Renal Pathology Flashcards

1
Q

Function of the Urinary system

A

Filter blood and produce urine
Important in homeostasis of body fluids
Responsible for altering blood composition and pressure forming urine and regulating bodily fluid pH.

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2
Q

Role of the kidney in the urinary system

A

Filters waste and maintains fluid balance

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3
Q

Location of kidneys

A

Upper abdominal cavity on either side of the spine with the right kidney lower than the left.

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4
Q

Ureters role

A

Transport urine to urinary bladder

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5
Q

role of nephrons in the kidney

A

Functional unit
alters blood composition
regulates blood pH
affects blood volume and pressure

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6
Q

Gross structure of the kidney: Renal Cortex and Renal colums - location and structure

A

The outer region of the kidney consists of convoluted tubules, renal corpuscles, blood vessels
Appear granular due to numerous nephrons packed closely together.
Renal Columns: are extensions of the renal cortex that project into the renal medulla separating adjacent renal pyramids and giving stability to the cortex

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7
Q

Gross structure of the kidney: Renal Medulla and Renal Pryamids - location and function

A

-Inner region of the kideny
- Contains renal pyramids
- Renal pyramids consits of renal tubules and collects urine from nephrons. Cone-shaped structures located within the medulla of the kidney
- Medulla appears striated due to arrangement of renal pyramids

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8
Q

Gross structure of the kidney: Renal Pelvis - Location and function

A

Funnel-shaped structure
- Located at the innermost part of the kidney where urine from collecting ducts is collected
- Narrows down to form the ureter which transports urine to the urinary bladder

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9
Q

Gross structure of the kidney: Renal Artery and Vein - function

A
  • Blood vessels that supply and drain the kidney
    renal artery: oxygenated blood to the kidney for filtration
    renal vein: carries deoxygenated blood away for reoxygenation and further transport to the heart
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10
Q

Gross structure of the kidney: Nephrons

A
  • functional units of the kidney responsible for filtering blood and producing urine
  • each nephron consits of a renal corpuscle and renal tubule
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11
Q

Constituents of the renal corpuscle and renal tubule in a nephron

A

renal corpuscle: glomerulus and Bowmans capsule
renal tubules: proximal convoluted tubule, loop of Henle, distal convoluted tubules and collecting duct

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12
Q

Gross structure of the kidney: Renal Capsule - function

A

-Tough fibrous layer surrounding each kidney
- Maintains its shape
- Protects from injury
- Continuous with the ureter

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13
Q

Gross structure of the kidney: Renal Sinus - structure

A

Cavity within the kidney containing: renal pelvis, renal calyces, blood vessels, nerves, lymphatic vessels.

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14
Q

Gross structure of the kidney - Renal hilum

A
  • Indented area
  • Entrance for: renal artery, renal vein, ureter, nerves, lymphatics
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15
Q
A

Collecting and papillary ducts gather urine from nephrons
- urine directed to the renal calyx
- then drained into the pelvis and ureter

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16
Q

Nephrons - Cortical / Juxtamedullary

A

Cortical nephrons: Shorter loops of henle barely penetrating the medulla
Juxtamedullary nephrons: Long loops of henle that extend deep into the medulla, facilitating concentration of urine

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17
Q

Nephron structure and function

A

Distal Convoluted Tubule (DCT)- located distal (farther away) from the glomerulus. The Proximal Convoluted Tubule (PCT) - proximal (closer) to the glomerulus.
Glomerulus (tuft of capillaries): specialized structure within the kidney nephron responsible for initial blood filtration and the formation of primary urine.
Afferent arterioles deliver blood to the glomerulus, efferent arterioles carry blood away
vasa recta: peritubular capillaries surrounding the nephron loops, facilitating exchange and reabsorption in the kidney

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18
Q

SEM of a glomerulus

A
  • Reveals intracate networks of podocytes, enothelial cells, basement membranes necessary for kidney filtration
  • Uses a focus beam of electrons to generate detailed surface images of specimens at a nanometer scale
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19
Q

Glomerulus: Function filtration membrane

A

filtration of water and ions
preents filtration of blood cells and medium-large proteins

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20
Q

Renal Corpuscle: High-resolution images

A

Captures delicate genestrations and interdigitations cruical for maintaining glomeruluar function in health.

