Week 6/7 - Renal Disorders

Explain what the body does in response to a urinary tract obstruction

Dilation of the affected area in order to resume normal flow

Differentiate between the 2 types of urinary tract obstructions

• Upper - obstruction in the kidney or ureter

• Lower - obstruction in the bladder or urethra

Differentiate between hydroureter and hydronephrosis

• Hydroureter - dilation of the ureter to urine accumulation from an obstruction

• Hydronephrosis - dilation and swelling of the renal pelvis and calyces due to urine accumulation from an obstruction

Explain the pathophysiology of hydronephrosis

• An obstruction such as renal calculi or a tumour impede urine flow that refluxes back into the renal pelvis

• Eventually pressure increases and forces urine into renal tubules causing atrophy and therefore impairing tubular reasborption and excretion.

• Eventually urine accumulates in glomerulus and pressure causes atrophy and therefore reducing GFR.

Explain a neurogenic bladder and how it can cause a lower urinary tract obstruction.

A neurological disorder such as a stroke that alters bladder function and leads to an obstruction.

Explain how prostate enlargement can cause a lower urinary tract obstruction

Enlargement of the prostate which wraps around the urethra can cause compression and therefore obstruction.

Explain why flank pain is a symptom of a urinary tract obstruction

The obstruction causes urine accumulation in the kidneys and therefore swelling and dilation that stretches renal tissue and nerves in the renal capsule causing pain on the side of the affected kidney.

Explain why infection and fever are symptoms of a urinary tract obstruction

Normal urine flow typically flushes bacteria out of the urinary tract however the obstruction impedes flow, allowing bacteria to more easily enter the system and cause infection. As a response to infection the body increases its temperature to create an environment unfavourable to bacterial multiplication.

Explain why flank pain is a symptom of a urinary tract obstruction

The obstruction causes urine accumulation in the kidneys which leads to dilation and swelling. This stretches renal tissue and nerves in the renal capsule that send pain signals to the brain that can also trigger the brains vomiting centre.

Explain why increased urgency and frequency of urination as well as nocturia are symptom of a urinary tract obstruction

A lower urinary tract obstruction causes the detrusor muscle of the bladder to thicken in order to expel urine past the obstruction. This increasing thickness reduces the space available in the bladder to store urine. Additionally, the increased thickness leads to stiffness and involuntary spasms and contractions. These factors increase the urgency and frequency of urination, especially at night time.

Explain why haematuria is a symptom of a urinary tract obstruction

Obstructions lead to urine accumulation and increased pressure that damages blood vessels causing blood to leak into the urinary tract and come out in urine.

Differentiate between the 3 types of renal calculi

• Calcium - excess calcium combines with oxalate or phosphate that harden and form stones

• Struvite - occurs with bacterial infections in which a bacterial enzyme breaks down urea into ammonia making urine very alkaline, creating a favourable environment for stone formation

• Uric acid - occurs with excessive uric acid due to conditions such as gout and leukemia.

State the alternative name for renal cell carcinoma (RCC)

Hypernephroma

Explain the pathophysiology of RCC

A mutation in that inactivates tumour suppressor genes or activates protoncogenes of renal epithelial cells causes uncontrolled cell proliferation leading to tumour formation.

Differentiate between the 4 stages of RCC

1. Tumour < 7cm diameter and remains in the kidneys

2. Tumour > 7cm diameter and remains in the kidneys

3. Tumour extends beyond the renal capsule and spread to blood vessels and/or adrenal gland

4. Tumour extends beyond Gerota’s fascia and has spread to blood vessels, lymph nodes and other organs.

Explain Gerota’s fascia

A layer of dense connective tissue that wraps around the kidneys and adrenal glands.

Explain paraneoplastic syndrome

Symptoms caused by a tumour releasing hormones and other substances that trigger responses in other parts of the body rather than from damage from the tumour itself.

Explain why polycythemia can be a symptom of RCC

Paraneoplastic syndrome occurs in which the tumour releases erythropoietin causing increased RBC counts.

Explain why hypercalcaemia can be a symptom of RCC

Paraneoplastic syndrome occurs in which the tumour releases PTH-like peptide causing increased osteoclastic activity, renal tubular reabsorption of calcium and dietary absorption of calcium to increase serum calcium levels.

Explain why hypertension can be a symptom of RCC

Paraneoplastic syndrome occurs in which the tumour releases reinin, activating the RAAS to increase blood pressure.

Additionally, the tumour can compress on the renal artery and glomerular capillaries that detect this slowed blood flow and release renin to activate the RAAS to increase blood pressure.

