Skin + Kidney + Cardiac + RT Flashcards
Where do benign epithelial neoplasms develop from?
They develop from stem cells residing in the epidermis and hair follicles.
Do benign epithelial neoplasms undergo malignant transformation?
Generally, they do not undergo malignant transformation.
How does seborrheic keratosis present?
It presents as raised, round, discolored plaques on the extremities or face.
What cells are involved in seborrheic keratosis?
It involves proliferating basal epidermal cells.
What microscopic feature is characteristic of seborrheic keratosis?
Keratin pseudocysts on the epidermis, sometimes hyperkeratosis.
Who is most commonly affected by seborrheic keratosis?
It is most common in the elderly.
What is a rare but possible association with seborrheic keratosis?
In rare cases, it can appear as a paraneoplastic syndrome associated with GI tract carcinoma.
What genetic mutation is involved in the pathogenesis of seborrheic keratosis?
Activating mutations in the Fibroblast Growth Factor receptor.
What causes actinic keratosis?
It is usually a result of chronic exposure to sunlight.
What is the risk associated with actinic keratosis?
It has the potential to become malignant (Squamous Cell Carcinoma - SCC).
What genetic mutation is commonly associated with actinic keratosis?
TP53 mutation.
How does actinic keratosis appear morphologically?
It is usually less than 1 cm in diameter, brown or red, and rough.
What cytological features are seen in actinic keratosis?
Cytological atypia in the lower part of the epidermis and parakeratosis of the stratum corneum.
Where do sebaceous adenomas typically appear?
In the head and neck region of older individuals.
What do sebaceous adenomas look like?
They present as flesh-colored papules less than 5 mm.
What syndrome is associated with sebaceous adenomas?
Muir-Torre syndrome.
What internal malignancy is often associated with sebaceous adenomas?
Mainly colon carcinoma.
What is the morphology of sebaceous adenomas? Histo
Lobular proliferation of sebocytes maintaining an organoid appearance with expansion of germinative basaloid cell layers at the periphery.
What is squamous cell carcinoma?
Malignant proliferation of squamous cells.
How does squamous cell carcinoma typically present?
As a red scaling nodular mass, usually on sun-exposed sites, commonly the face and lower lip.
What are the risk factors for squamous cell carcinoma?
Sunlight exposure, albinism, xeroderma pigmentosum, immunosuppressive therapy, toxin exposure (arsenic), and chronic inflammation.
What genetic mutations are involved in squamous cell carcinoma?
Mutations in TP53, HRAS, and loss of function in Notch receptors.
How does squamous cell carcinoma affect the immune system?
It has an immunosuppressive effect on the skin by impairing antigen presentation by Langerhans cells.
What are the morphological features of squamous cell carcinoma?
Atypical cells at all levels of the epidermis, invasive tumors penetrating the basement membrane, variable degrees of differentiation.
What is the treatment for squamous cell carcinoma?
Excision; rarely metastasizes, but the likelihood of metastasis relates to lesion thickness and invasion depth.
What is basal cell carcinoma?
Malignant proliferation of the basal cells of the epidermis.
How does basal cell carcinoma typically present?
As an elevated nodule with a central ulcerated crater surrounded by telangiectasia (‘pink, pearl-like papule’), usually on the upper lip.
What genetic pathway is often mutated in basal cell carcinoma?
Mutations in the Hedgehog pathway and p53.
What are the morphological features of basal cell carcinoma?
Tumor cells resemble basal epidermal cells, with horizontal growth along the epithelio-dermal junction and vertical growth into the dermis, potential local invasion of bone or facial sinuses.
What is the recommended treatment for basal cell carcinoma?
Radical removal to prevent extensive local invasion.
What is actinic keratosis a precursor lesion for?
Squamous cell carcinoma.
How does actinic keratosis present?
As a hyperkeratotic, scaly plaque, often on the face, back, or neck.
What is keratoacanthoma?
A well-differentiated squamous cell carcinoma that develops rapidly and regresses spontaneously.
T66 Where are melanocytes located and what is their function?
Melanocytes are present in the basal layer of the epidermis and are responsible for skin pigmentation.
From where are melanocytes derived?
They are derived from the neural crest.
What precursor molecule is used by melanocytes to synthesize melanin?
Tyrosine is used as the precursor molecule to synthesize melanin in melanosomes.
To which cells do melanocytes pass melanosomes?
They pass melanosomes to keratinocytes.
What is a melanocytic nevus?
It is a benign tumor of melanocytes, also known as a nevus (congenital).
What is malignant melanoma?
It is a malignant tumor of melanocytes.
How do melanocytic nevi typically appear?
They appear as brown, uniformly pigmented, small (<5mm) solid regions of elevated skin (papules) with well-defined, rounded borders.
What are junctional nevi?
They are initial nevi composed of oval cells that grow in nests along the dermoepidermal junction.
What are compound nevi?
They are junctional nevi that have grown into the underlying dermis as nests or cords of cells.
What are intradermal nevi?
In older lesions, the epidermal nests may be lost completely, leaving pure intradermal nevi.
What mutations are commonly found in benign nevi?