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21
Q

Overview of filtration membrane structure in glomerulus

A

Glomeruluar endothelial cells: Large pores (fenestrations) and are leaky. Prevents filtration of blood cells but allows components of blood plasma through.
Basement membrane (basal lamina): lies between endothelium and podocytes. Prevents filtration of larger proteins.
Podocytes: Specialised cells of the bowmans capsule in the kidney. Form pedicles with filtration slits inbetween that prevent filtration of medium-sized proteins.

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22
Q

Lab Investigations to examin kidney tissue samples- Hematoxylin and Eosin (H&E) Staining

A

standard technique used in histology to visualize cellular morphology and tissue architecture.

Hematoxylin stains nuclei blue-purple,

eosin stains cytoplasm and extracellular matrix pink.

method routinely used in the initial examination of kidney tissue to assess general morphology and identify any abnormalities.

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23
Q

Lab Investigations to examin kidney tissue samples- Special Stains (The Renal Set)

A

Collection of special stain used in examination of renal biopsies.

Jones (PAAG): Periodic Acid-Silver Stain - visualizes basement membranes (part of the filtration barrier of the nephron).

MSB: Martius Scarlet Blue or other trichrome stains- assesses fibrosis and scarring.

PAS +/- D: Periodic Acid-Schiff with and without diastase, highlighting carbohydrates like glycogen.

Diastase enzyme breaks down complex carbohydrates like glycogen- helps distinguish between true glycogen and other PAS-positive substances by selectively removing glycogen, aiding in the accurate identification of glycogen-rich structures in tissues.
EVG: Elastic van Gieson stain- visualizes elastic fibers in the tissue.
Congo Red: Detects amyloid deposits that can accumulate in kidney tssues disrupting function and contributing to various disease (AD).

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24
Q

Lab investigations: Immunoflourescence Microscopy (IMF)

A

Immunofluorescence Microscopy (IMF): Detects presence and location of specific protein within a cell.

Uses fluorescent markers such as:

IgG, IgM, IgA, Light Chains (Κ & Λ): Detect immunoglobulins and light chains, which can indicate immune complex-mediated glomerulonephritis.

Light chains in immunoglobulins (antibodies) are components of the antigen-binding region of antibodies and play a crucial role in immune responses - categorized into two types: kappa (κ) and lambda (λ).

CD8, CD4, CD3: Markers for T-cell populations, useful in assessing inflammatory infiltrates.

C3, C1q, C4D: Complement proteins- presence indicates immune complex deposition and complement activation, suggesting conditions like lupus nephritis or antibody-mediated rejection in transplant.

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25
Q

Lab Investigations: Electron Microscopy

A

Provides high-resolution images of kidney tissue at the ultrastructural level- valuable in diagnosing glomerular diseases and other renal pathologies where ultrastructural changes play a significant role.
Provides ultrastructural details.
Uses a beam of electrons to visualize cellular and subcellular structures, such as podocyte foot processes, basement membranes, and mesangial cells.

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26
Q

Renal Biopsy Evaluation: ‘ish’

A

“Ish”: Informal term conveying approximation or uncertainty.

‘always (ish@ used to imply occasionalexceptions variations in EM and IMF use for renal biopsy evaluation depending on the specific case/ insitution.

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27
Q

What is a renal biopsy? What does ut at ‘levels’ mean?

A

Renal biopsies: removal of small piece of tissue to examin under a microscope to diagnose/assess kidney damage.

Cut at “Levels”: Kidney tissue samples cut into thin sections at various levels (superficial, deep , midline) so pathologists can examine different regions of the tissue to asses for variations/abnormalities throughout the sample.

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28
Q

Different types of common renal biopsies

A

Needle Biopsy: Most common type. Needle inserted through skin into the kidney extracting a small tissue sample.

Native Kidney Biopsy: Biopsy performed on native kidneys (patient’s own kidneys.)

Transplant Biopsy: conducted on a transplanted kidney to assess its function or to diagnose any potential issues ( rejection.)

Tumor Biopsy: biopsy may be performed to obtain a tissue sample for diagnosis and to determine the type of tumor present if one is suspected

Wedge Biopsy: small wedge-shaped piece of tissue is removed from the kidney.

Lobe Biopsy: Refers to a biopsy technique where a lobe of the kidney is specifically targeted for sampling.