Explain why feminisation or masculinisation can be symptoms of RCC

Paraneoplastic syndrome occurs in which the tumour can release sex hormones such oestrogens and androgens such as testosterone that lead to manifestation of female or male-reproductive related features and symptoms.

Explain why Cushing’s disease can be a symptom of RCC

Paraneoplastic syndrome occurs in which the tumour can release glucocorticoids such as cortisol, leading to excessive cortisol levels that cause Cushing’s Syndrome.

Explain how ischaemia leads to ATN

• Tubular cells are very metabolically active and have high oxygen requirements

• Reduced blood flow causes ischaemic necrosis

Explain how nephrotoxic substances lead to ATN

• Toxic substances such as constrast agents, drugs and heavy metals are poisonous to the kidneys

• Due to their high surface area they are highly absorptive and therefore more sensitive

Explain the pathophysiology of ATN

• Initiation - injury to epithelial cells due to ischaemia or nephrotoxicity causing reduced GFR and tubular filtration that leads to protein casts formation and increased serum creatinine and blood urea nitrogen (BUN)

• Maintenance - sustained reduction in GFR causes a continuing rise of serum creatinine and urea.

• Recovery - surviving epithelial cells begin to proliferate and differentiate in which GFR and filtration improves and serum creatinine and nitrogen begin to decrease.

Explain protein casts in ATN

When epithelial cells die and shed off basement membrane into the lumen of tubules, forming protein casts that obstruct.

Explain why oligoria is a symptom of ATN

Damaged epithelial cells reduce filtration function in which serum creatinine and urea increase. This reduces osmotic forces that draws water out of blood excreting into urine, decreasing urine volume.

Explain why azotaemia is a symptom of ATN

Damaged epithelial cells reduce filtration function in which serum creatinine and urea levels are severely high.

Explain why metabolic acidosis is a symptom of ATN

Damaged epithelial cells reduce filtration function, causing electrolyte imbalances and increased acid levels in the blood leading to metabolic acidosis.

Explain the normal defences of the urinary tract that protect from infection

• Bladder wall is coated with antimicrobial peptides

• The periurethreal and prostate glands produce antibacterial secretions

• Urinating flushes out the system

• Urine is acidic and contains antibodies and other properties that create an unfavourable environment for bacte

Explain why pregnancy increases chances of UTI

• Increased progesterone relaxes muscle. This dilates ureters, slowing down urine flow as well as decreases muscle tone of the bladder which increases chances of reflux

• Foetus places pressure and can compress on ureters that interfere fill urine flow.

Explain why menopause increases chances of UTI

Drop in oestrogen:

• Causes thinning of vagina and walls of urinary tract, increasing vulnerability to infection

• Decreases antibodies and immune factor formation

• Decreases growth of beneficial bacteria

Explain why prostate enlargement, renal calculi or tumours increase chances of UTI

These can compress or obstruct the urethra, causing urinary stasis or decreasing urine flow that prevents flushing out of bacteria.

Explain why a catheter can increase chance of UTI

If catheters are not frequently replaces bacteria and fungus can grow.

Explain why a prolapsed bladder can increase chances of UTI

In women, supportive tissues between bladder and vagina weaken and cause the bladder sit at an abnormal angle that leads to urine collecting not completely emptying from the bladder.

Explain supparative cystitis

Inflammation of the bladder characterised by pus on the epithelium.

Explain why increased frequency and urgency of urination are symptoms of cystitis

Inflammation and thickened bladder wall reduces the capacity to hold urine, meaning it fills up quicker, increasing frequency of urination. Additionally, constant inflammation and damage increases nerve signals that increase frequency and urgency.

Define dysuria

Pain when urinating

Explain why lower back pain is a symptom of cystitis

The bladder shares nerve pathways with the lower back, therefore the brain can often misinterpret signals and pain cannot be localised to just the bladder.

Explain pyelonephritis

Infection of the kidneys, mostly by bacteria.

Explain the pathophysiology of acute pyelonephritis

• Obstruction in the urinary tract causes stasis and reflux of urine back into the kidneys

• Urine becomes infected with bacteria which infections the parenchyma

• Infection causes inflammation and oedema which compresses on blood vessels leading to ischaemia and microabscess formation

• Eventually there is necrosis of the parenchyma

Explain polycystic kidney disease

A genetic disorder characterised by the presence of multiple cysts in both kidneys that spread to other organs.

