness include limiting competition, encouraging self-selection, focusing on moderate intensity, and avoiding overtraining.
• It is essential to consider individual differences and unique situations when prescribing exercise for mental illness.

Healthcare Services and Providers

• General Practitioners (GPs) are the primary point of contact for mental health services, with 13% of all GP encounters related to mental illness.
• Community Mental Health Care Services provide a range of services, including housing, support groups, and access to other medical services.
• In-Patient Hospital Care is available for people who require acute hospitalization due to mental illness.
• Residential Care provides specialized mental health care in a domestic-like environment for a small percentage of people with mental illness.

Outcome Measures in Mental Illness

• A range of questionnaires, such as the PHQ-9, Beck Depression Inventory (BDI), and Centre for Epidemiological Studies – Depression Scale (CES-D), are used to characterise the severity of mental illness.
• The DASS-21 is a commonly used scale that assesses depression, anxiety, and stress.

Social Stigma and Discrimination

• Social stigma and shame reduce the likelihood of people seeking treatment for mental illness.
• Different cultures have varying perspectives on mental illness, and unhelpful views include the perception that people with mental illness need to take ownership of their condition.

Violence and Mental Illness

• The major determinants of violence are sociodemographic and socioeconomic factors, such as being young, male, and of low socioeconomic status.
• Substance abuse is also a significant determinant of violence.

Positive Interaction and Communication

• Building relationships, communicating effectively, and involving families and carers are essential for positive interaction and communication in mental health care.
• Strategies for de-escalation include listening, offering reflective comments, waiting until the person has expressed their frustration, and expressing empathy and concern.