Resection Biopsy: Removal of a portion of the kidney tissue for examination, often used in cases where a larger sample.

Explant Biopsy: involves removal of entire kidney (explant) for examination, which may be necessary in cases of severe disease or transplantation.

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29
Q

Indications of Renal Biopsy

A
  • Definitive histological gianosis of glomerular/ interstitial disease
  • Severe Proteinuira
  • Haematuria not caused by disease of the lower urinary tract: suggests potential renal or glomerular involvement often necessitating renal biopsy for accurate diagnosis.
  • Acute renal failure (intrinsic renal disease)
  • Glomerulonephritis
  • Other glomerular disorders (e.g amyloid and diabetes)
  • Interstitial Nephritis
  • Renal Transplant ( assessment post-transplant for rejection/complications
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30
Q

Renal biopsy in diagnosing glomerulonephritis

A
  • assesses glomeruluar abnormalities and interstitial diseases by evaluating interstitial inflammation and fibrosis
  • Needle core biopsy followed by examination under microscopes e.g electron, light and immunoflourescence microscopy. Allows for comprehensive evaluation of kidney tissue providing valuable diagnostic information for guiding patient care.
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31
Q

Stages of Renal Biopsy - Fixation

A

Tissue preserved in formalin for light microscopy, glutaraldehyde for electron microscopy (EM), and frozen/Michel’s medium for immunofluorescence microscopy (IMF) to maintain cellular structure and antigen integrity.
-Aldehyde fixatives (e.g formalin and glutaraldehyde), crosslink proteins in tissue samples, preserving cellular structures and preventing degradation for microscopic examination.
-Glutaraldehyde in high concentrations can cause irritation to the respiratory tract, skin, and eyes, and prolonged exposure may lead to sensitization and allergic reactions. Pure morphology, better, slower, lot more toxic

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32
Q

Stages of Renal Biopsy - Processing

A

Samples embedded :
-paraffin for light microscopy
-resin for electron microscopy
-frozen sections for immunofluorescence microscopy
-Prepares samples for respective microscopic examinations while preserving tissue architecture and antigenicity.

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33
Q

Post-Infectious Glomerulonephritis

A

Can be global and diffuse

Enlarged, hypercellular glomeruli

Proliferation of enotherlial and messignal cells

Cresent formation in severe cases- impairs kidney function
Immune system reacts to bacterial antigens deposited in the glomeruli causing inflammation, cellular proliferation and formation of crescents.
this inflammation and damage can progress to chronic kidney disease if left untreated.

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34
Q

Changes seen in Infections/ inflammation in the glomerulus. How does this progress to Chronic Kidney disease?:

A

permeability of the filtration barrier may be altered, potentially allowing bacterial fragments or whole bacteria to pass the through the filtration barrier, triggering an immune response in the kidney contributing to kidney damage
- Activation of inflammatory cells/ release of inflammatory mediators leads to inflammation and renal tissue damage.

35
Q

Special stains

A

Masson trichome: Interstitium stained green

Jones Silver Stain: increased cellularity, highlights glomerular basement membrane for evaluation of basement membrane integrity and thickness.

36
Q

Renal interstitium

A

renal interstitium : the space between the renal tubules and blood vessels within the kidney parenchyma.

-contains various structures including fibroblasts, collagen fibers, and interstitial fluid, and plays a crucial role in maintaining the structural integrity and function of the kidney.

37
Q

Basement membrane

A

specialized extracellular matrix structure

provides structural support

acts as a barrier between epithelial and endothelial tissues.

38
Q

What is diffuse and focal involvement of the glomerulus?

A

Diffuse indicating widespread or generalized involvement of the glomerulus/ generalised thickening of glomerular membrane..? and focal indicating localized or limited involvement of the glomerulus

39
Q

Diffuse Proliferative Glomerulonephritis

A
  • type of glomerulonephritis characterised by widspread diffuse proliferation of glomerular cells. Usually seen in SLE and post in-fectious glomerulnephritis.
40
Q

Double contouring

A

AKA double contour or double basement membrane
-characteristic histological feature observed in evaluation of glomerular diseases
- Refers to the appearance of an additional layer of the glomeruluar basement membrane (GBM)
- seen in certain kidney diseases, particularly those involving immune complex deposition (lupus nephritis)
- presence of double contouring indicated immune complex-mediated injury to the glomeruli: immune complexes accumulate along GBM causing formation of an additional layer or thickening of the basement membrane.

