Renal Pathophysiology

FLG 332
Department of Physiology
Dr S Alummoottil
Renal dysfunction
 Renal Failure
• Kidneys fail to carry out the excretory functions.

• Cause:
- renal diseases, systemic diseases or renal defects of
nonrenal origin

• Can occur as acute or chronic disorder.

• Characterised by a decrease in GFR

• GFR is not affected in the initial stage of renal failure.

• More than 75% of renal tissue must be out of action 
impairment of function obvious.
 Renal Failure
Signs and symptoms
 change in urine output
 waste retention and fluid and electrolyte balance
• Early sign:
- inability to concentrate urine
- large volume of urine production  Polyuria
• Next stage:
- inability to produce enough urine to excrete wastes 
Oliguria
• Final Stage:
- inability to produce urine  Anuria
- urea accumulate in the blood  Uraemia
 Renal failure

• Two categories:
1) Acute kidney injury (AKI)
2) Chronic kidney disease (CKD)

• Acute kidney failure  sudden

• Chronic kidney disease  gradual
 Acute kidney injury
• Abrupt loss of kidney function.
• Cause:
- conditions that damage to structures within the kidney.
- decreased blood flow to the kidney.
• Rapid decline in GFR:
 impairs fluid and electrolyte balance
 leads to accumulation of urea and other nitrogenous wastes
in the blood (azotemia)

• Potentially reversible.

• Severe acute kidney injury:

- kidneys may abruptly stop working entirely or almost entirely
 renal replacement therapy such as dialysis
Acute Kidney Injury
 Prerenal AKI
• Abnormality originating outside the kidneys.
• Resulting from decrease in renal blood flow (renal ischemia).
• Cause:
 Volume depletion resulting low BV and low BP due to:
- heart failure with reduced cardiac output
- hypovolemia by dehydration, severe haemorrhage, vomiting,
diarrhea etc
- severe illness e.g. sepsis, arteriosclerosis, thrombosis etc
• Characterise by:
- decrease in RBF
(below 20-25% of normal  renal cells become hypoxic
- decrease in GFR
- Oliguria
- Anuria
- accumulation of water and salts
 Postrenal AKI
• Obstruction of the urinary collecting system.
• Multiple abnormalities in the lower urinary tract.
• Blockage of the Outflow from the kidney, (anywhere from the
calyces to the outflow from bladder) can lead to AKI.
• Chronic obstruction that lasts for several days or weeks can lead
to irreversible kidney damage.
• Causes:
- Obstruction as a result of kidney stones or blood clots.
- Compression of the tract by swollen or neoplastic tissue
- Vesicouretral reflux.
• Kidney stones caused by precipitation of calcium, urate,or cystine
• If urine output of only one kidney is diminished
 no major change in body fluid composition
 because the contralateral kidney can increase urine output.
• Chronic obstruction can lead to irreversible kidney damage
 Intrarenal/ Intrinsic AKI
• Abnormality originating in the kidney.
• Damage to the structures within the kidney.
• Affects blood vessels, glomeruli, or tubules.

