Renal Disorders

PATH1016

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Learning Objectives
• Examine the etiology contributing to the
development of different types of renal failure
conditions
1. Pre-Renal
2. Intrarenal
3. Post-Renal
• Differentiate between acute and chronic renal
conditions according to their underlying
pathophysiological mechanisms
• Examine the manifestations and management of
acute and chronic renal conditions

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 REVIEW
Review of Kidneys

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 Roles of kidneys

• Filtration of the blood

• Removes wastes
• Maintains appropriate
concentrations of
REVIEW OF electrolytes
KIDNEYS • Maintains acid base
balance
• Regulation of blood volume
and blood pressure
• Activation of vitamin D
• Production of erythropoietin

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 REVIEW

Review of Kidneys
• Functional unit of the kidneys is
the nephron
• Each nephron contains a
glomerulus, tubule and collecting
duct
1. Glomerulus
• Tuft of capillaries and
filtration surfaces for filtering
blood
2. Tubule
• Reabsorption and secretion
of various ions and molecules
• Proximal tubule, loop of
Henle, distal convoluted
tubule
3. Collecting Duct
• More reabsorption/secretion
and delivery of urine to
bladder 5
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Increase of
Disequilibrium
When metabolic of fluids and
wastes in the electrolytes
Decreased
activation
Decreased
erythropoietin

Kidneys circulation of vitamin

D
Fail? pH imbalance
Results in Leads to
decreased anemia
calcium
absorption and
subsequent
hypocalcaemia
General Types of Kidney Failure
• The cause is decrease in blood supply to
Pre-renal the kidneys
failure • Ischemia to the kidney
• Problem is outside the kidneys

Intrinsic failure The cause is a problem within the kidneys

(intrarenal)

Post renal This is a problem with the collecting

system outside of the kidneys
failure (ureters/bladder/urethra)

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Acute
Kidney
Injury

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 1. GFR - Glomerular filtration rate
• Estimates how much blood passes through the
glomeruli each minute.
• As GFR goes down we see a DECREASE in the
functional filtration rate of the kidney.
Lab Tests 2. BUN (blood)
of Kidney • Measures urea level in blood which indicates
retention of nitrogenous products
Function
3. Creatinine (blood)
• Creatinine is a by-product of muscle
metabolism and the more that is retained
(goes up) in the blood means GFR is
decreasing

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 PRERENAL FAILURE
Disruption of blood flow to kidneys

Loss of blood flow damages the filtration ability of the

kidney = loss of function

Decreased filtration function Example: increase of sodium

(GFR) leads to electrolyte retention
imbalances

Prolonged disruption of blood flow will lead to permanent

ischemic damage (tubular epithelial cells).
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PRE-RENAL FAILURE: Causes
Disruption of blood flow to kidneys will lead to ischemic
damage (ischemia) = impaired perfusion.
Impaired perfusion can be caused by:
1. Dehydration
2. Shock
• Cardiogenic shock
• Septic shock
• Hemorrhagic (blood loss)
3. Heart failure
4. Burns
5. Drugs - nephrotoxins
• Ones that dilate blood peripheral blood vessels

Pre Renal Injury video

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 POST RENAL FAILURE
• Caused by obstruction of urine outflow from the
ureter, bladder, or urethra.

• Urine backs up into the kidneys from bladder and

causes damage to the functional units of the kidney.

Causes
• Ureter – calculi and strictures
• Bladder – tumors or neurogenic bladder
• Urethra – prostatic hyperplasia (enlarged prostrate)
• This is the most common cause

• Treatment consists of treating underlying cause

before permanent functional damage sets in
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 INTRINSIC RENAL FAILURE
• Includes diseases of the glomeruli and tubes
• May be acute or chronic conditions that cause
sclerosis of the functional units of the kidneys
• May affect one or both kidneys

Causes of glomerular injury

• Immunologic (primary and secondary
glomerular disease)
• Non-immunologic (diabetes, hypertension,
drugs, chemicals)
• Heredity mechanisms (Alport syndrome)
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Acute Renal Failure

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 Causes of
acute
renal
failure

VanMeter & Hubert (2017),

Gould’s Pathophysiology

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Acute Abrupt is onset, usually reversible.

renal
Rapid decline in kidney function marked
failure by:
(ARF)
Inability to maintain fluid balance
Usually reversible
when underlying
pathology is
treated before
permanent
Inability to maintain electrolyte balance
damage to
functional unit
sets in Inability to excrete nitrogenous wastes.
Prerenal and Post
Renal etiologies. Azotemia
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Acute renal failure (ARF)
Azotemia – gold standard manifestation of renal
failure

