Skin + Kidney + Cardiac + RT Flashcards
(689 cards)
1
Q
Where do benign epithelial neoplasms develop from?
A
They develop from stem cells residing in the epidermis and hair follicles.
2
Q
Do benign epithelial neoplasms undergo malignant transformation?
A
Generally, they do not undergo malignant transformation.
3
Q
How does seborrheic keratosis present?
A
It presents as raised, round, discolored plaques on the extremities or face.
4
Q
What cells are involved in seborrheic keratosis?
A
It involves proliferating basal epidermal cells.
5
Q
What microscopic feature is characteristic of seborrheic keratosis?
A
Keratin pseudocysts on the epidermis, sometimes hyperkeratosis.
6
Q
Who is most commonly affected by seborrheic keratosis?
A
It is most common in the elderly.
7
Q
What is a rare but possible association with seborrheic keratosis?
A
In rare cases, it can appear as a paraneoplastic syndrome associated with GI tract carcinoma.
8
Q
What genetic mutation is involved in the pathogenesis of seborrheic keratosis?
A
Activating mutations in the Fibroblast Growth Factor receptor.
9
Q
What causes actinic keratosis?
A
It is usually a result of chronic exposure to sunlight.
10
Q
What is the risk associated with actinic keratosis?
A
It has the potential to become malignant (Squamous Cell Carcinoma - SCC).
11
Q
What genetic mutation is commonly associated with actinic keratosis?
A
TP53 mutation.
12
Q
How does actinic keratosis appear morphologically?
A
It is usually less than 1 cm in diameter, brown or red, and rough.
13
Q
What cytological features are seen in actinic keratosis?
A
Cytological atypia in the lower part of the epidermis and parakeratosis of the stratum corneum.
14
Q
Where do sebaceous adenomas typically appear?
A
In the head and neck region of older individuals.
15
Q
What do sebaceous adenomas look like?
A
They present as flesh-colored papules less than 5 mm.
16
Q
What syndrome is associated with sebaceous adenomas?
A
Muir-Torre syndrome.
17
Q
What internal malignancy is often associated with sebaceous adenomas?
A
Mainly colon carcinoma.
18
Q
What is the morphology of sebaceous adenomas? Histo
A
Lobular proliferation of sebocytes maintaining an organoid appearance with expansion of germinative basaloid cell layers at the periphery.
19
Q
What is squamous cell carcinoma?
A
Malignant proliferation of squamous cells.
20
Q
How does squamous cell carcinoma typically present?
A
As a red scaling nodular mass, usually on sun-exposed sites, commonly the face and lower lip.
21
Q
What are the risk factors for squamous cell carcinoma?
A
Sunlight exposure, albinism, xeroderma pigmentosum, immunosuppressive therapy, toxin exposure (arsenic), and chronic inflammation.
22
Q
What genetic mutations are involved in squamous cell carcinoma?
A
Mutations in TP53, HRAS, and loss of function in Notch receptors.
23
Q
How does squamous cell carcinoma affect the immune system?
A
It has an immunosuppressive effect on the skin by impairing antigen presentation by Langerhans cells.
24
Q
What are the morphological features of squamous cell carcinoma?
A
Atypical cells at all levels of the epidermis, invasive tumors penetrating the basement membrane, variable degrees of differentiation.
25
What is the treatment for squamous cell carcinoma?
Excision; rarely metastasizes, but the likelihood of metastasis relates to lesion thickness and invasion depth.
26
What is basal cell carcinoma?
Malignant proliferation of the basal cells of the epidermis.
27
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.
28
What genetic pathway is often mutated in basal cell carcinoma?
Mutations in the Hedgehog pathway and p53.
29
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.
30
What is the recommended treatment for basal cell carcinoma?
Radical removal to prevent extensive local invasion.
31
What is actinic keratosis a precursor lesion for?
Squamous cell carcinoma.
32
How does actinic keratosis present?
As a hyperkeratotic, scaly plaque, often on the face, back, or neck.
33
What is keratoacanthoma?
A well-differentiated squamous cell carcinoma that develops rapidly and regresses spontaneously.
34
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.
35
From where are melanocytes derived?
They are derived from the neural crest.
36
What precursor molecule is used by melanocytes to synthesize melanin?
Tyrosine is used as the precursor molecule to synthesize melanin in melanosomes.
37
To which cells do melanocytes pass melanosomes?
They pass melanosomes to keratinocytes.
38
What is a melanocytic nevus?
It is a benign tumor of melanocytes, also known as a nevus (congenital).
39
What is malignant melanoma?
It is a malignant tumor of melanocytes.
40
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.
41
What are junctional nevi?
They are initial nevi composed of oval cells that grow in nests along the dermoepidermal junction.
42
What are compound nevi?
They are junctional nevi that have grown into the underlying dermis as nests or cords of cells.
43
What are intradermal nevi?
In older lesions, the epidermal nests may be lost completely, leaving pure intradermal nevi.
44
What mutations are commonly found in benign nevi?
Activating mutations in BRAF, or less commonly in RAS.
45
What is the function of the BRAF gene?
The BRAF gene encodes a Ser/Thr kinase involved in directing cell growth.
46
What morphological changes occur in superficial nevus cells?
Superficial nevus cells are larger, less mature, tend to produce melanin, and grow in nests.
47
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.
48
What is a dysplastic nevus?
Dysplastic nevi consist mainly of compound nevi marked by cytological atypia with irregular nuclei and hyperchromasia.
49
What genetic mutations are associated with dysplastic nevi?
Mutations in BRAF or RAS.
50
How can dysplastic nevi occur?
They may occur sporadically or in a familial form (autosomal dominant inheritance).
51
What is the significance of familial dysplastic nevi?
They are considered markers for an increased risk of developing melanoma.
52
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.
53
Where do dysplastic nevi typically occur?
They can occur on both sun-exposed and non-exposed surfaces.
54
What pattern do nevus cells exhibit in dysplastic nevi?
Nevus cells exhibit a lentiginous pattern, replacing normal basal cells at the dermoepidermal junction.
55
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.
56
What is melanoma?
Malignant neoplasm of melanocytes and the most common cause of death from skin cancer.
57
What is the primary cause of melanoma?
Sunlight exposure.
58
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
59
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.
60
What mutations are common in sporadic melanomas?
Somatic activating mutations in the proto-oncogenes BRAF and NRAS.
61
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.
62
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.
63
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").
64
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.
65
What are the ABCs of melanoma?
Asymmetry, Border, Color, Diameter, Evolution (change of an existing nevus).
66
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.
67
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.
68
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.
69
Which type of nerve tumors belong to soft tissue tumors despite their derivation?
Tumors of the peripheral nerves, which are derived from the neuroectoderm.
70
From what do soft tissue tumors originate?
They originate from tissue-specific Mesenchymal stem cells (MSCs).
71
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.
72
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.
73
Where do 40% of soft tissue tumors occur?
40% of soft tissue tumors occur in the lower extremities.
74
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.
75
What diagnostic methods are important for classifying soft tissue tumors?
Histology, immunohistochemistry, electron microscopy, cytogenetics, and molecular genetics.
76
What are the characteristic histological patterns of soft tissue tumors?
Spindle cell, epithelioid, pleomorphic, small blue cell, biphasic
77
How is the grading of soft tissue tumors determined?
Grading is based on differentiation, mitotic activity, and the extent of necrosis.
78
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)
79
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.
80
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.
81
What is a lipoma?
A benign tumor of fat, most common in adults.
82
What are the characteristics of most lipomas?
They are solitary lesions, mobile, slowly enlarging, and painless masses.
83
What can multiple lipomas suggest?
Multiple lipomas may suggest the presence of rare hereditary syndromes.
84
What are conventional lipomas?
Soft, yellow, well-encapsulated masses of mature adipocytes, without pleomorphism.
85
What is a spindle cell lipoma?
A slow-growing subcutaneous tumor mainly found in the back, neck, and shoulders of older men.
86
What is a myolipoma?
A benign tumor consisting of fat cells with a variable number of muscle cells.
87
What is a myelolipoma?
A benign tumor composed of mature adipocytes and hematopoietic cells
88
What is a pleomorphic lipoma?
Characterized by giant cells resembling small flowers with overlapping nuclei.
89
What is an angiolipoma?
A subcutaneous nodule with vascular structures, commonly painful.
90
What is a liposarcoma?
A malignant neoplasm of adipocytes, usually occurring in individuals aged 50-60 years.
91
Where do most liposarcomas arise?
In deep soft tissues or the retroperitoneum.
92
What are well-differentiated liposarcomas?
Malignant lesions associated with amplification of a region in the long arm of chromosome 12.
93
What are dedifferentiated liposarcomas?
They consist of a well-differentiated liposarcoma adjacent to a more poorly differentiated tumor.
94
What are myxoid (round cell) liposarcomas?
Associated with translocation between chromosomes 12 and 16, affecting transcription factors in adipocyte differentiation.
95
What is the morphology of myxoid liposarcomas?
Characterized by an abundant mucoid extracellular matrix and the presence of lipoblasts indicating fatty differentiation.
96
What is nodular fasciitis?
A rapidly growing, self-limited fibroblastic proliferation, often resulting from trauma.
97
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.
98
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.
99
What are fibromatoses?
Benign soft tissue tumors that are locally aggressive but do not metastasize. They often recur after surgical removal.
100
What are superficial fibromatoses?
They arise in the superficial fascia and can be associated with trisomy 3 and 8.
101
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.
102
What is a fibrosarcoma?
A malignant neoplasm composed of fibroblasts, typically found in the deep tissues of the thigh, knee, and retroperitoneal area.
103
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.
104
What is the morphology of fibrosarcoma?
Soft, unencapsulated, infiltrative masses with areas of hemorrhage and necrosis, showing all degrees of differentiation on histologic examination.
105
T68 What are skeletal muscle neoplasms usually classified as?
They are almost all malignant.
106
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.
107
How can rhabdomyomas be classified?
They can be classified as adult type, fetal type, and genital type
108
What is the most frequent primary tumor of the heart in infants and children?
Rhabdomyoma
109
What is rhabdomyosarcoma?
A malignant neoplasm of skeletal muscle usually appearing in children and adolescents.
110
Where do rhabdomyosarcomas most commonly occur?
In the head and neck region or the urogenital tract.
111
What chromosomal translocation is often found in rhabdomyosarcoma?
The translocation t(2;13).
112
What are the morphological types of rhabdomyosarcoma?
Embryonal, alveolar, and pleomorphic variants.
113
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.
114
What is a rhabdomyoblast?
A cell that appears in all types of rhabdomyosarcoma, exhibiting granular, eosinophilic cytoplasm rich in thick and thin filaments.
115
What are the immunohistochemical markers for rhabdomyosarcoma?
Desmin and actin.
116
How is rhabdomyosarcoma typically treated in children?
With chemotherapy, which is often effective.
117
What is a leiomyoma?
A benign smooth muscle tumor, common and well-defined, most commonly arising in the uterus.
118
What chromosomal rearrangements are associated with leiomyomas?
Chromosomal rearrangements of chromosomes 6 and 12.
119
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.
120
What happens to large leiomyomas after menopause?
They may become collagenous and even calcified.
121
What is a leiomyosarcoma?
A malignant smooth muscle tumor that usually occurs in adults, more commonly in females, often as solitary tumors.
122
Where do leiomyosarcomas typically metastasize?
To the lungs.
123
How do leiomyosarcomas of the uterus usually arise?
De novo from mesenchymal cells of the myometrium, not from pre-existing leiomyomas.
124
What is the morphology of leiomyosarcomas?
They are soft, hemorrhagic, and necrotic with spindle cells, cigar-shaped nuclei, cytological atypia, and mitotic activity.
125
What differentiation is often seen in peripheral nerve tumors?
Evidence of Schwann cell differentiation.
126
What familial tumor syndromes are associated with peripheral nerve tumors?
Neurofibromatosis type 1 (NF1) and type 2 (NF2).
127
What is a schwannoma?
A benign, encapsulated tumor composed of Schwann cells, often causing local compression of the involved nerve or adjacent structures.
128
What genetic mutation is associated with NF2?
A dominant loss-of-function mutation of the merlin gene on chromosome 22.