Explain the pathophysiology of autosomal dominant polycystic kidney disease

• Patient born with one mutation in either the PKD1 or PKD2 gene

• Typically in 4th decade of life there is second mutation that causes proliferation and cyst formation

• Fluid is secreted from cysts which causes more and larger cysts to form

Explain the pathophysiology of autosomal recessive polycystic kidney disease

• Patient born with 2 mutated copies of the PKDH1 gene

• Mutated cells proliferate and form cyst formation that is identified within weeks of birth

• For many, inflamed and swollen kidneys compress on the lungs causing respiratory insufficiency

• For half, damage progresses to ESRF

Explain why hypertension is a symptom of polycystic kidney disease

Cysts compress blood vessels that reduce blood flow within the kidneys causing release of renin that activates the RAAS, continuously increasing blood pressure.

Explain why UTIs can be a symptom of polycystic kidney disease

Cysts compress renal tissue and block flow of urine, creating a favourable environment for bacterial growth and replication, leading to infection.

Explain why liver and pancreatic cysts are a symptom of polycystic kidney disease

Mutations are not isolated to cells in the kidney and can affect other organs such as the liver and pancreas with similar structure in terms of tubules and ducts.

Explain why abnormal heart valves, aneurysms and abdominal wall hernias can be symptoms of polycystic kidney disease

Mutation in the PKD1 and 2 genes cause improper formation and dysfunction of polycystic proteins which play a role in the structure of extracellular matrix of connective tissue. Therefore there is a reduction in the strength and integrity of connective tissue that can no longer handle higher pressures, leading to heart valve dysfunction, aneurysms and abdominal wall hernias.

Define glomerulonephritis

Inflammation of the glomeruli

Explain the pathophysiology of proliferative glomerulonephritis

• Bacterial infection leads to immune system mistaking glomeruli for pathogen due to similar structure

• Immune system activation leads to deposition of immune complexes and antibodies that activates the complement system causing:

  • T-cell activation and neutrophil accumulation

    • Release of inflammatory mediators causes inflammation and damage to glomerular filtration membrane

  • Proliferation of mesangial cells

    • Increased number of mesengial cells causes sclerosis and fibrosis in which cells can no longer undergo filtration

• This causes decreased GFR and eventually renal failure

Explain why proteinuria and haematuria are symptoms of glomerulonephritis

Inflammation in the glomeruli causes damage to the glomerular filtration membrane which becomes porous and increases its permeability to allow proteins and red blood cells leak in.

Explain why hypertension is a symptom of glomerulonephritis

• Damage and fibrosis of the glomerulus leads to reduced GFR, stimulating the release of renin and activation of the RAAS.

• Additionally, glomerular damage leads to increased permeability and proteinuria in which proteins are filtered by the glomerulus. This reduces protein concentration in the blood and therefore water drawn into the blood via oncotic pressure. Reduced fluid in the capillaries also activates the RAAS.

Explain why oliguria is a symptom of glomerulonephritis

Damage and fibrosis of the glomerulus leads to decreased GFR and therefore reduced filtering of ions and other substances into filtrate. This decreases water drawn into the filtrate via osmotic pressure, therefore decreasing urine volume.

Differentiate between acute and chronic kidney disease

• Acute - sudden onset and reversible

• Chronic - progressive damage and irreversible leading to ESRF

Explain the pathophysiology of chronic kidney disease

• Systemic disease such as diabetes and hypertension or renal disease cause progressive damage of renal tissue

• This decreases GFR and tubular function leading to ESRF

Explain the 1st stage of chronic kidney disease

Evidence of kidney damage but unaffected GFR of > 90, meaning patient is typically asymptotic, possibly hypertensive

Explain the 2nd stage of chronic kidney disease

Evidence of kidney damage in which GFR is between 60-89 and symptoms include increased creatinine and urea, hypertension, haematuria, proteinuria.

Additionally, decreased GFR leads to build up of serum phosphorus which leads to low calcium. This increases parathyroid hormone secretion to correct calcium levels, increasing oestoclastic activity and leading to bone disease.

Explain the 3rd stage of CKD

• Anaemia due to reduction in erythropoietin production

• Hypovolaemia, sodium loss and dehydration due to damaged tubular function.

• Uraemia due to decreased GFR to between 30-59

Explain the 4th stage of CKD

• GFR continues to decline to between 15-29

• Peripheral oedema due to proteinuria in which decreased protein in the blood means fluid is trapped in tissues

• Metabolic acidosis due to reduced GFR that causes hyperkalaemia. Build-up of potassium ions in the blood causes them to diffuse into cells, swapping with hydrogen ions that increases pH in the blood.

Explain 5th stage CKD

• GFR declines to less than 15

• Oliguria or anuria and severe fluid overload in blood and tissues

• Major electrolyte disturbances

• Systemic disorders such as sexual dysfunction, amenorrhea, cognitive impairments etc.