• Cause:
- Conditions that injure the glomerular capillaries or
other small renal vessels
- Conditions that damage the renal tubular epithelium
- Conditions that cause damage to the renal interstitium
 Acute glomerulonephritis
• Infection/Inflammation leading to glomerular injury.
• Due to abnormal immune reaction .
• Damaged and inflamed glomeruli cannot filter properly.
• Damage to glomeruli occurs 1-3 weeks after infection elsewhere
in the body.
• Cause:
 Infections (by bacteria: streptococcus (tonsillitis)
staphylococcus, and by viruses: hepatitis B)
 Immune diseases e.g. lupus
- Reaction of antibodies and antigens:
 forms insoluble immune complex (immunoglobulins)
 deposited in the glomerular membrane
- White blood cells become entrapped in the glomeruli.
- Proliferation of cells of the glomeruli (mainly mesangial cells)
- glomeruli get blocked by inflammatory reactions.
 Acute glomerulonephritis
• Proliferation, swelling and leukocyte infiltration block the
glomerular capillary lumen.
• Glomeruli that are not blocked become excessively permeable
allowing the leakage of proteins and red blood cells.
• Symptoms:
-Haematuria (blood in the urine)
- Proteinuria
- Urinating less than usual
- Edema
- Azotemia
- hypertension
• Diagnosis: Urine analysis
 Nephrotic Vs Nephritic Syndrome
• Glomerular disorders.
• Due to inflammation
• Increased permeability of the glomerulus.
• Nephrotic Syndrome:
- Massive proteinuria (loss of proteins particularly albuminuria)
- Hypoalbuminemia
- Hyperlipidemia/hyperlipiduria
- Edema
-Hypercoagulation
• Nephritic Syndrome:
- Hematuria (loss of a lot of blood  red to brown urine)
- Proteinuria (less)
- Oliguria
- Azotemia
- Hypertension
 Pyelonephritis
• Infection of the kidney /upper urinary tract.
• Infection of renal interstitium (intercellular matrix, peritubular
capillaries or tubular damage that destroys individual nephrons
• Cause:
- Different bacteria (especially e.g. Escherichia coli due to fecal
contamination of the urinary tract) ascent to the kidney via
ureters.
- Bacteria can also gain access to the kidney through the
bloodstream or lymphatics.
• Symptoms:
- fever, flank pain, blood or pus in the urine, cloudy urine,
nausea, chills, vomiting and fatigue.
• Diagnosis: physical examination and urine analysis
 Cystitis
• Urinary Tract Infection (UTI).
• Infection of the bladder/ lower urinary tract.
• Cause:
- infection by bacteria e.g. Escherichia coli (fecal
contamination of the urinary tract)
- may occur as a reaction to certain drugs, radiation therapy
or potential irritants, such as feminine hygiene spray,
long-term use of a catheter etc.
• Symptoms:
- persistent urge to urinate, burning sensation when urinating
(dysuria), blood in the urine (haematuria), passing cloudy or
strong-smelling urine, pelvic discomfort, flank pain, fever etc
• Diagnosis: dipstick positive for leukocytes and nitrites.
• Treatment: antimicrobial therapy
 Acute tubular necrosis
• Destruction of epithelial cells in the tubules.
• Result of circulatory shock in many instances.
• Causes:
- Severe ischemia  due to hypotension leading to
lack of oxygen and nutrients result in histologic changes
- Nephrotoxins  toxins or medications that destroy kidney tissues
- Sepsis  reduce renal perfusion
- Occlusion of the tubular lumen by casts and cell debris
 No urine output from the blocked nephrons
• Diagnosis:
- Analysis of serum creatinine
- BUN (blood urea nitrogen)
- Urine analysis: Microscopic analysis, osmolality (Na+
conc), urine volume etc
AKI caused by tubular necrosis
 Physiological effects AKI
Signs and symptoms:
- Edema  due to water and salt overload
- Hypertension  due to water and salt overload
- Acidosis  unable to excrete sufficient hydrogen ions
- Proteinuria and haematuria
- Hypocalcemia  hyperparathyroidism
- Hyperkalaemia  increases in plasma potassium conc:
above 8  (above 8mEq/L)
- Anaemia
- Reduced urine output  retention of metabolic wastes
- Increased thirst
- Rapid pulse
- Nausea, dizziness, vomiting and reduced appetite
 Acute Kidney Injury
• Treatment:
 Focused on prevention and early diagnosis:
