Special pathology - renal pathology Flashcards
Name the main parts of a nephron in order: (6)
- Glomerulus
- Proximal convoluted tubulue
- Descending loop of Henle
- Ascending loop of Henle
- Distal tubule
- Collecting duct
Function of the 2. Proximal convoluted tubule (3)
reabsorbs ions, water and nutrients;
actively transports toxins and drugs from the interstitial fluid into the filtrate.
adjusts filtrate pH
Function of the 3. Descending loop of Henle
aquaporins, water reabsorption
Function of the 4. Ascending loop of Henle
Na+ and Cl- reabsorption
Function of the 5. Distal tubule
selective secretion
ion reabsorption for pH and electrolyte balance
Function of the 6. Collecting duct
reaborbs more solutes and water
What are macula densa?
in the wall of the distal tubule, are salt sensors that detect filtrate Na+ concentration in tubule, and then generate paracrine chemical signals in the juxtaglomerular apparatus to control renin release from the juxtaglomerular epithelial cells
(thus renal blood flow and glomerular filtration is controlled by macula densa)
an increase in sodium chloride concentration in the distal tubule detected by macula densa cells would result in
reduced paracrine stimulation of juxtaglomerular cells and thus vasoconstriction of afferent arterioles.
This demonstrates the macula densa feedback, where compensatory mechanisms act in order to return GFR to normal.
Constriction of the afferent arterioles has two effects: it increases the vascular resistance which reduces renal blood flow, and it decreases the pressure downstream from the constriction, which reduces the GFR.
A decrease in sodium chloride concentration in the distal tubule detected by macula densa cells initiates a signal that has two effects:
(1) it decreases resistance to blood flow in the afferent arterioles, which raises glomerular hydrostatic pressure and helps return the glomerular filtration rate (GFR) toward normal, and
(2) it increases renin release from the juxtaglomerular cells of the afferent and efferent arterioles, which are the major storage sites for renin.
renin increases blood pressure
The renin-angiotensin-aldosterone system is a
series of reactions designed to help regulate blood pressure.
When blood pressure falls, the kidneys release the enzyme
renin into the bloodstream.
What happens next?
Renin splits angiotensinogen, a large protein that
circulates in the bloodstream, into pieces.
angiotensin I is produced.
Angiotensin I, which is relatively inactive, is split by
angiotensin-converting enzyme (ACE) into angiotensin II, a hormone, which is very active.
Angiotensin II causes? (3)
the muscular walls of arterioles to constrict, increasing blood pressure.
Also triggers the release of aldosterone from the adrenals and the release of vasopressin/ADH from the pituitary.
Aldosterone and vasopressin cause the kidneys to do what
retain sodium.
(Aldosterone also causes the kidneys to excrete potassium.)
The increased sodium causes water to be retained, thus increasing blood volume and blood pressure.
Aldosterone causes the kidneys to retain sodium.
How does it affect potassium?
Aldosterone also causes the kidneys to excrete potassium.
Renal diseases can be divided in two ways. What are they?
Into either;
1. Glomerular diseases
2. Tubular diseases
Or into;
1. ACUTE KIDNEY INJURY
2. CHRONIC KIDNEY DISEASE
Polyuria
production of abnormally large volumes of dilute urine.
urine output greater than 2 ml/kg/hour
Oliguria
the production of abnormally small amounts of urine.
urine output less than 1-2 ml/kg/hour in a well-hydrated patient.
no urine output
anuria
the production of abnormally small amounts of urine is known as
oliguria
Azotemia
High concentrations of nitrogen-containing compounds in
the blood.
Either N as Blood urea nitrogen
(BUN – nitrogen product from liver) or
creatinine (metabolic product of nitrogen from muscles).
azotemia can be further described as one of 3 options
Pre-renal
Renal
Post-renal
examples of Pre-renal causes of azotemia (5)
Dehydration
Heart diseases (hypotension – low filtration rate)
Shock
A diet rich in protein (only elevated BUN)
Bleeding in the digestive tract (only elevated BUN)
examples of renal causes of azotemia (1)
renal failure
examples of post-renal causes of azotemia (2)
Urinary tract obstruction
Bursting of the bladder
What is uremia?
azotemia + clinical signs
(loss of appetite, vomiting, diarrhea, bleeding in the
stomach and intestines, mouth
What is the difference between uremia and azotemia?