Activating mutations in BRAF, or less commonly in RAS.
What is the function of the BRAF gene?
The BRAF gene encodes a Ser/Thr kinase involved in directing cell growth.
What morphological changes occur in superficial nevus cells?
Superficial nevus cells are larger, less mature, tend to produce melanin, and grow in nests.
How do deeper nevus cells differ from superficial nevus cells?
Deeper nevus cells are smaller, more mature, produce little to no pigment, and grow in cords or as single cells; the deepest cells grow in fascicles.
What is a dysplastic nevus?
Dysplastic nevi consist mainly of compound nevi marked by cytological atypia with irregular nuclei and hyperchromasia.
What genetic mutations are associated with dysplastic nevi?
Mutations in BRAF or RAS.
How can dysplastic nevi occur?
They may occur sporadically or in a familial form (autosomal dominant inheritance).
What is the significance of familial dysplastic nevi?
They are considered markers for an increased risk of developing melanoma.
How do dysplastic nevi appear morphologically?
They are larger than most acquired nevi (>5mm), vary from flat macules to slightly raised plaques, show variable pigmentation, and have irregular borders.
Where do dysplastic nevi typically occur?
They can occur on both sun-exposed and non-exposed surfaces.
What pattern do nevus cells exhibit in dysplastic nevi?
Nevus cells exhibit a lentiginous pattern, replacing normal basal cells at the dermoepidermal junction.
What dermal changes are seen in dysplastic nevi?
Lymphocytic infiltration into the superficial dermis, melanin phagocytosis by dermal macrophages, and linear fibrosis surrounding epidermal nests of melanocytes.
What is melanoma?
Malignant neoplasm of melanocytes and the most common cause of death from skin cancer.
What is the primary cause of melanoma?
Sunlight exposure.
What hereditary condition is associated with melanoma?
Dysplastic nevus syndrome, an autosomal dominant disorder characterized by the formation of dysplastic nevi that may progress to melanoma
What genetic mutation is found in 40% of familial melanomas?
Mutations in the p16 gene, which encodes a cyclin-dependent kinase inhibitor regulating the G1-S transition.
What mutations are common in sporadic melanomas?
Somatic activating mutations in the proto-oncogenes BRAF and NRAS.
What is the growth pattern of melanoma?
Initially, melanoma grows radially (horizontally within the epidermis and superficial dermis) without metastasis or angiogenesis. Later, it grows vertically into the deeper dermal layers, with greater metastatic potential.
What are the morphological features of melanoma?
Melanomas show large variation in pigmentation (black, brown, red), irregular and notched borders, and malignant cells growing in poorly-formed nests or as individual cells at all epidermal levels.
How do melanoma cells differ from nevus cells?
Melanoma cells are larger, with large nuclei, chromatin clumped at the periphery, and prominent eosinophilic nucleoli (“cherry red”).
What are the clinical features of melanoma?
Melanomas mostly arise in the skin but can also involve oral and anogenital mucosal surfaces, esophagus, meninges, and the eye.
What are the ABCs of melanoma?
Asymmetry, Border, Color, Diameter, Evolution (change of an existing nevus).
How is the probability of melanoma metastasis predicted?
By measuring the depth of invasion (Breslow thickness) from the top of the granular cell layer of the epidermis.
T67 What are soft tissues and from where are they derived?
Soft tissues are non-epithelial tissues except bone, cartilage, CNS, hematopoietic, and lymphoid tissues. They are derived from the mesoderm and are often called mesenchymal tissues.
How are sarcomas different from carcinomas?
In sarcomas, both parenchyma and stroma are derived from the same origin and cannot be separated, whereas in carcinomas, parenchyma and stroma can be easily separated.
Which type of nerve tumors belong to soft tissue tumors despite their derivation?
Tumors of the peripheral nerves, which are derived from the neuroectoderm.
From what do soft tissue tumors originate?
They originate from tissue-specific Mesenchymal stem cells (MSCs).
Where can Mesenchymal stem cells (MSCs) be found in the body?
MSCs can be found in the placenta, umbilical cord blood, adipose tissue, adult muscle, corneal stroma, and the dental pulp of deciduous baby teeth.
What percentage of invasive malignancies do soft tissue tumors represent?
They represent less than 1% of all invasive malignancies but cause 2% of all cancer deaths.
Where do 40% of soft tissue tumors occur?
40% of soft tissue tumors occur in the lower extremities.
What is the common treatment for soft tissue sarcomas?
Wide surgical excision (frequently limb-sparing), with irradiation and systemic therapy reserved for large high-grade tumors.
What diagnostic methods are important for classifying soft tissue tumors?
Histology, immunohistochemistry, electron microscopy, cytogenetics, and molecular genetics.
What are the characteristic histological patterns of soft tissue tumors?
Spindle cell, epithelioid, pleomorphic, small blue cell, biphasic
How is the grading of soft tissue tumors determined?
Grading is based on differentiation, mitotic activity, and the extent of necrosis.
What is the TNM system used for in soft tissue tumor staging?
The TNM system considers the size and depth of invasion (T), nodal involvement (N), and metastasis (M)
What is the correlation between tumor size and metastasis in soft tissue tumors?