41
Q

Special stains - Silver stains

A

Show spikes between subepithelial deposits in the glomerulus and thickening of Glomerular Basement Membrane

42
Q

What causes spikes between subepithelial deposits in the glomerulus

A
  • typically associated with membranous glomerulonephritis
  • this can be caused by various factors e.g auto immune disesases (E.G SLE), infections (hepatitis B/C), certain medications and malignancies
43
Q

Causes of thickened basement membrane in the kidneys (esp glomeruli)

A

Diabetes mellitus: Chronic high blood sugar levels can lead to thickening of the glomerular basement membrane (GBM) in diabetic nephropathy.

Membranous glomerulonephritis: Immune complex deposition along the GBM can cause thickening in membranous glomerulonephritis.

Aging: Gradual thickening of the GBM can occur as a natural consequence of aging.

44
Q

Consequences of thickened basement membrane in the kidneys

A

mpaired filtration: Thickening of the GBM can reduce the permeability of the glomerular filtration barrier, leading to impaired filtration of blood and proteinuria.

Renal dysfunction: Chronic thickening of the GBM, particularly in conditions like diabetic nephropathy, can contribute to progressive renal dysfunction and decline in kidney function.

Glomerulosclerosis: Prolonged thickening of the GBM can lead to glomerulosclerosis, characterized by scarring and loss of functional glomeruli, ultimately leading to end-stage renal disease (ESRD).

45
Q

Glomerular filtration barrier function

A

-Glomerular filtration barrier in the kidneys selectively filters substances from the blood into the urine while retaining important components in the bloodstream.

46
Q

Substances typicaly filtered in the kidneys

A

Water: The kidneys filter large amounts of water to maintain fluid balance in the body.

Waste products: Metabolic waste products such as urea, creatinine, and uric acid are filtered from the blood and excreted in the urine.

Electrolytes: Essential ions such as sodium, potassium, chloride, and bicarbonate are filtered and regulated by the kidneys to maintain electrolyte balance.

Nutrients: Small molecules such as glucose, amino acids, and vitamins are filtered and reabsorbed by the renal tubules to maintain nutrient balance in the body.

Hormones: Some hormones are filtered and excreted by the kidneys, while others are regulated by renal function.

Toxins and drugs: Various toxins, drugs, and foreign substances are filtered by the kidneys and excreted in the urine to maintain systemic homeostasis.

47
Q

What is Amyloid

A
  • Refers abnormal protein aggregates that accumulate in various tissues and organs disrupting normal function
  • aggregates consist of misfolded proteins that can form insoluble fibrils leading to tissue damage and dysfunction.
  • Amyloid depositis can occur in different organs and is associated with various diesases e.g amyloidosis and AD.
48
Q

Diagnosis of amyloidosis

A
  • Histological examination of affected tissues
  • Immunohistochemistry (visualize specific proteins or antigens in tissue sections using antibodies labeled with a detectable marker, such as an enzyme or fluorescent dye, to aid in the diagnosis and characterization of diseases)
  • sometimes genetic testing - identify specific proteins involved in amyloid deposits.
49
Q

Causes of amyloid deposition in the kidneys

A
  • can be caused by systemic conditions such as amyloidosis, where abnormal proteins (amyloids) accumulate in various organs including the kidneys.
50
Q

Possible consequences of amyloid deposition

A

can lead to renal dysfunction, proteinuria, nephrotic syndrome, and eventually progress to renal failure.

51
Q

Different types of amyloid

A

AA amyloid (associated with chronic inflammatory conditions), AL amyloid (derived from immunoglobulin light chains in plasma cell dyscrasias), and others.

52
Q

Differentiation between types of amyloid

A

typically through histological examination, immunohistochemistry, and molecular analysis- identifies specific proteins involved in amyloid deposition.

53
Q

Elastica van Gieson (EVG) and Congo red special stains

A

EVG: Histological staining technique used to visualize elastic fibers in tissues ( thickening of elastin layer)
Congo read: Amyloid deposition in the kidney

54
Q

Elastin layer and Tunica media in blood vessels

A

Elastic layer: found in the tunica media of blood vessels, providing elasticity and recoil to the vessel walls.
Tunica Media: middle layer composed of smooth muscle cells and elastic fibers, responsible for regulating vessel diameter and blood flow

55
Q

What causes thickening off the elastin layer in arteries?