- control the diet (high carb, low protein and salt)
- control fluid intake (according to amount of urine production)
- antibiotics to prevent infection
- diuretics to reduce edema
- corticosteroids/immunosuppression
- surgical treatment (e.g. urinary stent or kidney stone removal)
- dialysis
- transplant
 Chronic Kidney Disease (CKD)
• Progressive and long standing impairment.
• Due to permanent loss of nephrons.
• Loss of function of more and more nephrons 
gradually decreases overall kidney function
• Irreversible.
• Decline in function persists for at least 3 months.
• Normal blood electrolyte conc: and blood volumes
until the number of functioning nephrons decreases below
20-25% of normal.
• Life threatening.
• Results from conditions that cause permanent loss of
nephrons.
 Chronic kidney disease (CKD)
• Causes:
- hypertension
- diabetes
- glomerulonephritis
- lupus erythematosus
-polycystic kidney disease
- injury to the renal vasculature:
 Atherosclerosis of the larger renal arteries, with constriction
with progressive sclerotic constriction of the vessels.
 Fibromuscular hyperplasia of one or more of the large
arteries, which also causes occlusion of the vessels.
 Nephrosclerosis, caused by sclerotic lesions of the smaller
arteries, arterioles, and glomeruli.
- renal ischemia and death of kidney tissue.
Vicious cycle of CKD leading to end-stage
renal disease (ESRD)
 Physiological effects of CKD
• Signs and Symptoms
- Uremia and Azotemia
- Acidosis
- Edema
- Anaemia  lack of erythropoietin
- Hypocalcaemia  hyperparathyroidism  due lack of
active vitamin D
- Osteomalcia  due lack of active vitamin D
- Gastrointestinal disorders
- Neurologic complications
- Altered immune function
- Cardiovascular disorders
 Effect of kidney failure on different types
of solutes
• Curve A:
shows the approximate
changes in the plasma conc:
of solutes such as creatinine
and urea that are filtered and
poorly reabsorbed.
• Curve B:
shows the approximate
concentrations for solutes
such as phosphate, urate, and
hydrogen ion.
• Curve C:
shows the approximate concentrations
for solutes such as sodium and chloride.
 Chronic Kidney Disease (CKD)
• Diagnosis:
- Renal biopsy
(for pathological abnormalities e.g. glomerular, vascular or
tubulointerstitial diseases)
- imaging
(ultrasound for kidney damage, CT and MRI scans)
- Urine sediment abnormalities
- Albuminuria
(reflects increased glomerular permeability to macromolecules)
- decreased GFR using serum creatinine
(less than 15ml/min per 1.73m2)
- albumin- creatinine ratio (3.4 mg/mmol or greater)
 Chronic Renal Failure
Treatment:
- control the diet (high carb, low protein and salt)
- control fluid intake (according to amount of urine production)
- Control of blood pressure
- Control of diabetes
- Treatment of original disease
- Hormone therapy
- Kidney dialysis
- Kidney transplant
 Kidney Dialysis
• Works on diffusion across an artificial semi- permeable membrane.
• Patients blood is circulated through a container.
• Blood is separated from the dialysing fluid by a semi-permeable
membrane.
• Membrane allows the excess inorganic substances , water and
metabolites to pass into the dialysing fluid.
• Blood cells and plasma proteins remains in the blood.
• Kidney dialysis is done several hours every few days.
• Prolong the life span of patients.
 Artificial kidney

• https://www.youtube.com/watch?v=hc5e5cY
dshI
 Case Study
• A 58-old obese woman with hypertension, type 2 diabetes,
and chronic renal insufficiency is admitted to hospital after a
right femoral neck fracture sustained in a fall. Recently she
has been complaining of fatigue. Her medications include
angiotensin-converting enzyme inhibitor, a beta blocker, a
diuretic, calcium supplementation and insulin. On
examination, her blood pressure is 148/60 mm Hg. She is
oriented and able to answer questions appropriately.
1) Discuss the pathogenesis of bone disease in chronic kidney
disease. How could this explain the patient’s increased
likelihood of a fracture after a fall.
2) Give reasons for her fatigue.
3) State two main possible causes of chronic kidney disease in
this patient.