Tumors larger than 20 cm have an 80% chance of metastasis, whereas tumors 5 cm or smaller have a 30% chance.
How are soft tissue tumors graded on a scale from I to III?
Grading is based on differentiation (1-3), mitotic count (1-3), and necrosis (1-3). Higher scores indicate higher grades.
What is a lipoma?
A benign tumor of fat, most common in adults.
What are the characteristics of most lipomas?
They are solitary lesions, mobile, slowly enlarging, and painless masses.
What can multiple lipomas suggest?
Multiple lipomas may suggest the presence of rare hereditary syndromes.
What are conventional lipomas?
Soft, yellow, well-encapsulated masses of mature adipocytes, without pleomorphism.
What is a spindle cell lipoma?
A slow-growing subcutaneous tumor mainly found in the back, neck, and shoulders of older men.
What is a myolipoma?
A benign tumor consisting of fat cells with a variable number of muscle cells.
What is a myelolipoma?
A benign tumor composed of mature adipocytes and hematopoietic cells
What is a pleomorphic lipoma?
Characterized by giant cells resembling small flowers with overlapping nuclei.
What is an angiolipoma?
A subcutaneous nodule with vascular structures, commonly painful.
What is a liposarcoma?
A malignant neoplasm of adipocytes, usually occurring in individuals aged 50-60 years.
Where do most liposarcomas arise?
In deep soft tissues or the retroperitoneum.
What are well-differentiated liposarcomas?
Malignant lesions associated with amplification of a region in the long arm of chromosome 12.
What are dedifferentiated liposarcomas?
They consist of a well-differentiated liposarcoma adjacent to a more poorly differentiated tumor.
What are myxoid (round cell) liposarcomas?
Associated with translocation between chromosomes 12 and 16, affecting transcription factors in adipocyte differentiation.
What is the morphology of myxoid liposarcomas?
Characterized by an abundant mucoid extracellular matrix and the presence of lipoblasts indicating fatty differentiation.
What is nodular fasciitis?
A rapidly growing, self-limited fibroblastic proliferation, often resulting from trauma.
What is the morphology of nodular fasciitis?
Tightly woven uniform spindle cells and collagen in a storiform arrangement, with a few lymphocytes and vascular channels.
What is myositis ossificans?
Characterized by the presence of metaplastic bone and ossification of muscle, developing in the proximal muscles of athletic adolescents and young adults after trauma.
What are fibromatoses?
Benign soft tissue tumors that are locally aggressive but do not metastasize. They often recur after surgical removal.
What are superficial fibromatoses?
They arise in the superficial fascia and can be associated with trisomy 3 and 8.
What are deep fibromatoses?
They include desmoid tumors that arise in the abdominal wall, mesentery, and muscles of the trunk and extremities, and can be part of Gardner syndrome.
What is a fibrosarcoma?
A malignant neoplasm composed of fibroblasts, typically found in the deep tissues of the thigh, knee, and retroperitoneal area.
What is the recurrence and metastasis pattern of fibrosarcoma?
They recur locally after excision in 50% of cases and can metastasize, usually to the lungs.
What is the morphology of fibrosarcoma?
Soft, unencapsulated, infiltrative masses with areas of hemorrhage and necrosis, showing all degrees of differentiation on histologic examination.
T68 What are skeletal muscle neoplasms usually classified as?
They are almost all malignant.
What is a rhabdomyoma and where is it most often found?
A rare benign hamartomatous tumor of striated muscle, most often found in the heart.
How can rhabdomyomas be classified?
They can be classified as adult type, fetal type, and genital type
What is the most frequent primary tumor of the heart in infants and children?
Rhabdomyoma
What is rhabdomyosarcoma?
A malignant neoplasm of skeletal muscle usually appearing in children and adolescents.
Where do rhabdomyosarcomas most commonly occur?
In the head and neck region or the urogenital tract.
What chromosomal translocation is often found in rhabdomyosarcoma?
The translocation t(2;13).
What are the morphological types of rhabdomyosarcoma?
Embryonal, alveolar, and pleomorphic variants.
What is a sarcoma botryoides?
A subtype of rhabdomyosarcoma that appears as soft, gelatinous, grape-like masses, typically arising next to the bladder or vagina.
What is a rhabdomyoblast?
A cell that appears in all types of rhabdomyosarcoma, exhibiting granular, eosinophilic cytoplasm rich in thick and thin filaments.
What are the immunohistochemical markers for rhabdomyosarcoma?
Desmin and actin.
How is rhabdomyosarcoma typically treated in children?
With chemotherapy, which is often effective.
What is a leiomyoma?
A benign smooth muscle tumor, common and well-defined, most commonly arising in the uterus.
What chromosomal rearrangements are associated with leiomyomas?
Chromosomal rearrangements of chromosomes 6 and 12.
What is the morphology of leiomyomas?
They are very well-defined, gray-white masses with a whorled cut surface and can be intramural, submucosal, or subserosal.
What happens to large leiomyomas after menopause?
They may become collagenous and even calcified.