129
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).
130
What is a neurofibroma?
A benign peripheral nerve sheath tumor.
131
What are the three types of neurofibromas?
Localized cutaneous, plexiform, and diffuse neurofibromas.
132
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.
133
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.
134
What is an MPNST?
A highly malignant sarcoma that is locally invasive and often shows evidence of Schwann cell derivation.
135
What percentage of MPNSTs arise from NF1?
50% of MPNSTs arise from NF1.
136
What is the morphology of MPNST?
Large, poorly defined tumor masses, highly cellular with anaplasia, necrosis, infiltrative growth pattern, pleomorphism, and high proliferative activity.
137
What causes NF1?
An autosomal dominant disorder caused by a mutation in the tumor suppressor neurofibromin on chromosome 17.
138
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.
139
What is the typical age range for synovial sarcoma patients?
20-40 years old.
140
Where do synovial sarcomas usually develop?
In deep soft tissues around large joints of the extremities, mainly the knee joint.
141
What chromosomal translocation is associated with synovial sarcoma?
t(X;18).
142
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).
143
Where do synovial sarcomas commonly metastasize?
To the lungs, bones, and regional lymph nodes.
144
T69 What is the functional unit of the kidney?
The nephron, composed of the glomerulus and a tubular system.
145
What is the glomerular capillary wall composed of?
Three layers: fenestrated endothelium, glomerular basement membrane, and visceral epithelium
146
What are the three sub-layers of the glomerular basement membrane?
Lamina rara interna, lamina rara externa, and lamina densa
147
What cells compose the visceral epithelium of the glomerular capillary wall?
Podocytes with interdigitating processes creating filtration slits.
148
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.
149
What factors determine the selective permeability of the glomerular filtration barrier?
The size and charge of the molecule, with cationic molecules being more permeable.
150
What is azotemia?
An elevation of blood urea nitrogen and creatinine levels, reflecting a decreased glomerular filtration rate (GFR).
151
What is prerenal azotemia?
Azotemia due to hypo perfusion of the kidney, resulting in decreased GFR
152
What is postrenal azotemia?
Azotemia due to urine flow obstruction below the level of the kidney.
153
What is uremia?
A condition where azotemia gives rise to clinical manifestations, with metabolic and endocrine alterations incident to renal damage.
154
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).
155
What characterizes nephritic syndrome?
Glomerular injury leading to hematuria, oliguria, azotemia, and hypertension.
156
What characterizes nephrotic syndrome?
Heavy proteinuria (>3.5g/day), hypoalbuminemia, severe edema, hyperlipidemia, and lipiduria.
157
What characterizes asymptomatic hematuria?
Non-nephrotic proteinuria, usually due to mild glomerular abnormalities.
158
What characterizes rapidly progressive glomerulonephritis?
Nephritic syndrome that progresses to renal failure in weeks to months.
159
What characterizes acute kidney injury?
Acute oliguria or anuria and azotemia, which may result from glomerular, interstitial, vascular, or tubular injury.
160
What characterizes chronic kidney disease?
Prolonged symptoms and signs of uremia due to progressive scarring in the kidney.
161
What characterizes urinary tract infection?
Bacteriuria and pyuria, which may be symptomatic or asymptomatic, affecting the kidney (pyelonephritis) or bladder (cystitis).
162
What characterizes nephrolithiasis?
Renal colic, hematuria without casts, and recurrent stone formation.
163
What are primary glomerular diseases?
Diseases where the kidney is the predominant organ involved.
164
What are secondary glomerular diseases?
Diseases caused by a systemic condition, such as SLE, hypertension, diabetes mellitus, or Alport syndrome.
165
What are the two types of immune reactions causing glomerular diseases?
Antibody-associated and cell-mediated.
166
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.
167
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.
168
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.
169
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.
170
What mediators are involved in immune injury of the glomerulus?
Complement-leukocyte mediated injury, monocytes and macrophages, platelets, resident glomerular cells, and thrombin.
171
What is podocyte injury?
Morphologic changes such as effacement of foot processes, vacuolization, retraction, and detachment of podocytes from the GBM, leading to proteinuria.
172
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.
173
T71 What characterizes nephrotic syndrome?
Proteinuria leads to hypoalbuminemia and edema, due to increased permeability of glomerular disorders.
174
What is massive proteinuria?
Daily protein loss in the urine of 3.5g or more.
175
What is hypoalbuminemia?
A serum albumin concentration of less than 3g/100 ml.
176
What is generalized edema?
Also called anasarca, results from decreased plasma oncotic pressure, often starting with periorbital edema.
177
What causes hyperlipidemia and lipiduria in nephrotic syndrome?
Increased hepatic lipoprotein synthesis, possibly triggered by hypoalbuminemia or massive proteinuria.
178
What causes the hypercoagulable state in nephrotic syndrome?
Loss of antithrombin III.
179
What is the primary cause of nephrotic syndrome in children
Primary illness, often idiopathic.
180
What is the primary cause of nephrotic syndrome in adults?
Usually a secondary manifestation of a systemic disease.
181
What are common secondary causes of nephrotic syndrome?
Diabetes and systemic amyloidosis.
182
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.
183
What is the pathogenesis of minimal-change disease?
Damage to podocyte foot processes caused by T-cell derived cytokines, leading to proteinuria.
184
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.
185
What are the clinical features of minimal-change disease?
Nephrotic syndrome without hypertension, preserved renal function, selective proteinuria (albumin), and good response to corticosteroids.
186
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.
187
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.
188
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.
189
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.
190
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.
191
What characterizes FSGS?
Sclerosis affecting some, but not all glomeruli (focal involvement) and involving only segments of each affected glomerulus (segmental involvement).
192
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.
193
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.
194
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.
195
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.
196
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.
197
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.
198
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.
199
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.
200
T70 What characterizes nephritic syndrome?
Glomerular inflammation, resulting in hematuria, oliguria, azotemia, and hypertension.
201
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.
202
What are oliguria and azotemia?
Oliguria is low urine output, and azotemia is high levels of nitrogen-containing compounds, both resulting from reduced GFR.
203
What causes hypertension in nephritic syndrome?
Fluid retention and release of renin from ischemic kidneys.
204
What are the histological features of nephritic syndrome?
Proliferation of glomerular cells and infiltration of inflammatory leukocytes.
205
What commonly causes acute postinfectious glomerulonephritis?
Develops following a streptococcal infection, typically beta-hemolytic group A strains.
206
What is the typical patient demographic for poststreptococcal glomerulonephritis?
Usually seen in children, but can also occur in adults.
207
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.
208
What are the hallmark lesions of PSGN? Acute Postinfectious Glomerulonephritis
Subepithelial "humps" seen in electron microscopy
209
What are the clinical features of poststreptococcal glomerulonephritis?
Fever, nausea, nephritic syndrome with mild oliguria, azotemia, hypertension, and gross hematuria (cola-colored urine).
210
What characterizes IgA nephropathy?
Deposition of IgA in the mesangium, causing recurrent microscopic or gross hematuria.
211
Who is most commonly affected by IgA nephropathy?
Children and young adults.
212
What triggers IgA nephropathy in genetically susceptible individuals?
Mucosal infections leading to increased and abnormal IgA production.
213
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.
214
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.
215
What causes hereditary nephritis?
Mutations in genes encoding GBM proteins, most commonly seen in Alport syndrome.
216
What is Alport syndrome?
A hereditary condition causing nephritis, sensory hearing loss, and eye disorders due to mutations in type IV collagen α chains.
217
What are the morphological features of Alport syndrome?
Early: Normal glomeruli. Late: Secondary sclerosis, foamy interstitial cells, GBM thinning, splitting, and lamination (basketweave appearance).
218
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.
219
220
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.
221
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.
222
What characterizes anti-GBM crescentic glomerulonephritis in immunofluorescence?
Linear deposits of IgG and C3 on the GBM.
223
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.
224
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.
225
What is the characteristic finding in immunofluorescence for immune-complex mediated crescentic glomerulonephritis?
Granular pattern of staining.
226
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.
227
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.
228
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.
229
What systemic vasculitis conditions may include crescentic GN as a component?
Microscopic polyangiitis (pANCA) and Wegener granulomatosis (cANCA).
230
What antibodies are typically found in pauci-immune crescentic glomerulonephritis?
Antineutrophil cytoplasmic antibodies (ANCA).
231
What distinguishes Churg-Strauss syndrome from other vasculitides?
Presence of eosinophilia, asthma, and granulomatous inflammation.
232
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).
233
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.
234
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.
235
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.
236
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.
237
What are the causes of acute tubular injury?
Ischemic injury, toxic substances (ethylene glycol, mercury, lead, carbon tetrachloride, methyl alcohol), and nephrotoxic drugs.
238
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.
239
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.
240
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.
241
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.
242
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.
243
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.
244
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.
245
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.
246
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.
247
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.
248
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.
249
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.
250
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.
251
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).
252
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.
253
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.
254
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.
255
What is hydronephrosis?
Dilation of the renal pelvis and calyces, with accompanying atrophy of the parenchyma, caused by obstruction to urine outflow.
256
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.
257
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.
258
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.
259
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).
260
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.
261
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.
262
T76 Urolithiasis, hydronephrosis, obstructive uropathy
263
T78 Diseases involving renal vessels, diabetic nephropathy
264
T77 What are small cortical papillary adenomas?
Benign tumors less than 0.5 cm in diameter, common and have no clinical significance.
265
What is the most common malignant tumor of the kidney?
Renal cell carcinoma, derived from renal tubular epithelium, primarily located in the cortex.
266
What are the common metastasis sites for renal cell carcinoma?
Lungs and bones.
267
What are the risk factors for renal cell carcinoma?
Smoking, obesity, hypertension, exposure to cadmium, and polycystic disease from chronic dialysis
268
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.
269
What are the three most common forms of renal cell carcinoma?
Clear cell carcinoma, papillary renal cell carcinoma, and chromophobe renal carcinoma.
270
What is clear cell carcinoma?
The most common type of renal cell carcinoma, derived from the proximal convoluted tubule, located predominantly in the cortex.
271
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.
272
What genetic mutation is associated with clear cell carcinoma?
Loss of VHL (chromosome 3) tumor suppressor gene, leading to increased IGF-1 and HIF.
273
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.
274
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.
275
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
276
What is chromophobe renal carcinoma?
The least common type of renal carcinoma (5%), arising from intercalated cells of the collecting ducts.
277
What is the morphology of chromophobe renal carcinoma?
Tan-brown gross appearance, tumor cells with abundant eosinophilic cytoplasm, distinct cell membranes, and nuclei surrounded by halos of clear cytoplasm.
278
Wilms Tumor (Nephroblastoma)
What is Wilms tumor?
A malignant mixed tumor containing metanephric blastema, stromal, and epithelial derivatives, most frequent in children before age 5.
279
Wilms Tumor (Nephroblastoma)
What genetic mutation is associated with Wilms tumor?
Mutations of the WT1 gene on chromosome 11 and nephroblastematosis.
280
What syndromes are associated with Wilms tumor?
WAGR syndrome (Wilms tumor, Aniridia, Genital abnormalities, Retardation) and Beckwith-Wiedemann syndrome (Wilms tumor, hypoglycemia, hemi hypertrophy, organomegaly).
281
What is the morphology of Wilms tumor?
Unilateral, encapsulated, and vascularized, with tumor epithelial components (abortive tubules and glomeruli), surrounded by metanephric blastema and immature spindled cell stroma.
282
What is urothelial carcinoma?
A malignant tumor arising from transitional epithelium, most common type of lower urinary tract cancer, usually arises in the bladder.
283
What are the risk factors for urothelial carcinoma?
Exposure to β-naphthylamine, cigarette smoking, chronic cystitis, schistosomiasis, and cyclophosphamide.
284
What are the pathways of urothelial carcinoma development?
Flat pathway: High-grade flat tumor invades, associated with early p53 mutations. Papillary pathway: Low-grade papillary tumor progresses to high-grade and then invades, not associated with early p53 mutations.
285
What is squamous cell carcinoma of the bladder?
A malignant proliferation of squamous cells, usually involving the bladder, arising in a background of squamous metaplasia.