Pretty much means, azotemia with clinical signs.
So azotemia only describes increased concentration of nitrogenous compounds in blood but its without clinical signs.
Describe Assessment of GFR in clinical practice
(glomerular filtration rate)
Estimation of GFR is done using circulating biomarkers.
creatinine is the most important one but many things influence this marker so interpretation can be tricky
What types of Physiological factors affect creatinine concentration (5)
- Age
- Breed
- Exercise
- Feeding
- Body size effect
(Small dogs have higher GFR, lower creatinine)
Disadvantages of using creatinine as a biomarker for GFR (5)
- There is a delay of 48-72 h for increase from an actual injury
- It does not differentiate between pre-renal causes and acute kidney injury (AKI) so you need to rule out pre-renal problems (heart, hydration etc.)
- It does not differentiate between acute and chronic process
- Non-linear relationship with GFR
- Influenced by muscle mass, breed, size, age
relationship between serum creatinine and GFR
Non-linear relationship between decrease in glomerular filtration rate (GFR) and increase in serum creatinine.
What is cystatin C?
A biomarker of GFR.
- Constantly produced in all nucleated cells –cleared by glomerular filtration.
- Clinically used in humans (eGFR equation) – analysis is simple.
- Sensitivity and specificity depends on chosen cut-off value.
- Canine studies and reviews report as promising marker of
GFR.
What is SDMA?
SDMA (symmetric dimethylarginine) is a biomarker specifically for kidney function.
- Originates from intracellular protein metabolism, cleared
by kidneys.
SDMA is less impacted by extrarenal factors, including
body condition, advanced age, and disease state. Correlates well to (GFR).
Why is Anaemia is a common complication of advanced CKD? (3)
- Uremia damages red blood cells
- Uremia may lead to gastrointestinal ulcers, causing bleeding.
- Reduced erythropoietin secretion from the damaged kidney leads to an inability to replace red blood cells as they reach the end of their life span.
The anaemia is usually non-regenerative and slowly progressive.
Urine Specific Gravity Measures
urine concentration with a Refractometer
Hyposthenuria has an SG of
SG < 1.008 (dilute)
Hypersthenuria means
concentrated urine
Isosthenuria has an SG of
1.008-1.012 (it is neither dilute nor concentrated)
What type of “-thenuria” is worst?
Isosthenuria
SG 1.008-1.012
Isosthenuria may be seen in disease states as chronic kidney disease and acute kidney injury in which the kidneys lack the ability to concentrate or dilute the urine and so the initial filtrate of the blood remains unchanged despite the need to conserve or excrete water based on the body’s hydration status. has the same osmolality as that of plasma.
The kidneys can concentrate urine if urine specific gravity is:
Dog
Cat
Horse, cattle
Dog > 1.030
Cat > 1.035
Horse, cattle > 1.020
urinary casts are
Cylindrical structures formed in the distal convoluted tubules and collecting ducts of the nephron.
- where tubular flow rates are slowest
– One end is smooth and rounded
– One end is irregular and jagged
made up of Protein + cells
can be seen upon urine sediment microscopy
Proteinuria is a general term that describes
the presence of any type of protein in the urine
– Albumin
– Globulins
– Bence Jones proteins.
What are bence-jones proteins?
A small protein made by plasma cells.
What is the predominate protein in urine in dogs and cats
in both health and renal disease.
albumin
Proteinuria of renal origin results from: (2)
- loss of selective glomerular filtration resulting in an
increased amount of plasma protein in the filtrate - impaired resorption of the filtered protein
Leading cause of chronic kidney disease
glomerular diseases
Common in dogs, less common in cats.
More common in middle-aged to older dogs.
glomerular diseases can be divided into (2)
1) Familial glomerulopathies
2) Secondary to systemic disease processes such as:
infectious
inflammatory disorders
Neoplastic
Long term effects of high blood pressure
Immune mediated
Occur with other kidney diseases
Dogs with advanced kidney disease will develop (4)
- Hypoproteinemia due to hypoalbuminemia
- azotemia
- hyperphosphatemia
- metabolic acidosis
the most common glomerular disease in cats is
Membranous nephropathy is the most common glomerular disease in cats; other forms appear to be less common.
Glomerulosclerosis is
scarring of the glomerulus. This causes a loss of protein into the urine.