What is a leiomyosarcoma?
A malignant smooth muscle tumor that usually occurs in adults, more commonly in females, often as solitary tumors.
Where do leiomyosarcomas typically metastasize?
To the lungs.
How do leiomyosarcomas of the uterus usually arise?
De novo from mesenchymal cells of the myometrium, not from pre-existing leiomyomas.
What is the morphology of leiomyosarcomas?
They are soft, hemorrhagic, and necrotic with spindle cells, cigar-shaped nuclei, cytological atypia, and mitotic activity.
What differentiation is often seen in peripheral nerve tumors?
Evidence of Schwann cell differentiation.
What familial tumor syndromes are associated with peripheral nerve tumors?
Neurofibromatosis type 1 (NF1) and type 2 (NF2).
What is a schwannoma?
A benign, encapsulated tumor composed of Schwann cells, often causing local compression of the involved nerve or adjacent structures.
What genetic mutation is associated with NF2?
A dominant loss-of-function mutation of the merlin gene on chromosome 22.
What are the two histological patterns seen in schwannomas?
Antoni A (dense areas with spindle cells and nuclear palisading forming Verocay bodies) and Antoni B (loose meshwork of cells and stroma).
What is a neurofibroma?
A benign peripheral nerve sheath tumor.
What are the three types of neurofibromas?
Localized cutaneous, plexiform, and diffuse neurofibromas.
What distinguishes a plexiform neurofibroma?
It grows diffusely within a nerve or nerve plexus, often associated with NF1, and may evolve into a malignant tumor.
How do neurofibromas differ from schwannomas in morphology?
Neurofibromas are not encapsulated and may appear circumscribed or diffuse, with neoplastic Schwann cells mixed with other cell types.
What is an MPNST?
A highly malignant sarcoma that is locally invasive and often shows evidence of Schwann cell derivation.
What percentage of MPNSTs arise from NF1?
50% of MPNSTs arise from NF1.
What is the morphology of MPNST?
Large, poorly defined tumor masses, highly cellular with anaplasia, necrosis, infiltrative growth pattern, pleomorphism, and high proliferative activity.
What causes NF1?
An autosomal dominant disorder caused by a mutation in the tumor suppressor neurofibromin on chromosome 17.
What are the clinical features of NF1?
Learning disabilities, seizures, skeletal abnormalities, vascular abnormalities with arterial stenoses, pigmented nodules of the iris (Lisch nodules), and pigmented skin lesions.
What is the typical age range for synovial sarcoma patients?
20-40 years old.
Where do synovial sarcomas usually develop?
In deep soft tissues around large joints of the extremities, mainly the knee joint.
What chromosomal translocation is associated with synovial sarcoma?
t(X;18).
What are the two types of synovial sarcoma based on morphology?
Monophasic (one cell type – spindle cell) and biphasic (both spindle and epithelial-like cells).
Where do synovial sarcomas commonly metastasize?
To the lungs, bones, and regional lymph nodes.
T69 What is the functional unit of the kidney?
The nephron, composed of the glomerulus and a tubular system.
What is the glomerular capillary wall composed of?
Three layers: fenestrated endothelium, glomerular basement membrane, and visceral epithelium
What are the three sub-layers of the glomerular basement membrane?
Lamina rara interna, lamina rara externa, and lamina densa
What cells compose the visceral epithelium of the glomerular capillary wall?
Podocytes with interdigitating processes creating filtration slits.
What is the role of mesangial cells in the glomerulus?
They support the glomerular structure, have contractile and proliferative abilities, lay down connective tissue, and secrete active mediators.
What factors determine the selective permeability of the glomerular filtration barrier?
The size and charge of the molecule, with cationic molecules being more permeable.
What is azotemia?
An elevation of blood urea nitrogen and creatinine levels, reflecting a decreased glomerular filtration rate (GFR).
What is prerenal azotemia?
Azotemia due to hypo perfusion of the kidney, resulting in decreased GFR
What is postrenal azotemia?
Azotemia due to urine flow obstruction below the level of the kidney.
What is uremia?
A condition where azotemia gives rise to clinical manifestations, with metabolic and endocrine alterations incident to renal damage.
What are the major syndromes of renal disease?
Nephritic syndrome, nephrotic syndrome, asymptomatic hematuria, rapidly progressive glomerulonephritis, acute kidney injury, chronic kidney disease, urinary tract infection, and nephrolithiasis (renal stones).
What characterizes nephritic syndrome?
Glomerular injury leading to hematuria, oliguria, azotemia, and hypertension.
What characterizes nephrotic syndrome?
Heavy proteinuria (>3.5g/day), hypoalbuminemia, severe edema, hyperlipidemia, and lipiduria.
What characterizes asymptomatic hematuria?
Non-nephrotic proteinuria, usually due to mild glomerular abnormalities.
What characterizes rapidly progressive glomerulonephritis?
Nephritic syndrome that progresses to renal failure in weeks to months.
What characterizes acute kidney injury?
Acute oliguria or anuria and azotemia, which may result from glomerular, interstitial, vascular, or tubular injury.
What characterizes chronic kidney disease?