286
What are the risk factors for squamous cell carcinoma of the bladder?
Chronic cystitis, Schistosoma hematobium infection, and long-standing nephrolithiasis.
287
What is adenocarcinoma of the bladder?
A malignant proliferation of glands, usually involving the bladder, arising from urachal remnants, cystitis glandularis, or bladder exstrophy.
288
What conditions are associated with adenocarcinoma of the bladder?
Urachal remnant, cystitis glandularis, and bladder exstrophy.
289
T79 What are the three subtypes of arteriosclerosis?
Atherosclerosis, Monckeberg's arteriosclerosis, and arteriolosclerosis.
290
What characterizes arteriolosclerosis?
Thickening of the intima affecting small arteries and arterioles, with two types: hyaline thickening and proliferative (hyperplastic) changes, usually associated with hypertension or diabetes mellitus.
291
What is Mönckeberg's arteriosclerosis?
Calcific deposits in the tunica media of medium-sized muscular arteries, not affecting blood flow as it does not involve the tunica intima.
292
What characterizes atherosclerosis?
Thickening and hardening of large to medium-sized arteries due to the accumulation of fatty material (cholesterol, TAGs).
293
What are common sites affected by atherosclerosis?
Abdominal aorta, coronary artery, popliteal artery, and internal carotid artery.
294
What is an atherosclerotic plaque/atheroma?
An intimal plaque that obstructs blood flow, consisting of a necrotic lipid core (mostly cholesterol) with a fibromuscular cap, often undergoing dystrophic calcification.
295
What complications can arise from atherosclerotic plaques?
Obstruction of blood flow, weakening of the underlying media, and rupture leading to acute thrombosis.
296
What are nonmodifiable risk factors for atherosclerosis?
Age, gender (pre-menopausal women have lower risk), and genetics (familial predisposition).
297
What are modifiable risk factors for atherosclerosis?
Hyperlipidemia (high LDL, low HDL), hypertension, cigarette smoking, diabetes mellitus, high levels of lipoprotein A, lack of exercise, stressful lifestyle, obesity, and hyperhomocystinemia.
298
How does hyperlipidemia contribute to atherosclerosis?
High LDL cholesterol delivers cholesterol to peripheral tissues, contributing to atheroma formation, while HDL mobilizes cholesterol for excretion, reducing risk.
299
How does hypertension contribute to atherosclerosis?
Both systolic and diastolic levels are important contributors to premature atherosclerosis.
300
How does cigarette smoking affect atherosclerosis?
Increases the incidence and severity of atherosclerosis; prolonged smoking increases the death rate from ischemic heart disease (IHD) by 200%.
301
How does diabetes mellitus contribute to atherosclerosis?
Induces hypercholesterolemia, increasing the risk of atheroma formation.
302
What is lipoprotein A and its role in atherosclerosis?
An altered form of LDL that increases the risk of coronary and cerebrovascular diseases, independent of cholesterol or LDL levels.
303
What is the response-to-injury hypothesis in atherosclerosis?
Atherosclerosis is a chronic inflammatory response of the arterial wall to endothelial injury, leading to the formation of raised lesions with a soft lipid core covered by a fibrous cap.
304
How does lesion progression occur in atherosclerosis?
Starts with endothelial damage, lipid leakage into the intima, oxidation of lipids, formation of foam cells by macrophages, and proliferation of smooth muscle and extracellular matrix deposition due to inflammation and healing processes.
305
What are fatty streaks in atherosclerosis?
Early lesions formed by lipid accumulation in the intima, visible as yellow streaks on the arterial walls.
306
What role do foam cells play in atherosclerosis?
Macrophages that have consumed oxidized lipids, contributing to the formation of the lipid core in atherosclerotic plaques.
307
What factors contribute to the inflammation and healing process in atherosclerosis?
Activated platelets, macrophages, and vascular wall cells release factors promoting smooth muscle proliferation and extracellular matrix deposition.
308
T80 What causes the formation of atherosclerotic intimal plaques?
Response to endothelial injury with chronic inflammation, involving lymphocytes and macrophages, and a fibroproliferative process with smooth muscle cells.
309
What are the early stages of atherosclerotic plaques?
Early stages include aggregates of foam cells (macrophages accumulating lipids) forming fatty streaks that progress to fibrofatty plaques with a fibrous cap and a lipid-laden core.
310
What can advanced atherosclerotic plaques lead to?
Plaque rupture (inducing thrombus formation), atheroembolism (plaque debris causing micro-emboli), aneurysm formation (weakening vessel wall), and critical stenosis (causing ischemic injury to organs).
311
What factors cause endothelial dysfunction leading to atherosclerosis?
Toxins from cigarette smoke, homocysteine, infectious agents, hemodynamic disturbances, and lipids (hypercholesterolemia).
312
How do hemodynamic disturbances contribute to atherogenesis?
Atherogenesis occurs at vessel openings, branch points, and along the posterior wall of the abdominal aorta where flow patterns are disturbed. Laminar flow induces protective gene expression.
313
How do lipids contribute to atherogenesis?
Hypercholesterolemia increases atherosclerosis risk. Accumulated lipoproteins in the intima are oxidized, ingested by macrophages through scavenger receptors, forming foam cells.
314
What role does inflammation play in atherogenesis?
Endothelial cells express adhesion molecules like VCAM-1, attracting monocytes and T cells. Macrophages engulf oxidized LDL, forming foam cells and producing cytokines that increase leukocyte adhesion and smooth muscle proliferation.
315
How does smooth muscle proliferation contribute to atherogenesis?
Smooth muscle proliferation and ECM deposition convert fatty streaks into mature atheromas. Smooth muscle cells produce collagen, stabilizing the plaque, and are derived from intima and circulating precursors.
316
What growth factors promote smooth muscle proliferation in atherogenesis?
Platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and transforming growth factor alpha (TGFα).
317
What are fatty streaks?
Lipid-filled macrophages (foam cells) that are not significantly raised, representing early atherosclerotic lesions
318
What is an atherosclerotic plaque?
Atheromatous plaques are white-yellow, may be hard and calcified, and consist of a fibrous cap, a necrotic core, and cholesterol clefts. They are commonly found in the abdominal aorta, coronary arteries, popliteal arteries, internal carotid arteries, and circle of Willis vessels.
319
What are the components of the fibrous cap in atherosclerotic plaques?
Smooth muscle cells and dense collagen.
320
What is found in the necrotic core of atherosclerotic plaques?
Intracellular and extracellular lipids, debris from dead cells, foam cells, and plasma proteins.
321
What is neovascularization in atherosclerotic plaques?
Proliferation of small blood vessels seen in the periphery of the plaque.
322
T81 What is hypertension?
Increased blood pressure, which may involve pulmonary or systemic circulation. Systemic hypertension is defined as blood pressure over 140/90 mm Hg.
323
What are the two main types of hypertension based on etiology?
Primary (essential) hypertension and secondary hypertension.
324
What factors contribute to hypertension?
Reduced renal Na+ excretion and vascular changes (vasoconstriction or structural changes in the vascular wall)
325
What is primary (essential) hypertension?
Hypertension of unknown etiology, accounting for about 95% of cases, involving inheritance and environmental factors.
326
What are the risk factors for primary hypertension?
Age, race (increased risk in African Americans, decreased risk in Asians), genetic factors (defects in RAS genes, family history), and environmental factors (stress, obesity, smoking, physical inactivity, heavy salt consumption).
327
What is secondary hypertension?
Hypertension secondary to a known underlying cause, such as renal artery stenosis or endocrine disorders.
328
How does renal artery stenosis cause hypertension?
Stenosis decreases blood flow to the glomerulus, causing renin secretion and activation of the renin-angiotensin-aldosterone system (RAAS), leading to increased blood pressure.
329
What endocrine disorders can cause secondary hypertension?
Conn syndrome (primary hyperaldosteronism), Cushing syndrome (excess cortisol), hyperthyroidism, and diabetes mellitus (complicated by diabetic glomerulonephritis).
330
What are the complications of hypertension?
Cardiac hypertrophy and heart failure, aortic dissection, renal failure, cerebrovascular hemorrhages, and hypertensive vascular disease.
331
What is hypertensive vascular disease?
Disease induced by hypertension, causing increased atherogenesis in large to medium-sized arteries, and two forms of small blood vessel diseases: hyaline arteriolosclerosis and hyperplastic arteriolosclerosis.
332
What is hyaline arteriolosclerosis?
Homogenous, pink proteinaceous thickening of arteriole walls with loss of structural detail and narrowing of the lumen, seen in hypertension and diabetes mellitus, leading to nephrosclerosis.
333
What is hyperplastic arteriolosclerosis?
Concentric, laminated thickening of arteriole walls ("onionskin" appearance) with luminal narrowing, associated with acute blood pressure elevations and accompanied by fibrinoid deposits and vessel wall necrosis.
334
What are the complications of hypertension in the heart and brain?
Heart: Progressive heart failure due to left ventricular hypertrophy.
Brain: Cerebrovascular stroke, Charcot-Bouchard aneurysms, cerebral hemorrhage, subarachnoid hemorrhage due to ruptured berry aneurysms
335
What are Charcot-Bouchard aneurysms?
Aneurysms of small brain vessels, often located in the lenticulostriate vessels of the basal ganglia, associated with chronic hypertension, and a common cause of cerebral hemorrhage.
336
What are berry aneurysms?
Small aneurysms that look like berries, occurring at cerebral artery departure points from the circle of Willis, frequently rupturing and bleeding in patients with benign hypertension.
337
What renal damage can hypertension cause?
Nephrosclerosis due to hyperplastic arteriolosclerosis, leading to renal damage.
338
T82 What is an aneurysm?
Localized abnormal balloon-like dilation of a blood vessel or the heart, which can lead to complications like thrombosis, embolization, and potential rupture.
339
What is the difference between a true aneurysm and a false aneurysm?
A true aneurysm involves all three layers of the arterial wall (e.g., atherosclerotic, syphilitic, congenital aneurysms). A false aneurysm (pseudoaneurysm) involves a breach in the vascular wall leading to an extravascular hematoma that communicates with the intravascular space.
340
What are the shapes and sizes of aneurysms?
Saccular aneurysm: Spherical outpouching involving a portion of the vessel wall, 5-20 cm in diameter.
Fusiform aneurysm: Circumferential dilation up to 20 cm in diameter, involving extensive portions of the aortic arch, abdominal aorta, and iliac artery.
341
What is a mycotic aneurysm?
An aneurysm caused by infection that weakens the wall of the artery, leading to rupture and thrombosis. Often results from endocarditis and septic emboli.
342
What are the causes of aortic aneurysms?
Inherited syndromes (e.g., Marfan syndrome, Ehlers-Danlos syndrome type 4), congenital conditions (e.g., bicuspid aortic valve), and acquired conditions (e.g., hypertension, atherosclerosis).
343
What is syphilitic aortitis?
An inflammation involving the vasa vasorum in the tertiary stage of syphilis, leading to hyperplastic thickening, ischemic medial injury, and aortic aneurysm.
344
How does atherosclerosis lead to abdominal aortic aneurysm (AAA)?
Severe atherosclerosis destroys and thins the aortic media, compromising nutrient and waste diffusion, causing medial degeneration, necrosis, and vessel dilation.
345
What are the two important variants of abdominal aortic aneurysm (AAA)?
Inflammatory AAA: Characterized by dense periaortic fibrosis with lymphocytes and macrophages infiltrate.
Mycotic AAA: Atherosclerotic lesions infected by circulating organisms due to bacteremia.
346
What is an aortic dissection?
A tear in the intima allowing blood to penetrate the aortic wall, creating an intramural hematoma that can rupture the aorta or propagate within the media.
347
What are the two main factors required for the development of an aortic dissection?
Very high pressure flow and preexisting weakness of the media layer.
348
What are the risk factors for aortic dissection
Men aged 40-60 with hypertension, and younger patients with connective tissue disorders (e.g., Marfan syndrome, Ehlers-Danlos syndrome).
349
Where is the typical tear found in an aortic dissection?
The tear is usually found in the ascending aorta within 10 cm of the aortic valve.
350
What is cystic medial degeneration (CMD)?