What is a membranous glomerulopathy?
is one of many glomerular diseases characterized by massive proteinuria
immune-complex mediated disease wherein immune complexes are deposited on the abluminal (subepithelial) side of the glomerular basement membrane (GBM).
Immune complex deposits are composed of immunoglobulin (usually IgG) and antigen.
Acute tubular injury (ATI) represents
the initial phase of development of structural and functional kidney damage
reasons for Initiation of ATI (4)
Initiation of Acute tubular injury
- occurs from naturally occurring disease (e.g., toxic insult, renal ischemia, infectious disease)
- can occur secondary to other critical illnesses
- secondary to the systemic inflammatory response
- or from therapeutic intervention with nephrotoxic agents
Common biomarkers for acute tubular injury (2)
Urine glucose
Urine protein
Fanconi Syndrome is
a syndrome of inadequate reabsorption in the proximal renal tubules
Fanconi Syndrome proximal tubular defect results in: (5)
- glucosuria
- aminoaciduria
- proteinuria
- phosphaturia
- Hypophosphatemia
Fanconi syndrome is inherited in what percentage of what breed
10% to 30% of all Basenjis.
clinical signs - by 4 to 8 years of age
Treatment is supportive.
Cystinuria is
is an Inherited proximal tubular defects characterized by high concentrations of the amino acid cystine in the urine, leading to the formation of cystine stones in the kidneys, ureters, and bladder.
It is a type of aminoaciduria. “Cystine”, not “cysteine,” is implicated in this disease; the former is a dimer of the latter.
Breed predisposition: newfoundlands
Hyperuricosuria means
presence of excessive amounts of uric acid in the urine.
can form concrements
most commonly found in the Dalmatian!
Bulldog and Black Russian terrier, Spanish Waterdog
acute kidney injury is an
abrupt (within hours) decrease in kidney function
Phases/pathophysiology of acute kidney injury (4)
- initiation
- extension
- maintenance
- recovery/ repair
intrinsic renal AKI damage can be localized to what tissues more specifically?
tubular damage
glomerular damage
interstitial damage
vascular damage
biomarkers for AKI (4)
urea
creatinine
phosphorus
metabolic acidosis
chronic kidney disease is defined as
Structural and/or functional abnormalities of one or both kidneys that have been continuously present for 3 months or longer.
CKD is not a single disease, there are many different causes of it.
by the time the animal shows signs of kidney disease
the cause may no longer be apparent
causes of CKD: (5)
- congenital malformation of the kidneys (birth defects)
- chronic bacterial infection of the kidneys with or without kidney stones (pyelonephritis)
- high blood pressure (hypertension)
- diseases associated with the immune system (e.g.
glomerulonephritis) - acute kidney disease can lead to CKD
pathological changes in renal structure in CKD can be (5)
interstitial inflammation
interstitial fibrosis
tubular atrophy
glomerulosclerosis
nephron loss
pathpphysiological changes in renal function in CKD (3)
decrements of GFR
maladaptations
uremic syndrome
Clinical signs of CKD (8)
■ Polyuria and polydipsia
■ Anorexia
■ Vomiting
■ Weight loss and loss of body condition
■ Pallor (because of anemia)
■ Oral ulceration (because of uremia)
■ Halitosis (because of uremia)
■ Acute blindness (due to hypertension)
Urine protein/creatinine ratio is
a widely used initial method to estimate daily protein excretion in urine.
the diagnosis and management of proteinuric renal diseases and the staging of chronic kidney disease depend on accurate identification and quantitation of proteinuria.
UPCR is calculated by dividing the level of protein (mg/dl) in a spot urine test by the creatinine level (mg/dl).
pyelonephritis is
inflammation involving the renal pelvis and renal
parenchyma, “kidney infection”.
In companion animals (usually):
complicated urinary tract infection due to bacteria that have ascended from the lower urinary tract.
untreated bacterial pyelonephritis can cause
permanent and progressive damage of the involved kidney aka CKD
also can lead to septicemia
Note:
clinical signs and diagnostic findings are sometimes
mild, especially if pyelonephritis is only unilateral.
What is renal secondary hyperparathyroidism
Renal hyperparathyroidism (rHPT) is a common complication of chronic kidney disease characterized by elevated parathyroid hormone levels secondary to derangements in the homeostasis of calcium, phosphate, and vitamin D.
Patients with rHPT experience increased rates of cardiovascular problems and bone disease.