Prolonged symptoms and signs of uremia due to progressive scarring in the kidney.
What characterizes urinary tract infection?
Bacteriuria and pyuria, which may be symptomatic or asymptomatic, affecting the kidney (pyelonephritis) or bladder (cystitis).
What characterizes nephrolithiasis?
Renal colic, hematuria without casts, and recurrent stone formation.
What are primary glomerular diseases?
Diseases where the kidney is the predominant organ involved.
What are secondary glomerular diseases?
Diseases caused by a systemic condition, such as SLE, hypertension, diabetes mellitus, or Alport syndrome.
What are the two types of immune reactions causing glomerular diseases?
Antibody-associated and cell-mediated.
What causes injury by circulating immune complexes?
Deposition of soluble circulating antigen-antibody complexes in the glomerulus, leading to activation of the complement system and recruitment of leukocytes.
What causes in situ immune complex injury?
Antibodies reacting with glomerular antigens or molecules planted within the glomerulus, inducing a granular pattern under immunofluorescence microscopy.
What is anti-glomerular basement membrane (GBM) glomerulonephritis?
A condition where autoantibodies are produced against the GBM, resulting in severe glomerular damage and possibly Goodpasture syndrome if the antibodies cross-react with alveoli.
What is the role of T cells in glomerular injury?
Sensitized T cells may cause glomerular injury, although their exact role in glomerulonephritis is not well established.
What mediators are involved in immune injury of the glomerulus?
Complement-leukocyte mediated injury, monocytes and macrophages, platelets, resident glomerular cells, and thrombin.
What is podocyte injury?
Morphologic changes such as effacement of foot processes, vacuolization, retraction, and detachment of podocytes from the GBM, leading to proteinuria.
What happens in nephron loss?
Maladaptive changes in remaining nephrons, such as hypertrophy and increased single nephron GFR, leading to further endothelial lesions, podocyte injury, and glomerular sclerosis.
T71 What characterizes nephrotic syndrome?
Proteinuria leads to hypoalbuminemia and edema, due to increased permeability of glomerular disorders.
What is massive proteinuria?
Daily protein loss in the urine of 3.5g or more.
What is hypoalbuminemia?
A serum albumin concentration of less than 3g/100 ml.
What is generalized edema?
Also called anasarca, results from decreased plasma oncotic pressure, often starting with periorbital edema.
What causes hyperlipidemia and lipiduria in nephrotic syndrome?
Increased hepatic lipoprotein synthesis, possibly triggered by hypoalbuminemia or massive proteinuria.
What causes the hypercoagulable state in nephrotic syndrome?
Loss of antithrombin III.
What is the primary cause of nephrotic syndrome in children
Primary illness, often idiopathic.
What is the primary cause of nephrotic syndrome in adults?
Usually a secondary manifestation of a systemic disease.
What are common secondary causes of nephrotic syndrome?
Diabetes and systemic amyloidosis.
What is minimal-change disease?
A common cause of nephrotic syndrome in children, characterized by damage to the podocyte layer, usually idiopathic or associated with Hodgkin lymphoma.
What is the pathogenesis of minimal-change disease?
Damage to podocyte foot processes caused by T-cell derived cytokines, leading to proteinuria.
What is the morphology of minimal-change disease?
Glomeruli appear normal in light microscopy, but podocyte foot processes disappear in electron microscopy. No immune complex deposits; negative immunofluorescence.
What are the clinical features of minimal-change disease?
Nephrotic syndrome without hypertension, preserved renal function, selective proteinuria (albumin), and good response to corticosteroids.
What is membranous nephropathy?
A progressive disease common in ages 30-60, characterized by subepithelial immune complex deposits along the GBM and diffuse thickening of the capillary wall.
What are the causes of membranous nephropathy?
Most cases are idiopathic. Secondary causes include infections (hepatitis B/C, syphilis), malignant tumors (melanoma, lung and colon carcinoma), SLE, autoimmune conditions, and certain drugs.
What is the pathogenesis of membranous nephropathy?
Chronic immune complex glomerulonephritis induced by antibodies reacting with intrinsic or planted glomerular antigens, often targeting the phospholipase A2 receptor.
What is the morphology of membranous nephropathy?
Diffuse subepithelial immune deposits cause GBM thickening, granular appearance in immunofluorescence, spike and dome pattern in electron microscopy, and podocyte foot process effacement.
What are the clinical features of membranous nephropathy?
Development of nephrotic syndrome, sometimes with lesser degrees of proteinuria. Poor response to steroids, with 40% progressing to renal failure within 2-20 years.
What characterizes FSGS?
Sclerosis affecting some, but not all glomeruli (focal involvement) and involving only segments of each affected glomerulus (segmental involvement).
What are the primary and secondary causes of FSGS?
Primary causes are usually idiopathic. Secondary causes include HIV, heroin use, sickle cell disease, nephron loss, and mutations affecting podocyte proteins.
What is the pathogenesis of primary FSGS?
The initiating event is thought to be podocyte injury, possibly progressing from minimal-change disease, with deposition of hyaline masses and entrapment of plasma proteins and lipids.