Separation of the elastic and smooth muscle cell elements of the media by cystic spaces filled with proteoglycan-rich extracellular matrix.
351
How are aortic dissections classified?
Proximal lesions (type A dissections) involve the ascending aorta (DeBakey type I).
Distal lesions (type B dissections) begin distal to the subclavian artery (DeBakey type III).
352
What are the clinical features of aortic dissection?
Sudden onset of excruciating pain, starting in the anterior chest, radiating to the back between the scapulae, and moving downward as the dissection progresses.
353
What are the complications of aortic dissection?
Cardiac tamponade, extension and compression of arterial outlets, and rupture into the mediastinum causing massive hemorrhage.
354
T83 What are varicose veins?
Abnormally dilated and tortuous veins, produced by prolonged increase in intramural pressure and loss of vessel wall support, usually affecting the superficial veins of the upper and lower leg.
355
What is the morphology of varicose veins?
Wall thinning at points of maximal dilation, smooth muscle hypertrophy, intimal fibrosis, elastic tissue degeneration, spotty medial calcifications (phlebosclerosis), and venous valve deformities.
356
What are the clinical features of varicose veins?
Venous valves become incompetent, leading to stasis and edema causing pain and thrombosis, persistent edema, secondary ischemic skin changes, stasis dermatitis, and chronic varicose ulcers.
357
What causes esophageal varices?
Portal vein hypertension, usually due to cirrhosis, portal vein obstruction, or hepatic vein thrombosis, leading to increased blood flow to gastro-esophageal veins.
358
What is a major complication of esophageal varices?
Rupture of esophageal varices can lead to massive upper GI hemorrhage that can be fatal
359
What causes hemorrhoids?
Varicose dilation of the hemorrhoidal venous plexus at the anorectal junction, caused by pregnancy, chronic constipation, or strain of defecation.
360
What is the difference between thrombophlebitis and phlebothrombosis?
Thrombophlebitis is an inflammation of the veins caused by a blood clot. Phlebothrombosis is the formation of blood clots in the veins.
361
What are the causes and risk factors for deep venous thrombosis (DVT)?
Stasis (e.g., bedridden patients), procoagulant state (e.g., contraceptives), and vascular wall injury (e.g., venipuncture, infection).
362
What are the symptoms of deep venous thrombosis (DVT)?
Local manifestations like distal edema, cyanosis, superficial vein dilation, and pain (e.g., Homan's sign), which can sometimes be absent.
363
What is the primary cause of pulmonary embolism?
95% of pulmonary embolisms result from deep venous thrombosis (DVT).
364
What causes superior vena cava (SVC) syndrome?
Neoplasms (e.g., bronchogenic carcinoma, mediastinal lymphoma) that compress or invade the SVC.
365
What are the symptoms of superior vena cava (SVC) syndrome?
Marked dilation of the veins of the head, neck, and arms, accompanied by cyanosis, and potentially respiratory distress from compressed pulmonary vessels
366
What causes inferior vena cava (IVC) syndrome?
Neoplasms (e.g., hepatocellular carcinoma, renal cell carcinoma), thrombi from hepatic, renal, or lower extremity veins, or other tumors compressing the IVC
367
What are the symptoms of inferior vena cava (IVC) syndrome?
Lower extremity edema, distension of superficial collateral veins of the lower abdomen, and massive proteinuria if renal veins are involved.
368
What are the types of vascular tumors?
Benign hemangiomas, intermediate lesions, and highly malignant angiosarcomas.
369
How do benign and malignant vascular tumors differ?
Benign tumors produce obvious vascular channels filled with blood cells, lined by a monolayer of normal endothelial cells. Malignant tumors are cellular with cytological anaplasia, and usually do not form well-organized vessels.
370
What is a hemangioma?
A common benign tumor of infancy and childhood characterized by an increased number of normal or abnormal blood vessels. It usually appears as a localized lesion on the skin, mucosa, or internal organs
371
What is a capillary hemangioma?
The most common type of hemangioma, consisting of closely packed thin capillaries and scant stroma, occurring in the skin, subcutaneous tissues, mucous membranes, liver, spleen, and kidneys.
372
What is a cavernous hemangioma?
Characterized by large vascular channels separated by connective tissue stroma, often involving deep structures like the liver, pancreas, spleen, and brain.
373
What is a glomus tumor (glomangioma)?
A benign, painful tumor arising from modified smooth muscle cells of the glomus body, commonly found under the fingernails.
374
What are vascular ectasias?
Local dilation of preexisting vessels, such as telangiectasia, nevus flammeus, and spider telangiectasia.
375
What is bacillary angiomatosis?
A reactive vascular proliferation due to opportunistic infection by Bartonella bacteria, commonly affecting immunocompromised individuals.
376
What is Kaposi sarcoma (KS)?
A vascular neoplasm developing from cells lining lymph or blood vessels, strongly associated with AIDS and caused by infection with human herpes virus 8 (HHV-8).
377
What are the types of Kaposi sarcoma?
Chronic (classic), lymphadenopathy (endemic African), transplant-associated, and AIDS-associated (epidemic) Kaposi sarcoma.
378
What are the stages of progression in Kaposi sarcoma?
Patches: Red-purple macules on distal extremities.
Plaques: Larger, raised lesions with dermal vascular channels.
Nodules: Nodular lesions with sheets of proliferating spindle cells.
379
What is angiosarcoma?
A malignant endothelial neoplasm, varying from well-differentiated to anaplastic, usually involving the skin, soft tissue, breast, and liver
380
What are the risk factors for hepatic angiosarcoma?
Exposure to carcinogens such as arsenic, thorium dioxide (thorotrast), and polyvinyl chloride.
381
What is a hemangiopericytoma?
A rare tumor derived from pericytes, most common on the lower extremities, consisting of numerous branching capillary channels and gaping sinusoidal spaces enclosed within nests of spindle-shaped cells.
382
T84 What is lymphangitis?
Lymphangitis is a bacterial infection of the lymphatic vessels, causing acute inflammation that spreads throughout the lymphatics.
383
What are the main causative agents of lymphangitis?
Group A, β-hemolytic streptococci, commonly caused by streptococcus or staphylococcus organisms.
384
What are the morphological changes in lymphangitis?
The affected lymphatics are dilated and filled with exudate of neutrophils and monocytes.
385
What are the clinical features of lymphangitis?
Visible red streaks under the skin extending from the infection site to the groin or armpit, with painful enlargement of the draining lymph nodes.
386
What can happen if bacteria in lymphangitis are not contained within the lymph nodes?
Bacteria may pass into the venous circulation, resulting in bacteremia or sepsis.
387
What is the major function of the lymphatic system?
To resorb fluid and protein from tissues and extravascular spaces.
388
What is unique about the permeability of lymphatic channels?
The absence of a basement membrane beneath lymphatic endothelial cells allows the resorption of proteins too large for venules.
389
What is the pathway for lymphatic drainage?
Lymph drains via afferent lymphatics to regional lymph nodes and then by efferent lymphatics to the cisterna chyli and the thoracic duct into the subclavian vein and venous circulation.
390
What is lymphedema?
Edema caused by impaired lymphatic drainage
391
What are the two forms of lymphedema?
Primary lymphedema (genetic) and secondary lymphedema (acquired defect in the lymphatic system).
392
What causes primary lymphedema?
Occurs as isolated congenital defect or as familial Milroy disease, often due to anaplastic lymphatic channels, manifesting from birth up to age 1 year due to lymphatic agenesis or hypoplasia.
393
What causes secondary lymphedema?
Accumulation of interstitial fluid due to blockage of normal lymph vessels, which can be caused by malignant tumors, therapeutic or post-inflammatory thrombosis, and scarring
394
What are common causes of secondary lymphedema?
Obesity, infection, neoplasm, trauma, and therapeutic modalities.
395
What is the most common cause of secondary lymphedema worldwide?
Filariasis, a disease caused by the parasite Wucheria bancrofti, transmitted by mosquitoes, causing lymph node infection and potentially leading to elephantiasis.
396
How does malignancy and cancer treatment cause secondary lymphedema?
Obstruction from metastatic cancer or primary lymphoma, radical lymph node dissection, and post-irradiation fibrosis can lead to lymphedema, commonly affecting the axillary region after mastectomy and dissection for breast cancer.
397
How does morbid obesity cause lymphedema?
Impairment of lymphatic return due to obesity commonly results in lymphedema.
398
What are the complications of lymphedema?
Increased hydrostatic pressure in lymph vessels causing accumulation of lymph fluid in various spaces, leading to chylous ascites (abdomen), chylothorax, and chylopericardium.
399
T85 What is heart failure?
Heart failure occurs when the heart is unable to pump blood at a rate necessary to supply the requirements of metabolizing tissues, leading to forward failure (inadequate cardiac output) and backward failure (increased venous congestion).
400
How does the cardiovascular system adapt to reduced myocardial contractility?
Activation of neurohumoral systems: release of epinephrine, activation of renin-angiotensin system, and release of atrial natriuretic peptide (ANP).
The Frank-Starling mechanism: increased EDV causes stretch of cardiac muscle fibers, resulting in more forceful contractions.
Myocardial structural changes: hypertrophy to increase contractile tissue mass.
401
What are the common causes of left-sided heart failure?
Ischemic heart disease (IHD), systemic hypertension, mitral or aortic valve disease, and primary diseases of the myocardium.
402
What are the morphological features of left-sided heart failure?
Hypertrophied and dilated left ventricle, secondary enlargement of the left atrium, pulmonary congestion and edema with interstitial transudate, alveolar septal edema, intra-alveolar edema, and heart failure cells (hemosiderin-laden macrophages)
403
What are the clinical features of left-sided heart failure?
Breathlessness (dyspnea), cough, orthopnea (dyspnea when lying down), enlarged heart, tachycardia, a third heart sound (S3), mitral regurgitation, and systolic murmur.
404
What are the common causes of right-sided heart failure?
Usually a consequence of left-sided heart failure. Isolated right-sided heart failure can occur due to intrinsic disease of lung parenchyma or pulmonary vasculature (cor pulmonale) or pulmonic/tricuspid valve disease
405
What are the morphological features of right-sided heart failure?
Liver congestion (nutmeg liver) with centrilobular necrosis and potential cardiac cirrhosis, congested enlarged spleen, fluid accumulation in pleural and pericardial spaces (effusion), and peripheral edema (pitting edema) in lower extremities.
406
What is cor pulmonale?
Right-sided heart failure resulting from intrinsic disease of lung parenchyma and/or pulmonary vasculature that causes chronic pulmonary hypertension.
407
What causes nutmeg liver in right-sided heart failure?
Chronic congestion of the liver due to elevated pressure in the hepatic venous system, leading to centrilobular necrosis and peripheral fatty change.
408
What are heart failure cells?
Macrophages containing hemosiderin, found in the lungs due to capillary leakage and breakdown of red blood cells in pulmonary congestion and edema.
409
What is a characteristic sign of peripheral edema in right-sided heart failure?
Pitting edema, symmetric in both lower extremities.
410
T86 What is ischemic heart disease (IHD)?
A group of related syndromes resulting from myocardial ischemia, commonly caused by atherosclerotic disease, increased demand, or diminished oxygen-carrying capacity.
411
What are the risk factors for developing ischemic heart disease (IHD)?
Age, gender, metabolic state, smoking, hypertension, anemia, and CO poisoning.
412
What are the clinical manifestations of ischemic heart disease (IHD)?
Angina pectoris, acute myocardial infarction, chronic IHD, and sudden cardiac death.
413
What is angina pectoris?
Periodic chest pain caused by reversible myocardial ischemia, characterized by pressing retrosternal pain not related to breathing, no elevation in myocardial enzymes, ECG changes, and relief with nitroglycerin.
414
What are the three variants of angina pectoris?
Typical (stable) angina
Prinzmetal (variant) angina
Unstable (crescendo) angina
415
What causes typical (stable) angina?
Episodic chest pain due to reversible injury to myocytes, often caused by fixed atherosclerotic narrowing (>70%) of coronary arteries, associated with increased myocardial oxygen demand.
416
How can typical (stable) angina be relieved?
Relieved by drugs that cause peripheral vasodilation, such as nitroglycerin.