A
  • Conditions such as hypertension ( high bp) , atherosclerosis ( build-up of plaque in the arteries)
56
Q

Consequences of thickening elastin layer in arteries

A

thickening reduces the flexibility and elasticity of the arterial walls-> decreased arterial compliance -> arteries become stiffer and less able to accommodate changes in blood pressure->can increase the workload on the heart and raise the risk of cardiovascular events such as heart attacks and strokes.

57
Q

Atrophic Tubules

A

-refers to kidney tubules that have undergone a reduction in size or volume due to loss of cells and structural integrity.
- occurs as a result of chronic kidney disease or other renal pathologies, leading to impaired kidney function.

58
Q

Obsolete glomerulus

A

refers to a kidney glomerulus that has become non-functional or inactive due to damage or degeneration.

-occurs as a result of various pathological processes, such as chronic kidney disease, glomerulonephritis, or aging.

  • obsolete glomeruli may be replaced in some cases by scar tissue or fibrosis, leading to a loss of kidney function
59
Q

Electron Microscopy

A
  • Uses heavy metal stains (e.g uranyl acetate and lead citrate) enhance contrast and visualise cellular structures at the nanometer scale
  • stains bind to certain cellular components highlighting them against the background and providing detailed images of subcellular structures
60
Q

Electron Microscopy - Glomerular filter colours

A

ShapeRed- Fenestrated Endothelium

Yellow- GBM

Green -Spiky layer, podocyte layer

61
Q

Kidney Basement Membrane

A
  • helps regulate filtration of waste products and substances from the blood into renal tubules while retaining essential proteins and blood cells
62
Q

Consquences of kidney basement membrane dysfunction

A

lead to various renal diseases, such as nephrotic syndrome and glomerulonephritis.

Thin BM disease, leads to microscopic hematuria (blood in the urine)

Thick BM due to high blood pressure.

63
Q

Special stains Periodic Acid Schiff and IMF IgG

A

PAS: shows Glomerular Basement Membrane (GBM), Glomerular Capillaries, Mesangial Matrix, Tubular Epithelial Cells
IMF (Immunofluorescence) IgG: Uses fluorescent dyes emit fluorescent light, allows for visualization and detection of specific proteins within cells/tissues under fluorescence microscope.
- IgG deposition on basememnt membrane showing thickening
-Coarse granular deposition: indicative of mesangial cell deposits

64
Q

What is Glomerulonephritis? How can it present?

A

Glomerulus – capillary loop with basement membrane which allows passage of specific molecules into the nephron

Glomerulonephritis – inflammation/damage of the glomerular basement membrane resulting in altered function. Relatively uncommon cause of kidney injury

Can present as nephrotic and/or nephritic syndrome

65
Q

What is Nephrotic Syndrome ( non-inflammatory)

A
  • Dysfunction / disruption of glomerular filtration barrier causing increased permeability , more proteins ( esp. albumin) into the urine, edema (swelling), and elevated blood cholesterol levels
66
Q

Causes of Nephrotic Syndrome ( non-inflammatory)

A

Related to alterations in podocytes, endothelial cells and basement membrane of glomerulus rather than direct inflammation

67
Q

Nephrotic Syndrome (non-inflamatory) symptoms

A
  • Not a disease, group of signs and symptoms:
    Massive proteinuria (excreting too much protein in urine) Proteinuria usually > 3.5g / 24hrs (>0.05g / kg / 24hrs in children)
    -Hypoalbuminemia Serum albumin < 30g/l
    -Oedema
  • Hyperlipidemia/ hyperlipiduria
    -Susceptibility to infections
    Unlike nephritic syndrome there is no haematuria
68
Q

Primary causes of disease

A

Diseases/ conditions originating within the organ/system affected

69
Q

Secondary causes of disease

A
  • Causes that arise as a result of another underlying condition or disease process.
  • Neprology: secondary glomeruluar disease occur as a complication of systemic diseases such as diabetes/lupus/infections.
70
Q

Primary glomerular disease examples

A

Minimal change disease (MCD)

Focal segmental glomerulosclerosis (FSGS)

Membranous glomerulonephritis (MGN)

Membranoproliferative glomerulonephritis (MPGN): is the inflammation of the glomeruli along with the deposit of antibodies in their membranes, which makes filtration difficult.