What is the morphology of FSGS?
Affected glomeruli exhibit segmental increased mesangial matrix, obliterated capillary lumens, hyalinosis, lipid droplets, and podocyte foot process effacement. Progression leads to global sclerosis with tubular atrophy and interstitial fibrosis.
What are the clinical features of FSGS?
Higher incidence of hematuria and hypertension, non-selective proteinuria, poor response to corticosteroids, and development of end-stage renal failure in 50% of cases.
What characterizes MPGN?
Alterations in the GBM and mesangium, with proliferation of glomerular cells. Patients may exhibit nephrotic or nephritic symptoms, or sub-nephrotic proteinuria.
What are the types of MPGN and their associations?
Type I (80%): Subendothelial deposits associated with HBV and HCV. Type II (Dense Deposit Disease): Intramembranous deposits associated with C3 nephritic factor, leading to overactivation of complement.
What is the morphology of MPGN?
Large glomeruli with lobular appearance, proliferation of mesangial and endothelial cells, thickened GBM with a “tram track” appearance due to splitting from mesangial and inflammatory cell processes.
What are the clinical features of MPGN?
Poor response to steroids, often progresses to chronic renal failure. In lupus patients, membranous GN is the cause of nephrotic syndrome, but most common lupus kidney disease is membranoproliferative glomerulonephritis with nephritic syndrome.
T70 What characterizes nephritic syndrome?
Glomerular inflammation, resulting in hematuria, oliguria, azotemia, and hypertension.
What is hematuria and how does it occur in nephritic syndrome?
Hematuria is the presence of blood in the urine, caused by inflammatory injury to capillary walls.
What are oliguria and azotemia?
Oliguria is low urine output, and azotemia is high levels of nitrogen-containing compounds, both resulting from reduced GFR.
What causes hypertension in nephritic syndrome?
Fluid retention and release of renin from ischemic kidneys.
What are the histological features of nephritic syndrome?
Proliferation of glomerular cells and infiltration of inflammatory leukocytes.
What commonly causes acute postinfectious glomerulonephritis?
Develops following a streptococcal infection, typically beta-hemolytic group A strains.
What is the typical patient demographic for poststreptococcal glomerulonephritis?
Usually seen in children, but can also occur in adults.
What is the pathogenesis of poststreptococcal glomerulonephritis?
Immune complexes from streptococcal infections deposit in glomeruli, activating the complement system and causing leukocyte infiltration and glomerular cell damage.
What are the hallmark lesions of PSGN? Acute Postinfectious Glomerulonephritis
Subepithelial “humps” seen in electron microscopy
What are the clinical features of poststreptococcal glomerulonephritis?
Fever, nausea, nephritic syndrome with mild oliguria, azotemia, hypertension, and gross hematuria (cola-colored urine).
What characterizes IgA nephropathy?
Deposition of IgA in the mesangium, causing recurrent microscopic or gross hematuria.
Who is most commonly affected by IgA nephropathy?
Children and young adults.
What triggers IgA nephropathy in genetically susceptible individuals?
Mucosal infections leading to increased and abnormal IgA production.
What are the morphological features of IgA nephropathy?
LM: Varying degrees of glomerulonephritis. IF: Mesangial deposition of IgA and often C3. EM: Electron-dense deposits in the mesangium.
What is the clinical course of IgA nephropathy?
Gross hematuria after respiratory infections, recurrent episodes, and risk of chronic renal failure in 25-50% of cases over 20 years.
What causes hereditary nephritis?
Mutations in genes encoding GBM proteins, most commonly seen in Alport syndrome.
What is Alport syndrome?
A hereditary condition causing nephritis, sensory hearing loss, and eye disorders due to mutations in type IV collagen α chains.
What are the morphological features of Alport syndrome?
Early: Normal glomeruli. Late: Secondary sclerosis, foamy interstitial cells, GBM thinning, splitting, and lamination (basketweave appearance).
What is the typical clinical course of Alport syndrome?
X-linked inheritance, affecting males more severely. Hematuria and proteinuria from age 5-20, with renal failure developing between 20-50 years.
T72 What characterizes rapidly progressive glomerulonephritis (RPGN)?
Progressive loss of renal function with severe oliguria, azotemia, and laboratory findings of nephritic syndrome. Histologically, crescents form between Bowman’s capsule and the glomerular capillary network.
What are crescents in RPGN?
Crescents are formations seen between Bowman’s capsule and the glomerular capillary network due to the proliferation of parietal epithelial cells.
What characterizes anti-GBM crescentic glomerulonephritis in immunofluorescence?
Linear deposits of IgG and C3 on the GBM.
What is Goodpasture syndrome?
A condition where antibodies deposit on both the GBM and alveolar capillaries, leading to hematuria and hemoptysis, commonly seen in young adult males.
What is the morphology of kidneys in anti-GBM crescentic glomerulonephritis?
Kidneys are enlarged and pale with petechial hemorrhages on the cortical surface, and glomeruli show segmental necrosis and crescents.
What is the characteristic finding in immunofluorescence for immune-complex mediated crescentic glomerulonephritis?
Granular pattern of staining.