417
What causes Prinzmetal (variant) angina?
Episodic chest pain at rest due to short-term complete occlusion of blood supply, often caused by coronary artery spasms or obstructive thrombus near an atherosclerotic plaque.
418
How can Prinzmetal (variant) angina be relieved?
Relieved by vasodilators such as nitroglycerin and calcium channel blockers.
419
What causes unstable (crescendo) angina?
Chest pain at rest from incomplete occlusion of coronary arteries, associated with atherosclerosis, plaque disruption, and thrombosis, with a high risk of progressing to myocardial infarction.
420
What is acute coronary syndrome?
A term referring to unstable angina, acute myocardial infarction, and sudden cardiac death, often associated with coronary thrombosis, embolism, or vasoconstriction.
421
What are the symptoms of acute coronary syndrome?
Severe angina pectoris, shortness of breath, nausea, sweating, and sympathetic dominance.
422
What are common causes of acute coronary syndrome?
Coronary thrombosis, embolism, acute plaque changes, vasoconstriction due to epinephrine, platelet release, endothelin, and cocaine usage.
423
T87 What is a myocardial infarction (MI)?
Necrosis of heart muscle resulting from ischemia, commonly known as a heart attack.
424
What is the major underlying cause of myocardial infarction (MI)?
Atherosclerosis, leading to plaque disruption and thrombogenesis.
425
What are the risk factors for myocardial infarction (MI)?
Hypertension, smoking, diabetes mellitus, gender (more common in men), age, and metabolic state.
426
What is the main cause of most myocardial infarctions (MIs)?
Acute coronary artery thrombosis due to disruption of an atherosclerotic plaque and thrombus formation
427
What usually causes subendocardial infarctions?
Increased demand such as arrhythmia or hypertension under settings of diffused coronary atherosclerosis, leading to ischemic necrosis of the myocardium most distal to the epicardial vessels.
428
What are some causes of myocardial infarction without occlusive atherosclerotic disease?
Vasospasms (Prinzmetal angina, elevated catecholamines, cocaine use), mural thrombus, valve vegetation leading to thromboembolism, and disorders of small intramyocardial arterioles (e.g., vasculitis, amyloid deposition, sickle cell disease).
429
What is the sequence of events in coronary artery occlusion leading to myocardial infarction?
Disruption of atheromatous plaque exposes subendothelial collagen and necrotic plaque to the blood.
Platelets aggregate and activate, releasing thromboxane A2, ADP, and serotonin, causing vasospasm.
Thrombus evolves to completely occlude the vessel.
430
What happens to myocardial cells during reversible and irreversible ischemia?
Reversible: Loss of contractility, myofibrillar relaxation, glycogen depletion, and cellular swelling.
Irreversible: Coagulation necrosis, leading to cell death.
431
What factors determine the location, size, and morphology of an infarct?
Size and duration of the involved vessel, rate of development, metabolic demands of the myocardium, and collateral circulation.
432
What are the common sites of infarcts in myocardial infarction?
Left anterior descending (LAD) artery (most common, 40%)
Right coronary artery (RCA, 2nd most common)
Left circumflex artery (LCX)
433
What are the stages of myocardial infarction?
First day: Coagulative necrosis, potential for arrhythmia and cardiogenic shock.
First week: Inflammation with neutrophil infiltration, risk of rupture.
End of month: Granulation tissue formation, leading to scar formation and potential aneurysm.
434
What are the clinical features of a myocardial infarction?
Severe chest pain radiating to neck, jaw, left arm, not relieved by nitroglycerin, rapid and weak pulse, nausea, dyspnea, and sympathetic dominance. In severe cases, cardiogenic shock may develop.
435
What is reperfusion injury and what causes it?
Injury that occurs when blood supply returns to the tissue after a period of ischemia, causing further damage due to free radicals and uncontrolled calcium influx, leading to contraction band necrosis
436
What are the lab findings indicative of myocardial infarction?
Elevated levels of myoglobin, cardiac troponin, creatine kinase, and LDH.
437
What are the possible consequences of a myocardial infarction?
Contractile dysfunction, arrhythmias, myocardial rupture, pericarditis, infarct expansion, mural thrombus, ventricular aneurysm, and papillary muscle dysfunction.
438
T88 What is hypertension?
A chronic medical condition in which the blood pressure in the arteries is elevated, requiring the heart to work harder than normal to circulate blood through the vasculature.
439
What factors regulate blood pressure?
Cardiac output (affected by blood volume) and total peripheral resistance (regulated by arterioles via neurological and hormonal inputs).
440
How do the kidneys regulate blood pressure?
The kidneys, along with the adrenal glands, regulate blood pressure mainly through the renin-angiotensin system (RAS).
441
What are some complications of hypertension?
Cardiac hypertrophy, heart failure (hypertensive heart disease), aortic dissection, and renal failure.
442
What is cardiac hypertrophy and why does it occur?
An increase in the mass and size of the heart due to increased work, as cardiac myocytes cannot undergo hyperplasia.
443
What are the two types of cardiac hypertrophy and their causes?
Concentric hypertrophy: Due to pressure overload (e.g., hypertension or aortic valve stenosis), characterized by increased wall thickness.
Eccentric hypertrophy: Due to volume overload (e.g., aortic valve insufficiency), characterized by ventricular dilation and muscle mass increase.
444
What can prolonged cardiac hypertrophy lead to?
Myocyte contractile failure, cardiac dilation, congestive heart failure (CHF), and sudden death.
445
What characterizes systemic hypertension in the heart?
Left ventricular hypertrophy without other cardiovascular pathology, and evidence of hypertension.
446
What is the morphology of the heart in systemic hypertension?
Left ventricular hypertrophy without dilation until late in the process. Heart weight ~500g, wall thickness >2cm, causing stiffness and impaired diastolic filling. Microscopically, nuclear enlargement, hyperchromasia, and interstitial fibrosis.
447
What defines pulmonary hypertension?
Pulmonary hypertension is characterized by increased pressure in the pulmonary circulation above 25 mmHg.
448
What are the pathological changes in pulmonary hypertension?
Atherosclerosis of the pulmonary trunk, smooth muscle hypertrophy of pulmonary arteries, intimal fibrosis, and plexiform lesions in severe cases.
449
What are the differences between primary and secondary pulmonary hypertension?
Primary: Seen in young adult females, often idiopathic or related to mutations in BMPR2.
Secondary: Due to hypoxemia (e.g., COPD, interstitial lung disease), increased pulmonary circuit volume (e.g., congenital heart disease), or recurrent pulmonary embolism.
450
What is cor pulmonale?
Enlargement and failure of the right ventricle due to increased vascular resistance or high blood pressure in the lungs.
451
What are common causes of cor pulmonale?
Primary disorders of the lung parenchyma or pulmonary vasculature, such as emphysema, interstitial pulmonary fibrosis, or primary pulmonary hypertension
452
How do acute and chronic cor pulmonale differ?
Acute: Follows massive pulmonary embolism with obstruction of >50% of the pulmonary vascular bed.
Chronic: Results from prolonged pressure overload due to pulmonary vasculature obstruction or septal capillary compression.
453
What is the morphology of the heart in acute and chronic cor pulmonale?
Acute: Right ventricle dilation without hypertrophy.
Chronic: Right ventricle hypertrophy, with dilation of the ventricle and right atrium if heart failure develops. Pulmonary arteries often contain atheromatous plaques.
454
T89 What is rheumatic fever?
An immunologically-mediated, systemic disease that occurs after group A, β-hemolytic streptococcus pharyngitis, usually 2-3 weeks after infection.
455
Which age group is most often affected by rheumatic fever?
Children aged 5-15 years old.
456
How can rheumatic fever be prevented?
By treating streptococcal throat infections with antibiotics like penicillin, preventing complications such as scarring of the mitral valve.
457
What is the pathogenesis of rheumatic fever?
It is a hypersensitivity reaction induced by host antibodies against group A streptococci, with some M proteins inducing antibodies that cross-react with glycoproteins in the heart and joints (molecular mimicry).
458
What is the classic lesion of rheumatic fever?
Aschoff body, an area of focal interstitial inflammation characterized by fragmented collagen, fibrinoid material, activated macrophages (Anitschkow cells), and occasional giant cells.
459
What are the major criteria in the Jones criteria for diagnosing rheumatic fever?
Polyarthritis
Pancarditis (endocarditis, myocarditis, pericarditis)
Subcutaneous nodules
Erythema marginatum
Sydenham's chorea
460
What is polyarthritis in the context of rheumatic fever?
A temporary migrating inflammation of the large joints, usually starting in the legs and migrating upwards.
461
What is pancarditis and its components in rheumatic fever?
inflammation of all three layers of the heart:
Endocarditis: small vegetations on valves, usually mitral.
Myocarditis: Aschoff bodies, common cause of death during acute phase.
Pericarditis: fibrinous exudate that resolves on its own.
462
What is erythema marginatum?
A reddish rash that begins on the trunk or arms as macules with clear centers, spreading outward and typically sparing the face.
463
What is Sydenham's chorea?
A series of involuntary rapid movements of the face and arms, characteristic of rheumatic fever.
464
What is rheumatic heart disease (RHD)?
A consequence of repeated inflammation of the endocardium due to recurrent rheumatic fever attacks, leading to fibrosis and scarring of the valves.
465
Which heart valves are commonly affected in rheumatic heart disease?
Mitral valve: stenosis and/or insufficiency.
Aortic valve: stenosis or insufficiency, usually along with the mitral valve.
Tricuspid valve: may be involved with the mitral and aortic valves.
Pulmonary valve: rarely involved.
466
What morphological changes occur in the valves in rheumatic heart disease?
Valve leaflets become thick, fibrotic, and deformed. Commissural fusion or shortening of cusps and thickening of chordae tendineae lead to abnormalities causing valve stenosis or regurgitation.
467
T90 What is valvular stenosis?
The failure of a valve to open completely, obstructing forward flow, usually caused by chronic processes like calcification or valve scarring.
468
What is valvular insufficiency?
The failure of the valve to close completely, allowing backflow, resulting from either intrinsic disease of the valve cusps or distortion of the supporting structures such as chordae tendineae or papillary muscles.
469
Which valve is most often affected by valvular disease?
The mitral valve.
470
What causes abnormal heart sounds (murmurs) in valvular disease?
The abnormal flow through diseased valves.
471
What are some causes of valvular disease?
Congenital disorders or acquired diseases such as rheumatic heart disease, infective endocarditis, and calcification (aortic valve).
472
What is calcific aortic stenosis?
The most common degenerative valvular disease and the most frequent cause of aortic stenosis, typically due to age-associated calcification.
473
What are the risk factors for calcific aortic stenosis?
Same as those for atherosclerosis, including age-related wear and tear.
474
What is the morphology of calcific aortic stenosis?
Nodular calcified masses on the outflow side of the cusps causing them to protrude into the aortic sinuses, obstructing normal opening without commissure fusion.
475
What is the significance of a bicuspid aortic valve?
It is a congenital valve defect (1% of live births) with increased risk of developing aortic calcification stenosis earlier.
476
What is mitral valve prolapse?
Characterized by myxoid (mucoid) degeneration of one or both leaflets of the mitral valve, causing them to become floppy and push back into the left atrium during systole.
477
In which gender is mitral valve prolapse more frequently seen?
Women.
478
What is the morphology of mitral valve prolapse?
Affected leaflets are enlarged, thick, and rubbery; chordae tendineae are elongated, thin, and may be ruptured. Histologically, there is increased deposition of mucoid material in the spongiosa layer.
479
What is the primary and secondary cause of mitral valve prolapse?
Primary cause is unknown, but may be associated with intrinsic defects of connective tissue (e.g., Marfan syndrome, Ehlers-Danlos syndrome). Secondary causes include ischemic dysfunction
480
What are the clinical features of mitral valve prolapse?
Most patients are asymptomatic, but it may cause palpitations, breathlessness, and atypical chest pain. It can be heard as a murmur in the middle of systole.
481
What are the complications of severe mitral valve prolapse?
Severe mitral regurgitation leading to left-sided congestive heart failure, increased risk for ventricular arrhythmias, and increased risk for infective endocarditis on the injured valve.