Accumulation of nitrogenous wastes in the blood

1. Urea
2. Nitrogen What does a decrease
3. Uric acid in GFR mean in renal
pathology?
4. Creatinine

Decrease in GFR
(glomerular filtration rate).
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Diagnosis & Treatment of acute
renal failure
Prevention and early diagnosis is key
• Identifying patients at risk
• Recording of urine output
• Urine tests (proteinuria)
• Blood tests (BUN, creatinine)
• Identifying and correcting cause
• Monitoring and treating infections
• Hemodialysis or continuous replacement therapy
(CCRT)
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 The most vulnerable part of the functional
unit of the kidney is the tubular structures

ATN describes an acute destruction of the

Acute tubular epithelial cells with acute
impairment of renal function.
tubular
necrosis Etiological factors
(ATN)
• Ischemia Ischemia is a condition in which blood flow (and thus oxygen) is restricted
or reduced in a part of the body.
• Sepsis
• Nephrotoxic effects of drugs
• Tubular obstruction
• Toxins from massive infection

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Acute tubular necrosis (ATN)

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Clinical course of ATN
• time of onset of the precipitating event until tubular
Onset or injury occurs.
initiating
phase

• marked decrease in GFR; with sudden retention of metabolites such

as potassium, creatinine, urine output low
Maintenance • Fluid retention results in edema; pulmonary congestion
phase

• repair of renal tissue occurs

Recovery • urine output increases and serum creatinine falls.
phase

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Comparison of ARF and CKD

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CHRONIC KIDNEY DISEASE

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Chronic Kidney Disease (CKD)

Progressive decline in kidney function due to

permanent loss of nephrons.

Can result from multiple Hypertension

etiologies most common are Diabetes
those that are intrinsic in Glomerulonephritis
nature Autoimmune

CKD can also present after serial acute episodes of

kidney failure or an acute episode where permanent
damage results

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 Chronic Kidney Disease
• Fewer nephrons are functioning.

• Decreased GFR greater than 3

months.

• Remaining nephrons must filter

more:
• Hypertrophy

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Chronic Kidney Disease
End-stage
renal failure:Uremia is a dangerous
condition that occurs
• Uremia when waste products
associated with
decreased kidney
• More thanfunction
blood.
build up in your

90%
nephrons
lost oliguria is low urine
output, while anuria
• Marked means no urine output
oliguria or
anuria

VanMeter & Hubert (2017),

Gould’s Pathophysiology

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Stages of Chronic Kidney Disease

Porth, 2012
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Clinical manifestations of CKD
Disorders of fluid, Disorders of calcium
electrolyte and acid- and phosphorous
base balance (serum balance and bone
pH) disease

Disorders of
Disorders of
cardiovascular
hematologic function
function

Disorders associated
Disorders of drug
with accumulation of
elimination
nitrogenous wastes

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 Clinical Manifestations of CKD
Chronic Renal Failure (CRF) results in
disorders of the following:

1. Fluid, electrolyte and acid-base

balance
2. Calcium and phosphorous balance See pg. 897 Figure 34-4
and bone disease in textbook (Norris,
3. Hematologic function 2020) for summary

4. Cardiovascular function
5. Accumulation of nitrogenous wastes
6. Drug elimination

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Chronic Kidney Disease

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1. Fluid, Electrolytes & Serum pH
Manifestation Pathological Rationale

Hyponatremia • Loss of ability to reabsorb Sodium in tubules

(low serum sodium) Inability to concentrate urine (polyuria)

Hyperkalemia • 90% of potassium is excreted through kidneys

(High serum potassium) • Inability to remove potassium with severe
kidney impairment
• Diet high in K+ can then lead to high levels of
serum potassium
Metabolic Acidosis • Loss of ability to eliminate hydrogen ions
(Low serum pH) (acidic)
• Loss of ability to reabsorb bicarbonate (buffer
of acid)
• This manifestation directly results in a
demineralization of bone
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2. Calcium, Phosphate & Bone
Manifestation Pathological Rationale
Hyperphosphatemia • Inability to eliminate phosphate results in rising serum
(high serum phosphate.
phosphate) • Phosphate and Calcium are linked inversely
Hypocalcemia • With high phosphate levels, calcium is excreted at higher
(low serum calcium) amounts leading to low serum levels.
• Calcium absorption is also impaired by a deficiency in
Vitamin D
• Hypocalcemia triggers a parathyroid response
Vitamin D deficiency • Kidneys activate the Vitamin D that is absorbed through
the GI tract.
• Inability to activate Vitamin D occurs with progressing
kidney impairment
• Low Vit D leads to decreased absorption of Calcium in GI
Bone Reabsorption • Low Calcium results in stimulation of Parathyroid gland
(Decay of bone) leading to reabsorption (decay) of bone
• Decay of bone replaces serum Calcium and acts as a
bufferPATH1016
of acidosis
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 Manifestations of disorders of
Calcium, Phosphate & Bone
• Bone pain and muscle weakness
• Develop gait abnormalities
• Spontaneous fractures
• Impaired healing of fractures
• Metastatic calcifications
• Blood vessels
• Soft tissues
• Lungs
• Heart
• Hyperparathyroidism
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Calcium, phosphate, PTH