What conditions are commonly associated with immune-complex mediated crescentic glomerulonephritis?
Poststreptococcal GN, diffuse proliferative GN (e.g., SLE-kidney), IgA nephropathy, and Henoch-Schonlein purpura.
What is the morphology of immune-complex mediated crescentic glomerulonephritis?
Segmental necrosis and crescents, with underlying immune complex GN in segments of glomeruli without necrosis.
What defines pauci-immune crescentic glomerulonephritis?
No anti-GBM antibodies or immune complex deposition detected in immunofluorescence or electron microscopy, but segmental necrosis and crescents are seen.
What systemic vasculitis conditions may include crescentic GN as a component?
Microscopic polyangiitis (pANCA) and Wegener granulomatosis (cANCA).
What antibodies are typically found in pauci-immune crescentic glomerulonephritis?
Antineutrophil cytoplasmic antibodies (ANCA).
What distinguishes Churg-Strauss syndrome from other vasculitides?
Presence of eosinophilia, asthma, and granulomatous inflammation.
T74 What drugs are commonly associated with acute drug-induced interstitial nephritis?
Synthetic penicillins (methicillin, ampicillin), synthetic antibiotics (rifampin), diuretics (thiazides), non-steroidal anti-inflammatory agents (analgesics).
What is the pathogenesis of drug-induced interstitial nephritis?
The drug acts as a hapten, binds to tubular cell components, and induces an immune reaction. Elevated IgE suggests type I hypersensitivity, and mononuclear or granulomatous infiltrate suggests T-cell mediated type IV hypersensitivity.
What are the morphological features of drug-induced interstitial nephritis?
Profound interstitial edema and infiltration by eosinophils, lymphocytes, and macrophages. Glomeruli are usually normal, except with NSAID-induced cases where podocyte foot processes disappear.
What are the clinical features of drug-induced interstitial nephritis?
Begins 2-40 days after drug exposure, with fever, eosinophilia, rash, hematuria, minimal proteinuria, leukocyturia, and possibly increased serum creatinine and oliguria.
What is acute tubular injury (ATI) and its most common cause?
ATI is characterized by the destruction of tubular epithelial cells, leading to acute renal failure. The most common cause is ischemic injury.
What are the causes of acute tubular injury?
Ischemic injury, toxic substances (ethylene glycol, mercury, lead, carbon tetrachloride, methyl alcohol), and nephrotoxic drugs.
What is the pathogenesis of toxic acute tubular necrosis?
Ingestion or inhalation of toxic substances interferes with epithelial cell metabolism, leading to proximal tubular epithelium necrosis and acute renal failure.
What is the pathogenesis of ischemic acute tubular necrosis?
Inadequate renal blood flow from hypotension or shock leads to vasoconstriction, reduced GFR, oliguria, and ischemic injury to tubular cells and basement membrane.
What are the morphological features of ischemic ATI?
Cell swelling, focal tubular epithelial necrosis and apoptosis, thinning or loss of proximal tubule brush border, vacuolization of cells, and sloughing of tubular cells into the urine.
What are the morphological features of toxic acute tubular necrosis?
Proximal tubular epithelium necrosis with preserved basement membrane, no nuclei, and intense eosinophilic homogeneous cytoplasm. Interstitium and glomeruli are not affected.
What causes diffuse cortical necrosis (DCN)?
Diminished renal arterial perfusion due to vascular spasm, microvascular injury, or DIC, resulting from conditions like pregnancy, HIV, shock, trauma, SLE, sickle cell anemia, congenital heart disease, anemia, or placental hemorrhage.
What are the five forms of DCN?
Focal: Focal necrosis of glomeruli without thrombosis, patchy necrosis of tubules.
Minor: Larger areas of necrosis with vascular and glomerular thrombosis.
Patchy: Necrosis occupying 2/3 of the cortex.
Gross: Almost entire cortex involved, widespread arterial thrombosis.
Confluent: Widespread glomerular and tubular necrosis without arterial involvement.
What is the morphology of DCN?
Grossly: Kidney appears red (congested) with yellowish-white spots (infarcts). Microscopically: Ischemic necrosis, massive leukocyte infiltration in deeper areas, and intravascular and intraglomerular thrombosis.
T75 What are simple cysts in the kidneys?
Generally non-harmful lesions that are 1-5 cm in diameter, usually confined to the cortex, with smooth contours, avascular, and produce fluid under ultrasonography.
What is the significance of dialysis-associated acquired renal cysts?
They occur in patients with end-stage kidney disease undergoing prolonged dialysis and increase the risk of developing renal cell carcinoma.
What characterizes ADPKD? Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Multiple expanding cysts on both kidneys that eventually destroy the parenchyma, caused by mutations in PKD1 or PKD2 genes.
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
What are the clinical features of ADPKD?
Symptoms usually appear around age 40 and include flank pain, hematuria, hypertension, and urinary infections. Liver cysts and aneurysms in the circle of Willis may also occur.
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
What is the role of polycystin-1 and polycystin-2 in ADPKD?