482
T91 What is endocarditis?
Endocarditis is the inflammation of the endocardium, the inner layer of the heart, usually involving the heart valves.
483
What other structures, besides the heart valves, can be involved in endocarditis?
The interventricular septum and the chordae tendineae.
484
What characterizes endocarditis?
Abnormal growth of the endocardium, composed of platelets, fibrin, microcolonies of microorganisms, and inflammatory cells.
485
What is infective endocarditis?
It is an infection of the endocardial surface of the heart characterized by microbial invasion of heart valves or mural endocardium, often including destruction of the underlying tissue.
486
What are most cases of infective endocarditis caused by
Extracellular bacteria.
487
What are the two types of infective endocarditis?
Acute endocarditis and subacute endocarditis.
488
What characterizes acute endocarditis?
A destructive infection caused by a highly virulent organism (e.g., Staphylococcus aureus) that attacks a previously normal valve.
489
What characterizes subacute endocarditis?
Infections by organisms of low virulence (e.g., Streptococcus viridans) colonizing a previously abnormal heart, especially deformed valves.
490
What are the morphological features of infective endocarditis?
Destructive vegetations on heart valves containing fibrin, inflammatory cells, and microorganisms. These can penetrate into the myocardium to produce abscess cavities and may lead to systemic emboli.
491
What cardiac abnormalities predispose individuals to infective endocarditis?
Rheumatic heart disease, mitral valve prolapse, bicuspid aortic valve, and calcific valvular stenosis.
492
What are the clinical features of infective endocarditis?
Fever, fatigue, flu-like syndrome, splenomegaly in subacute cases, rapidly developing fever, chills, weakness, fatigue, and murmurs in left-sided abnormalities. Diagnosis is based on positive blood cultures and echocardiography.
493
What are the complications of infective endocarditis?
Glomerulonephritis, septicemia, arrhythmias, and systemic embolization.
494
Non-bacterial Thrombotic Endocarditis (NBTE)
What characterizes NBTE?
Deposition of sterile thrombotic masses composed mainly of fibrin and platelets on heart valves, usually found on previously normal valves.
495
What conditions typically cause NBTE?
Hypercoagulative states (e.g., DIC), hyperestrogenic states, or underlying malignancy (e.g., adenocarcinomas).
496
What are the clinical features of NBTE?
Embolization may occur to the brain and heart, and it may serve as a surface for infective agents to implant.
497
What is Libman-Sacks endocarditis?
Sterile vegetations that develop on the valves of patients with SLE, resulting from immune complex deposition and potentially leading to valve deformities.
498
What are the two types of prosthetic valves?
Mechanical valves and bioprosthetic valves.
499
What are the characteristics of mechanical valves?
Made of pyrolytic carbon, have excellent durability, require chronic anticoagulation treatment, and can cause hemolysis due to shear stress.
500
What are the characteristics of bioprosthetic valves?
Made from porcine, bovine, or human tissues, do not require anticoagulation, less durable, can fail due to matrix deterioration, and may cause stenosis due to stiffening and calcification.
501
What is the risk of infection in prosthetic valves?
In mechanical valves, infective endocarditis usually involves the suture line and adjacent perivalvular tissue, while in bioprosthetic valves, both the valve and surrounding tissue can be infected, commonly by Staphylococcus epidermidis.
502
T92 What is myocarditis?
Myocarditis is the inflammation of the myocardium resulting from an infective agent or an inflammatory process that causes myocardial injury.
503
What are the common causes of myocarditis?
Infections (viruses like Coxsackieviruses A and B, CMV, bacteria like Lyme disease Borrelia burgdorferi, fungi like Candida, and protozoa like Trypanosoma in Chagas disease) and non-infectious causes (systemic immune diseases like SLE and polymyositis).
504
What are the macro and micro morphological features of myocarditis?
Macro: The heart may appear normal or dilated, with patchy pallor and/or hemorrhage.
Micro: Edema, interstitial inflammatory infiltrate with signs of myocyte injury, including lymphocytic, hypersensitivity (eosinophils), giant-cell, and Chagas myocarditis (trypanosomes in myofibers).
505
What are the clinical features of myocarditis?
Symptoms can range from asymptomatic to severe heart failure or arrhythmias, including fatigue, dyspnea, palpitations, pain, and fever.
506
What are cardiomyopathies?
Cardiomyopathies are diseases of the heart muscle characterized by intrinsic myocardial dysfunction, including dilated, hypertrophic, and restrictive types.
507
What is the difference between primary and secondary cardiomyopathies?
Primary: Disease mostly confined to the heart muscle.
Secondary: Heart involvement as part of a general, multi-organ disorder.
508
What characterizes dilated cardiomyopathy?
Progressive cardiac dilation and contractile dysfunction, usually accompanied by hypertrophy.
509
What are the causes of dilated cardiomyopathy?
Idiopathic (unknown), genetic (autosomal dominant), toxic (alcohol), myocarditis, and pregnancy-associated changes.
510
What are the clinical features of dilated cardiomyopathy?
Slowly progressive congestive heart failure, ineffective contraction, ejection fraction <25%, secondary mitral regurgitation, and abnormal cardiac rhythms.
511
What characterizes hypertrophic cardiomyopathy?
Myocardial hypertrophy, abnormal diastolic filling, and in some cases, ventricular outflow obstruction.
512
What are the genetic causes of hypertrophic cardiomyopathy?
Autosomal dominant mutations in genes encoding sarcomere proteins, commonly β-myosin heavy chain, myosin-binding protein C, and troponin T.
513
What are the morphological features of hypertrophic cardiomyopathy?
Massive myocardial hypertrophy without ventricular dilation, banana-like ventricular cavity, and asymmetrical septal hypertrophy.
514
What are the clinical features of hypertrophic cardiomyopathy?
Impaired diastolic filling, reduced stroke volume, dyspnea, systolic ejection murmur, atrial fibrillation, infective endocarditis of the mitral valve, chronic heart failure, arrhythmias, and sudden death.
515
What characterizes restrictive cardiomyopathy?
Primary decrease in ventricular compliance, impaired ventricular filling during diastole, normal left ventricular contractile function, and bi-atrial dilation.
516
What are the causes of restrictive cardiomyopathy?
Idiopathic or associated with systemic diseases affecting the myocardium, such as fibrosis (post-radiation), amyloidosis, hemochromatosis, and sarcoidosis.
517
What are the specific forms of restrictive cardiomyopathy?
Endomyocardial fibrosis (common in tropical countries), Löffler endomyocarditis (with mural thrombi), and amyloidosis (extracellular protein deposits).
518
T93 What are congenital heart diseases?
Congenital heart diseases are abnormalities of the heart or great vessels that are present at birth, most of which arise during weeks 3-8 of gestation when major cardiovascular structures develop.
519
What are the major causes of congenital heart disease?
Most cases (~90%) are of unknown cause. Environmental factors include congenital rubella infection and teratogen exposure. Genetic factors include familial forms and chromosomal abnormalities (trisomies 13, 15, 18, 21, and Turner syndrome). Mutations in transcription factors (TBX5, NKX2.5) and abnormal neural crest cell development (deletions in chromosome 22) can also cause defects.
520
What are the three main types of congenital heart disease based on their effects?
Malformations causing a left-to-right shunt.
Malformations causing a right-to-left shunt.
Malformations causing obstruction.
521
What are the effects of left-to-right shunts?
Left-to-right shunts increase pulmonary blood flow, resulting in right ventricular hypertrophy and eventually right-sided heart failure. They are not associated with early cyanosis but can lead to pulmonary hypertension and cyanosis over time.
522
What are the three types of atrial septal defects?
Ostium secundum ASD – most common (90%), occurs when the septum secundum does not sufficiently cover the ostium secundum.
Ostium primum ASD – less common (5%), associated with endocardial cushion defects.
Sinus venosus ASD – less common (5%), located near the entrance of the superior vena cava.
523
What are the characteristics of ventricular septal defects?
Incomplete closure of the ventricular septum leading to left-to-right shunts. Most (90%) are in the membranous septum, with the rest in the muscular septum. Larger defects cause severe shunts and can lead to pulmonary hypertension and heart failure.
524
What is a patent ductus arteriosus?
PDA is a condition where the ductus arteriosus remains open after birth, allowing blood to flow from the aorta to the pulmonary artery. This causes volume overload, pulmonary hypertension, and can lead to right heart hypertrophy and heart failure.
525
What are the effects of right-to-left shunts?
Right-to-left shunts cause early cyanosis as poorly oxygenated blood is introduced into the systemic circulation. They are associated with severe systemic cyanosis, polycythemia, and risk of paradoxical embolism.
526
What are the four features of Tetralogy of Fallot?
Ventricular septal defect (VSD).
Obstruction to right ventricular outflow (pulmonary stenosis).
An aorta that overrides the VSD.
Right ventricular hypertrophy.
527
What is the transposition of the great vessels ?
A congenital defect where the aorta arises from the right ventricle and the pulmonary trunk from the left ventricle, leading to separation of systemic and pulmonary circulations. Requires a VSD, ASD, or PDA for survival.
528
What are common congenital obstructive lesions?
Pulmonic valve stenosis, aortic valve stenosis, and coarctation of the aorta.
529
What are the two forms of coarctation of the aorta?
Infantile – hypoplasia of the aortic arch proximal to a patent ductus arteriosus, causing right ventricular hypertrophy.
Adult – ridge-like infolding of the aorta opposite the ligamentum arteriosum, causing left ventricular hypertrophy and potential atherosclerosis.
530
What are the clinical features of atrial septal defects (ASD)?
ASDs are initially asymptomatic in childhood but can lead to pulmonary hypertension, right ventricular hypertrophy, and eventual right-to-left shunt with cyanosis.
531
What are the clinical features of ventricular septal defects (VSD)?
Small VSDs are asymptomatic, while larger defects cause severe left-to-right shunts, pulmonary hypertension, and congestive heart failure; progressive pulmonary hypertension can lead to reversal of the shunt and cyanosis.
532
What are the clinical features of patent ductus arteriosus (PDA)?
PDAs are high-pressure shunts, audible as "machinery-like" murmurs; large defects can lead to Eisenmenger syndrome with cyanosis and congestive heart failure.
533
T94 What are the key characteristics and spirometry changes in obstructive pulmonary diseases?
Characteristics: Limitation of airflow due to anatomic airway narrowing or loss of elastic recoil.
Spirometry Changes: Decreased expiratory flow rate (FEV1), decreased forced vital capacity (FVC), increased total lung capacity (TLC). FEV1/FVC ratio < 0.8.
Examples: Emphysema, chronic bronchitis, bronchiectasis, asthma.
534
What are the key characteristics and spirometry changes in restrictive pulmonary diseases?
Characteristics: Reduced expansion of lung parenchyma, decreased total lung capacity.
Spirometry Changes: Reduced FVC, normal or proportionally reduced FEV1. FEV1/FVC ratio near normal.
Examples: Interstitial lung disease, idiopathic pulmonary fibrosis, chest wall disorders.
535
What is the general definition and key differentiator of COPD compared to asthma?
Definition: Group of diseases characterized by irreversible airflow obstruction, includes chronic bronchitis and emphysema.
Key Differentiator: Unlike asthma, which has reversible airflow obstruction, COPD is characterized by irreversible airflow obstruction.
536
What is emphysema and how is it characterized?
Definition: Permanent enlargement of the airspaces due to destruction of alveoli walls.
Characterization: By the loss of elastic tissue in the surrounding alveolar septa, leading to airway collapse during expiration and chronic airflow obstruction.
537
What are the types of emphysema and their characteristics?
Centriacinar Emphysema:
Common in smokers without α1-antitrypsin deficiency.
Affects proximal parts of acini, primarily in upper lobes.
Panacinar Emphysema:
Associated with α1-antitrypsin deficiency.
Uniformly enlarged acini, primarily in lower lobes.
Distal Acinar (Paraseptal) Emphysema:
Proximal acinus normal, distal part affected.
Near pleura, scarring, or atelectasis; may form bullae.
Irregular Emphysema:
Clinically asymptomatic, associated with scarring.
538
Centriacinar Emphysema:
Common in smokers without α1-antitrypsin deficiency.