Rapidly progressive glomerulonephritis
- these diseases are characterised by specific patterns of injury to kidney filtering units

71
Q

Secondary Glomerular Disease Examples

A

Diabetic nephropathy

Systemic lupus erythematosus (multiorgan autoimmune disease)

Sarcoidosis Sarcoidosis is a systemic inflammatory disease characterized by the formation of granulomas (small, often microscopic, nodular collections of immune cells) in various organs, particularly the lungs and lymph nodes.

Hepatitis B

Amyloidosis

72
Q

What is a systemic condition?

A
  • medical condition or disease that affects the entire body or multiple organ systems rather than being localized to a specific area or organ.
73
Q

Symptoms of nephrotic syndrome

A

-swelling around the eyes and in the feet and ankles
-foamy urine
- weight gain due to excess fluid retention.

74
Q

Diagnosis of nephrotic syndrome

A
  • Obtain complete medical history
  • Series of tests
  • Blood tests and clinical picture (overall presentation of signs, symptoms, and findings associated with a particular medical condition or disease)
  • Histology needed to confirm
  • diagnosis is based on the underlying cause
75
Q

Nephrotic syndrome:H&E stain and special staining

A

H&E: Exhibits diffuse glomerular changes (alterations or abnormalities that affect the majority or all of the glomeruli) within the kidneys.
special stains like immunofluorescence (IMF) reveals protein accumulation in nephrotic syndrome.

76
Q

Minimal change nephropathy, membranous nephropathy, or diabetic nephropathy characteristics

A

types of nephrotic syndromes characterised by:
-specific patterns of injusry to kidney glomeruli
-leading to poteinuria
- potneital progression to chronic kindey disease

77
Q

Testing for nephortic syndromes

A

Urine test To check the abnormalities in the urine.

Blood test To determine levels of protein albumin.

Kidney biopsy A small sample of kidney tissue for testing.

78
Q

Treatment for nephrotic syndrome - recommended patient diet

A

Foods to eat:

Lean sources of proteins such as Lean meat

Eating a low-salt diet

Low in saturated fat and cholesterol diet

Foods to avoid: Protein rich foods such as eggs and milk- can make nephrotic syndrome worse

79
Q

Neptritic syndrome (inflammatory) symptoms

A

Haematuria (presence of blood in the urine)

Oliguria (reduced urine output)

Azotemia elevated levels of nitrogenous waste products in the blood (Raised  blood urea nitrogen (BUN) and serum creatinine)

Reduced GFR

Fluid overload

80
Q

Nephritic inflammatory mechanism

A

impaired kidney function, leading to decreased filtration capacity and accumulation of fluid in the body, potentially resulting in edema, hypertension, and electrolyte imbalances.
Thin glomerular basement membrane with pores that allow protein and blood into the tubule.

81
Q

Causes of nephritic syndrome (inflammatory)

A
  • Acute post-infectious glomerulnephritis
82
Q

Primary Glomerulonephritis examples

A

-IgA Nephropathy (Berger’s disease) Primary glomerulonephritis characterized by deposition of IgA antibodies in the glomeruli.
-Rapidly progressive glomerulonephritis (Severe form of glomerulonephritis marked by rapid decline in kidney function).
-Proliferative glomerulonephritis Type of glomerulonephritis involving proliferation of cells within the glomeruli.

83
Q

Secondary glomerulonephritis examples

A
  • Henoch-Schonlein purpura - a systemic vasculitis affecting small blood vessels.
  • Vasculitis - Inflammation of blood vessels
  • PSGN
  • Group A haemolytic streptococci of certain serotypes- important infectious causes associated with the development of nephritic syndrome.
84
Q

Diagnosis of nephritic syndrome

A

H&E stain,: nephritic syndrome typically shows glomerular inflammation

Special stains (e.g immunofluorescence (IMF)); differentiate immune complex deposition in nephritic syndrome

Secondary nephritic syndromes may benefit from stains like Congo red to identify amyloid Thin glomerular basement membrane with pores that allow protein and blood into the tubule deposits.