Polycystin-1 (encoded by PKD1) is involved in cell-cell and cell-matrix interactions. Polycystin-2 (encoded by PKD2) functions as a Ca2+ membrane channel. Mutations in either gene result in the disease.
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
What characterizes ARPKD?
Multiple closed cysts not in continuity with the collecting system, caused by mutations in the PKHD1 gene.
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
What are the clinical features of ARPKD?
Most common forms are perinatal and neonatal. Newborns present with manifestations at birth and may die quickly from hepatic or renal failure. Survivors develop liver cirrhosis (congenital hepatic fibrosis).
Autosomal Recessive Polycystic Kidney Disease (ARPKD)
What is the role of fibrocystin in ARPKD?
Fibrocystin, encoded by the PKHD1 gene, is a receptor-like protein that may be involved in tubulogenesis and the maintenance of duct-lumen architecture.
What are the two types of medullary cystic disease?
Medullary sponge kidney: Cystic dilatation of collecting tubules, often associated with nephrolithiasis.
Nephronophthisis medullary cystic disease complex: Autosomal recessive disorders causing chronic renal disease, characterized by corticomedullary cysts, atrophy, and interstitial fibrosis.
What are the clinical features of nephronophthisis medullary cystic disease complex?
Initial manifestations are polyuria and polydipsia. Diagnosis is difficult due to lack of serologic markers and small cysts. Variants include infantile, juvenile, adolescent, and adult types, often with retinal abnormalities.
What is hydronephrosis?
Dilation of the renal pelvis and calyces, with accompanying atrophy of the parenchyma, caused by obstruction to urine outflow.
What are common causes of hydronephrosis?
Congenital: Atresia of the urethra, valve formations, renal artery compression, renal ptosis.
Acquired: Stones, tumors, benign prostatic hyperplasia, inflammation, neurogenic bladder, pregnancy.
What is the pathogenesis of hydronephrosis?
Obstruction leads to increased tubular pressure, filtrate backflow into interstitium, compression of renal vasculature, arterial insufficiency, venous stasis, and interstitial inflammation, eventually causing fibrosis.
What is nephrolithiasis?
Formation of stones in the urinary collecting system, most often in the kidneys, more common in men. Risk factors include high solute concentration and low urine volume.
What are the clinical features of nephrolithiasis?
Colicky pain with hematuria and unilateral flank tenderness. Small stones may pass into the ureter, causing intense pain radiating to the groin (renal colic).
Nephrolithiasis (Kidney Stones)
What are the types and causes of kidney stones?
Calcium oxalate/phosphate: Most common, often due to idiopathic hypercalciuria.
Ammonium magnesium phosphate (struvite): Caused by urease-positive bacterial infections.
Uric acid: Associated with hot climates, acidic urine, gout, and diseases with increased cellular turnover.
Cysteine: Genetic defects in amino acid transport, seen in children.
How are different types of kidney stones treated?
Calcium oxalate/phosphate: Hydrochlorothiazide.
Ammonium magnesium phosphate: Surgical removal and pathogen eradication.
Uric acid: Hydration, urine alkalization, and allopurinol (for gout).
Cysteine: Hydration and urine alkalization.
T76 Urolithiasis, hydronephrosis, obstructive uropathy
T78 Diseases involving renal vessels, diabetic nephropathy
T77 What are small cortical papillary adenomas?
Benign tumors less than 0.5 cm in diameter, common and have no clinical significance.
What is the most common malignant tumor of the kidney?
Renal cell carcinoma, derived from renal tubular epithelium, primarily located in the cortex.
What are the common metastasis sites for renal cell carcinoma?
Lungs and bones.
What are the risk factors for renal cell carcinoma?
Smoking, obesity, hypertension, exposure to cadmium, and polycystic disease from chronic dialysis
What are the clinical features of renal cell carcinoma?
Painless hematuria, palpable abdominal mass if large enough, dull flank pain, fever, weight loss, and paraneoplastic syndromes.
What are the three most common forms of renal cell carcinoma?
Clear cell carcinoma, papillary renal cell carcinoma, and chromophobe renal carcinoma.
What is clear cell carcinoma?
The most common type of renal cell carcinoma, derived from the proximal convoluted tubule, located predominantly in the cortex.
What are the gross and microscopic features of clear cell carcinoma?
Gross: Solitary large yellow mass with areas of cystic softening or hemorrhage. Microscopically: Tumor cells with clear cytoplasm, small round nuclei, and vacuolated lipid-laden cytoplasm.
What genetic mutation is associated with clear cell carcinoma?
Loss of VHL (chromosome 3) tumor suppressor gene, leading to increased IGF-1 and HIF.
What is papillary renal cell carcinoma?
Comprises 10%-15% of renal cancers, derived from the proximal convoluted tubule, showing a papillary growth pattern, often multifocal and bilateral.
What genetic mutation is associated with familial papillary renal cell carcinoma?
Increased dosage of the MET gene located on chromosome 7, due to trisomy or tetrasomy.
What is the morphology of papillary renal cell carcinoma?
Multifocal origin, less yellow than clear cell carcinoma, with papillae covered by eosinophilic cells arranged in a pseudostratified manner and a fibromuscular core
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