Affects proximal parts of acini, primarily in upper lobes.
539
Panacinar Emphysema
Associated with α1-antitrypsin deficiency.
Uniformly enlarged acini, primarily in lower lobes.
540
Distal Acinar (Paraseptal) Emphysema
Proximal acinus normal, distal part affected.
Near pleura, scarring, or atelectasis; may form bullae.
541
Irregular Emphysema
Clinically asymptomatic, associated with scarring
542
What is the pathogenesis of emphysema
1. Protease/Antiprotease Imbalance:
Exposure to toxic substances (e.g., tobacco smoke) induces inflammation with accumulation of neutrophils, macrophages, and lymphocytes.
Neutrophils release elastase, and smoking increases elastase activity, reducing α1-antitrypsin's effectiveness.
Deficiency of α1-antitrypsin, especially in individuals homozygous for the PiZ allele, results in unchecked protease activity and alveolar destruction.
2. Oxidant/Antioxidant Imbalance:
Increased free radicals from smoking deplete lung antioxidants, contributing to tissue damage.
543
Describe the morphology of emphysema.
Macro: Pale, overinflated lungs (panacinar), deeper pink, less volume (centriacinar).
Micro: Destruction of alveolar walls without fibrosis, leading to enlarged air spaces.
544
What are the clinical features of emphysema?
Dyspnea, prolonged expiration with pursed lips, weight loss, barrel chest, "pink puffer" appearance.
Spirometry shows decreased FEV1, reduced FEV1/FVC ratio.
545
What is asthma and its hallmarks?
Definition: Chronic inflammatory disorder with reversible airway obstruction due to bronchoconstriction.
Hallmarks: Chronic bronchial inflammation with eosinophils, bronchial smooth muscle cell hypertrophy and hyperreactivity, increased mucus secretion.
546
What are the types of asthma?
1.Atopic (Extrinsic) Asthma:
IgE-mediated (type I hypersensitivity), associated with family history of allergies.
2. Non-atopic (Intrinsic) Asthma:
Triggered by infections or pollutants, not IgE-mediated.
3. Drug-Induced Asthma:
Triggered by drugs like aspirin.
4. Occupational Asthma:
Triggered by workplace antigens.
547
Describe the pathogenesis of asthma.
- Initial Sensitization: Allergen exposure activates TH2 cells, leading to IgE production and mast cell sensitization.
- Re-exposure: Mast cell degranulation releases histamine and leukotrienes, causing bronchoconstriction and inflammation.
- Late Phase Reaction: Eosinophils release major basic protein, causing epithelial damage and maintaining bronchoconstriction.
548
What are the morphological features of asthma?
Macro: Overdistended lungs, small areas of atelectasis, mucous plugs.
Micro: Curschmann spirals, eosinophils, Charcot-Leyden crystals, airway remodeling (thickening, fibrosis, increased vascularity, muscle hypertrophy
549
What are the clinical features of asthma?
Episodes of wheezing, breathlessness, chest tightness, and cough.
Difficult expiration leading to hyperinflation.
Management includes bronchodilators and corticosteroids
550
What defines chronic bronchitis, and who is most commonly affected?
Definition: Chronic inflammation of the mucous membranes of the bronchi, characterized by a persistent productive cough for at least 3 consecutive months in at least 2 consecutive years.
Commonly Affected: Smokers and urban/city residents, typically aged 40-65.
551
What are the three forms of chronic bronchitis?
1. Simple Chronic Bronchitis: Most common type, characterized by a productive cough without airway obstruction.
2. Chronic Asthmatic Bronchitis: Hyperresponsive airways with bronchospasms leading to asthma episodes.
3. Chronic Obstructive Bronchitis: Found in heavy smokers, characterized by outflow obstruction, usually associated with emphysema.
552
Describe the pathogenesis of chronic bronchitis.
- Hypersecretion of Mucus: Due to irritation from smoking or pollutants, leading to hypertrophy and hyperplasia of bronchial mucous glands.
- Inflammation: Caused by irritants, leading to the accumulation of cytotoxic T cells, macrophages, and neutrophils (no eosinophils).
- Peripheral Airflow Obstruction: Resulting from goblet cell metaplasia, mucus plugging, inflammation, bronchiolar wall fibrosis, and coexistent emphysema.
- Microbial Infection: Often present, maintaining inflammation and exacerbating symptoms.
553
What is the morphology of chronic bronchitis?
Macro: Mucosal lining is hyperemic and swollen with edema, covered by mucinous or mucopurulent secretion.
Micro: Enlargement of mucous-secreting glands in the trachea and large bronchi, inflammatory infiltration of mononuclear cells.
Bronchiolitis: Small airway disease characterized by goblet cell metaplasia, fibrosis, inflammation, and mucus plugging.
Severe Cases: Complete obliteration of the lumen due to fibrosis (bronchiolitis obliterans), leading to luminal narrowing and airway obstruction. Often coexists with emphysema.
554
What are the clinical features of chronic bronchitis?
Early Stage: Productive cough without airway obstruction or ventilation problems.
Advanced Stage: Significant COPD with outflow obstruction, leading to cyanosis ("blue bloaters").
555
What is bronchiectasis, and what are its common causes?
Definition: Abnormal permanent dilation of the bronchi due to chronic necrotizing infections, causing loss of muscle and elastic tissue.
Causes: Congenital (cystic fibrosis, Kartagener syndrome, immunodeficiency states) or acquired (post-infectious, autoimmune diseases, bronchial obstruction by foreign bodies or tumors).
556
What conditions predispose to bronchiectasis?
1. Tumors/Foreign Bodies: Leading to localized bronchiectasis.
2. Cystic Fibrosis (CF): Causing widespread bronchiectasis due to abnormally viscid mucus.
Immunodeficiency States: Leading to repeated bacterial infections.
3. Kartagener Syndrome: An autosomal recessive disorder causing immotile cilia and impaired mucociliary clearance, leading to infections.
4. Necrotizing/Suppurative Pneumonia: Especially due to Staphylococcus aureus and Klebsiella species, which may lead to post-infectious bronchiectasis.
557
Describe the pathogenesis of bronchiectasis.
Chronic Persistent Infection: Direct damage to the bronchial wall or
Obstruction: Impairs airway clearance, leading to secondary infection.
Host Response: Neutrophilic proteases, inflammatory cytokines, nitric oxide, and other factors cause damage to the muscular and elastic components of the bronchial wall and peribronchial alveolar tissue, resulting in bronchial dilatation and bronchial wall destruction.
558
What is the morphology of bronchiectasis?
Macroscopic: Focal process involving lobes or segments of the lung, or a diffuse process (e.g., CF bronchiectasis). Irregular lung surface with multiple cavities/cystic formations (dilated bronchi) of varying sizes, thick fibrous walls, and mucopurulent content.
Microscopic: Chronic inflammation, ulceration, intense inflammatory exudate, fibrosis, and scarring of bronchial and peribronchial walls. In severe cases, fibrosis leads to abnormal dilation and scarring.
559
What are the clinical features of bronchiectasis?
Symptoms: Severe, persistent cough with mucopurulent sputum (may contain blood), hypoxemia, hypercapnia.
Chronic Complications: Pulmonary hypertension or cor pulmonale (though rare).
560
T96 What is Acute Respiratory Distress Syndrome (ARDS)?
ARDS is a clinical syndrome caused by diffuse alveolar capillary and epithelial damage, leading to rapid onset of severe, life-threatening respiratory insufficiency, cyanosis, and severe arterial hypoxemia. It is characterized by deficient oxygenation of the blood and usually severe pulmonary edema.
561
What are the most common causes of ARDS?
The most common causes of ARDS are pneumonia and aspiration of gastric contents. Other causes include sepsis, shock (e.g., burns), diffuse pulmonary infections (viral, mycoplasma, Pneumocystis, tuberculosis), mechanical trauma, and inhaled irritants or chemical injury.
562
Describe the pathogenesis of ARDS
ARDS is due to widespread damage to the alveolar barrier. Damage to capillary endothelium and alveolar epithelium leads to increased capillary permeability, resulting in accumulation of protein-rich fluid inside the alveoli, alveolar edema, loss of diffusion capacity, and surfactant abnormalities (due to damage to type II pneumocytes).
This produces diffuse alveolar damage, with release of pro-inflammatory cytokines (IL-8, IL-1, TNF) by pulmonary macrophages, leading to recruitment of neutrophils, and activation of endothelium. Neutrophils release toxic mediators (reactive oxygen species, proteases), causing oxidative cell damage.
563
What is the morphology of ARDS in the acute phase?
In the acute phase of ARDS, the lungs are dark red, firm, airless, and heavy. There is capillary congestion, necrosis of alveolar epithelium, interstitial and intra-alveolar edema, neutrophils in capillaries (especially in sepsis), and hyaline membranes line the distended alveolar ducts.
564
What changes occur during the organized phase of ARDS?
In the organized phase of ARDS, there is increased proliferation of type II pneumocytes attempting to regenerate the alveolar lining. There is also organization of fibrin exudates leading to intra-alveolar fibrosis (resulting in "honeycomb lung") and thickening of alveolar septa.
565
What are the clinical features of ARDS?
ARDS develops within 72 hours from the initial insult and has high mortality rates, especially if related to sepsis and development of multiorgan failure.
566
What is atelectasis?
Atelectasis is the loss of lung volume caused by inadequate expansion of airspaces or collapse of previously inflated lung. It results in shunting of inadequately oxygenated blood from pulmonary arteries into the pulmonary veins, leading to ventilation-perfusion imbalance and hypoxia.
567
Describe the three types of atelectasis.
1. Resorption Atelectasis: Occurs when obstruction prevents air from reaching the distal airways, most commonly by mucous or mucopurulent plugs. The level of obstruction determines the extent of the collapse. The air already present is gradually absorbed, leading to alveolar collapse.
2. Compression Atelectasis: Associated with accumulations of fluids, blood, or air (pneumothorax) within the pleural cavity, which mechanically collapse the adjacent lung.
3. Contraction Atelectasis: Occurs when local or generalized fibrotic changes in the lung or pleura prevent expansion and cause increased elastic recoil during expiration.
568
Resorption Atelectasis
Occurs when obstruction prevents air from reaching the distal airways, most commonly by mucous or mucopurulent plugs. The level of obstruction determines the extent of the collapse. The air already present is gradually absorbed, leading to alveolar collapse.
569
Compression Atelectasis
Associated with accumulations of fluids, blood, or air (pneumothorax) within the pleural cavity, which mechanically collapse the adjacent lung.
570
Contraction Atelectasis
Occurs when local or generalized fibrotic changes in the lung or pleura prevent expansion and cause increased elastic recoil during expiration.
571
T97 What is Respiratory Distress Syndrome of the Newborn (RDS)?
RDS is a syndrome affecting premature infants caused by developmental insufficiency of surfactant production and structural immaturity of the lungs. It occurs in approximately 60% of infants born at less than 28 weeks of gestation and is associated with maternal diabetes mellitus and cesarean section.
572
What is the pathogenesis of RDS in newborns?
The fundamental defect in RDS is the inability of the immature lung to synthesize surfactant. Surfactant, synthesized by type II pneumocytes, reduces surface tension in the alveoli. Without sufficient surfactant, the alveoli tend to collapse, requiring greater effort to open, leading to rapid fatigue, atelectasis, and hypoxia. This ultimately results in epithelial and endothelial damage and the formation of hyaline membranes.
573
How is surfactant production regulated?
Surfactant production is stimulated by corticosteroids and suppressed by high levels of insulin, which counteract the effects of steroids.
574
Describe the morphology of the lungs in RDS.
The lungs are of normal size but heavy and relatively airless with a mottled purple color. Alveoli are poorly developed and collapsed. In infants who die within a few hours, only necrotic cellular debris is present in the bronchioles. In those who die after a few days, NRDS (Hyaline Membrane Disease) is characterized by collapsed alveoli, hyperaerated alveoli, vascular congestion, and hyaline membranes composed of fibrin and cellular debris.
575
What are the clinical features and complications of RDS?