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 Calcium, phosphate, PTH

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Copyright © 2019 Elsevier Canada, a division of Reed Elsevier Canada, Ltd.
Treatment of Disorders of
Calcium & Phosphate

Dietary
Restrictions of Phosphate binding
foods high in antacids: Ca
phosphorus carbonate
content (milk)

Activated vitamin Hyperparathyroidi

D supplement sm medications

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 3. Disorders of
hematologic function
Anemia
• Kidneys primary site for production of
erythropoietin which controls red
blood cell (RBC) production.

• Renal failure erythropoietin

production is insufficient to stimulate
RBCs

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Manifestations 1. Weakness
2. Fatigue
of hematologic 3. Depression
dysfunction: 4. Insomnia
5. Decreased cognitive functioning.
Anemia 6. Increased Heart Rate
• Due to decreased blood
viscosity
7. Can worsen patients with angina
8. Spontaneous bleeding

Treatment
• Iron Supplement, orally or
intravenously.

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 4. Disorders of cardiovascular
function
Cardiovascular disease is worsened or
develops due to CKD
Some common but not exclusive are
• Hypertension
• Left ventricular hypertrophy
• CHF
• Pericarditis (inflammation of pericardium)

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 5. Disorders associated with
accumulation of nitrogenous wastes
Azotemia is an elevation of blood urea nitrogen (BUN) and serum creatinine levels

• Azotemia is an early sign of kidney failure.

• BUN rises
• Uremic state occurs
• accumulation of organic waste products in the blood
• Uremic state characterized by alterations in
1. Neuromuscular function
2. GI
3. Immune function
4. GU & sexual function
5. Skin
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 Manifestations of Uremic State
System Disorder Specific Manifestation Caused by Accumulation of Uremic
toxins
Neuromuscular • Peripheral Neuropathies (sensory & motor)
• Demyelination
• Encephalopathy (inflammation of the brain)
Gastrointestinal • Anorexia
• Nausea and vomiting
Immune system • Decreased white blood cells
• Impaired cell-mediated immunity
Genitourinary & • Impotence in males
Sexual • Decreased libido in mailes
• Infertility in females (Ammenorrhea)
• Decreased vaginal secretions
Integumentary • Dry Skin
(Skin Integrity) • Pruritis
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6. Disorders of drug elimination
• CKD and its treatment can interfere with
pharmacokinetics of drugs
1. Absorption
2. Distribution
3. Elimination of drugs.
• Progressive failure of kidney function drugs
leads to accumulation of active drug and/or
metabolites
RENALLY ADJUSTED DOSE of MEDICATIONS

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Medical Slow the progression of the
disease (loss of kidney
Management function):
Goals
1. Prompt treatment of
UTIs
2. Blood pressure control
3. Glycemic control in
diabetics
4. Smoking Cessation
5. Dietary management

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 Goal to provide optimal
nutrition with tolerable levels
of metabolic wastes.
Dietary 1. Restriction of dietary
management proteins.
in CKD 2. Adequate calories in the
form of carbohydrates and
fats.
3. Restriction of Sodium
intake
4. Restriction of Potassium
5. Restriction of phosphorus
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Management of CKD
How does
• Hemodialysis Hemodialysis is a treatment to filter wastes and water
from your blood,
dialysis
work?

• Peritoneal dialysis Peritoneal dialysis is a treatment for kidney failure that uses the lining of your
abdomen, or belly, to filter your blood inside your body.
Organ transplantation is a medical procedure
in which an organ is removed from one body
and placed in the body of a recipient,

• Transplantation

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 Peritoneal Dialysis

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http://www.tynesidekpa.org.uk/peritoneal-dialysis/
Hemodialysis System

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 Failing Kidneys and Treatment
DocMikeEvans Options
https://youtu.be/mi34xCfmLhw
Video link

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