The prognosis of RDS depends on the maturity and birth weight of the infant. Management includes delaying labor until lung maturity or inducing lung maturation. High concentrations of ventilator-administered oxygen, required for affected infants, can lead to complications such as retrolental fibroplasia (retinopathy of prematurity) and bronchopulmonary dysplasia.
576
What is Sudden Infant Death Syndrome (SIDS)?
SIDS refers to sudden unexpected infant deaths in infants younger than 12 months of age that occur suddenly and unexpectedly, without an obvious cause, even after a thorough investigation that includes complete autopsy, examination of the death scene, and review of clinical history. Infants usually die in their sleep.
577
Describe the pathogenesis of SIDS.
SIDS is multifactorial, involving:
A vulnerable infant with intrinsic developmental abnormalities in cardiorespiratory control, particularly in the brain stem (arcuate nucleus).
A critical period in the development of homeostatic control mechanisms, influenced by parental factors (young mother, smoking during pregnancy) and infant factors (brain stem abnormalities, prematurity).
Exogenous stressors such as prone sleep position, sleeping on soft surfaces, and hyperthermia.
578
What is the morphology of SIDS?
Morphological findings in SIDS include multiple petechiae on the thymus, visceral and parietal pleura, and epicardium. The lungs are congested and show vascular engorgement, with or without pulmonary edema. There is often hypoplasia of the arcuate nucleus in the brain stem.
579
What are some prevention strategies for SIDS?
Prevention strategies for SIDS include placing infants on their backs to sleep, using a firm sleep surface, keeping soft objects and loose bedding away from the infant’s sleep area, and avoiding overheating. Breastfeeding, regular prenatal care, and avoiding exposure to smoke and alcohol during pregnancy can also reduce the risk.
580
T98 + 99 What characterizes Idiopathic Pulmonary Fibrosis (IPF)?
IPF is a pulmonary disorder of unknown cause characterized by diffuse fibrosis of the lung interstitium. It is a chronic and progressive disease that often results in severe hypoxemia and death. Males are affected more than females, and about two-thirds of patients are over 60 years old.
581
What is the pathogenesis of IPF?
IPF is caused by repeated cycles of epithelial activation/injury by some unidentified agent. TGF-β1 is released from injured type I pneumocytes, inducing transformation of fibroblasts into myofibroblasts, leading to excessive and continuing deposition of collagen and ECM.
582
Describe the morphology of IPF.
Macro: The pleural surface has a cobblestone appearance due to the retraction of interlobular septa. Cut surface shows fibrosis, primarily affecting the subpleural regions and lower lung zones.
Micro: Characterized by patchy interstitial fibrosis, scattered fibroblastic foci, and architectural alteration due to chronic scarring or honeycomb change.
583
What are the clinical features of IPF?
Gradual onset of non-productive cough and progressive dyspnea. In later stages, patients may develop cyanosis, cor-pulmonale, and peripheral edema.
584
What characterizes Sarcoidosis?
Sarcoidosis is a multisystem disease of unknown cause characterized by non-caseating granulomas in many tissues and organs. Hilar nodes and lung involvement are the most common, leading to restrictive lung disease. It often affects young adults under 40 and has a higher prevalence in non-smokers
585
Describe the pathogenesis of Sarcoidosis.
Sarcoidosis is believed to result from a cell-mediated immune response to an unidentified antigen. This process is driven by CD4+ helper T cells, leading to intra-alveolar and interstitial accumulation of TH1 cells, increased TH1-derived cytokines, and subsequent macrophage activation. Genetic factors and environmental exposures also play a role.
586
What are the morphological features of Sarcoidosis?
Granulomas: Non-caseating granulomas composed of epithelioid cells and giant cells surrounded by T cells. Peripheral fibroblasts eventually replace granulomas with scar tissue.
Granulomas may contain Schauman bodies and Asteroid bodies. Lymph nodes are "nonmatted" and do not ulcerate. Commonly affects hilar and paratracheal lymph nodes, skin, eyes, salivary glands, liver, spleen, and bone.
587
What are the clinical features of Sarcoidosis?
Patients may present with non-specific symptoms such as fever, fatigue, and weight loss. Specific symptoms depend on the organ involved, such as cough and dyspnea in lung involvement, or visual disturbances with eye involvement.
588
What is Pneumoconiosis and what causes it?
Pneumoconiosis is a group of interstitial lung diseases caused by the inhalation of mineral dusts, organic or inorganic particles, leading to lung fibrosis. Common causes include exposure to coal dust, silica, and asbestos.
589
Describe the pathogenesis of Pneumoconiosis.
The severity of the disease depends on the size and reactivity of the inhaled particles. Small particles reach the distal airways and are phagocytosed by alveolar macrophages, leading to the release of inflammatory and fibrogenic mediators such as TGF-β, which induces fibroblast proliferation and fibrosis.
590
What are the common types of Pneumoconiosis?
1. Coal Worker’s Pneumoconiosis (CWP): Characterized by coal macules and nodules, which can progress to complicated CWP with massive fibrosis.
2. Silicosis: Caused by inhalation of silica particles, leading to nodular fibrosis.
3. Asbestosis: Caused by asbestos exposure, leading to diffuse interstitial fibrosis and pleural plaques.
4. Berylliosis: Caused by inhalation of beryllium, leading to hypersensitivity granulomatous disease and increased risk for lung cancer.
591
What are the clinical features of Pneumoconiosis?
Patients present with progressive dyspnea, cough, and symptoms related to pulmonary fibrosis. Advanced cases may lead to pulmonary hypertension and cor pulmonale. Specific features depend on the type of pneumoconiosis, such as pleural plaques in asbestosis or nodular fibrosis in silicosis.
592
What is Coal Worker’s Pneumoconiosis (CWP)?
CWP is caused by the inhalation of coal dust, leading to the accumulation of coal macules and nodules in the lungs. It can progress to complicated CWP or progressive massive fibrosis (PMF), which results in extensive lung fibrosis and compromised lung function.
593
Describe the morphology of Coal Worker’s Pneumoconiosis.
Anthracosis: Inhaled carbon pigment is engulfed by macrophages, which accumulate in the connective tissue along lymphatics and lymph nodes.
Simple CWP: Characterized by coal macules (dust-laden macrophages) and nodules (macules with small amounts of collagen).
Complicated CWP/PMF: Extensive black scars in the lung tissue due to massive fibrosis.
594
What is Silicosis and what causes it?
Silicosis is caused by the inhalation of silica particles, commonly in occupational settings such as sandblasting and mining. It leads to the formation of nodular fibrosis in the lungs.
595
Describe the pathogenesis of Silicosis.
Inhaled silica particles interact with epithelial cells and macrophages. Ingested silica causes macrophage activation and release of inflammatory mediators, leading to fibrosis. Silica also impairs phagolysosome formation, increasing susceptibility to tuberculosis.
596
What are the morphological features of Silicosis?
Early Stage: Tiny, discrete, pale-to-blackened nodules in the upper lung zones.
Micro: Concentric hyalinized collagen fibers surrounding an amorphous center.
Progression: Coalescence of nodules into hard, collagenous scars, leading to progressive massive fibrosis (PMF). Honeycomb pattern may develop.
597
What is Asbestosis and what causes it?
Asbestosis is a form of interstitial pulmonary fibrosis caused by the inhalation of asbestos fibers, commonly in occupational settings such as construction and shipyard work. It can also lead to pleural plaques, lung carcinoma, mesotheliomas, and pleural effusions.
598
Describe the pathogenesis of Asbestosis.
Inhaled asbestos fibers are phagocytosed by macrophages, triggering the release of fibrogenic and inflammatory mediators. This leads to interstitial fibrosis, initially around respiratory bronchioles and alveolar ducts, and later extending to involve the entire lung, often with subpleural and lower lobe predilection.
599
What are the morphological features of Asbestosis?
- Diffuse Interstitial Fibrosis: Begins in lower lobes and subpleurally, progressing to middle and upper lobes.
- Asbestos Bodies: Golden-brown, beaded rods consisting of asbestos fibers coated with iron-containing proteinaceous material.
- Pleural Plaques: Collagenous plaques on the parietal pleura, not containing asbestos bodies.
- Honeycomb Lung: Advanced fibrosis with cystically dilated airspaces enclosed by fibrous walls.
600
What is Berylliosis and what causes it?
Berylliosis, or chronic beryllium disease (CBD), is a hypersensitivity granulomatous disease caused by inhalation of beryllium and its compounds, commonly affecting workers in the aerospace industry or beryllium mining.
601
Describe the pathogenesis of Berylliosis.
Inhalation of beryllium leads to a delayed-type hypersensitivity reaction, where beryllium acts as a hapten antigen, stimulating local proliferation and accumulation of beryllium-specific T cells. This results in non-caseating granulomas mainly in the lungs and hilar lymph nodes, and potentially other organs.
602
What are the clinical features of Berylliosis?
Patients experience cough, shortness of breath, chest pain, joint aches, weight loss, and fever. Symptoms can develop weeks to years after exposure. Granulomas may also form in other organs, including the liver. The disease can increase the risk of lung cancer.
603
T100 What is the primary origin of pulmonary thromboembolism and what is a less common alternative?
The vast majority of pulmonary thromboembolisms originate from thrombi in the deep veins of the lower limbs (above the knee level). A less common alternative is a paradoxical embolism from the systemic circulation.
604
What are the risk factors for venous thrombosis leading to pulmonary thromboembolism?
Prolonged bed rest
Orthopedic surgery of the knee and hip, or injury to the endothelium
Primary disorders of hypercoagulability
605
Why are most pulmonary thromboembolism events clinically silent?
Approximately 80% of events are clinically silent because the lungs have a dual blood supply from the pulmonary arteries and the bronchial arteries. This dual supply helps maintain adequate perfusion even if one pathway is blocked. Additionally, many emboli are small and self-resolving through processes like organization or fibrinolysis, thus having minimal impact on blood supply.
606
What are the consequences of large pulmonary emboli?
Large emboli can lodge in the main pulmonary artery, its major branches, or at its bifurcation (saddle embolus). This can lead to increased pulmonary artery pressure, diminished cardiac output, right-sided heart failure (cor pulmonale), and potentially sudden death due to an acute increase in pulmonary pressure and sudden collapse of circulation.
607
What happens when small emboli occur in a patient with compromised cardiovascular status?
In patients with compromised cardiovascular status, such as those with congestive left-sided heart failure, small emboli can result in pulmonary infarction because these patients cannot maintain adequate perfusion through the bronchial arteries.
608
What mechanisms lead to hypoxemia in pulmonary thromboembolism?
Hypoxemia in pulmonary thromboembolism occurs due to several mechanisms:
Perfusion of lung areas that have become atelectatic. Ischemia reduces surfactant production, leading to alveolar collapse.
Blood flow is redirected to areas with better oxygen perfusion, but decreased cardiac output widens the arterial-venous oxygen saturation difference.
609
What is embolization?
Embolization is the process by which intravascular solid, liquid, or gaseous material is carried by the bloodstream away from its site of origin, causing obstruction of a blood vessel. This can lead to clinical symptoms depending on the organ affected by the obstruction.
610
What is a hemorrhagic pulmonary infarction?
A hemorrhagic infarction of the lung is an area of ischemic necrosis produced by blood vessel obstruction against a background of passive congestion from the lung's dual blood supply.
611
Describe the morphology and histology of a pulmonary infarction.
Infarction typically presents as a wedge-shaped area with the base toward the pleura and the blocked vessel found at the apex.
Fresh infarcts display coagulative necrosis and hemorrhage.
Lysis of red blood cells causes the infarct to pale and produce hemosiderin, resulting in a red-brown color.
Scar tissue eventually forms, leading to fibrous replacement and a grey-white appearance.
612
Histology of a pulmonary infarction
Alveolar walls, vascular walls, and bronchioles in the infarcted area are necrotic and appear eosinophilic (pink), homogenous, and lack nuclei but retain their shapes, indicative of coagulative necrosis.
Alveolar lumens in the infarcted area are filled with red blood cells, indicating a hemorrhagic infarct (red).
613
What are diffuse alveolar hemorrhage syndromes, and what is the clinical triad they present with?
Diffuse alveolar hemorrhage syndromes are immune-mediated diseases presenting with a triad of hemoptysis (coughing up blood), anemia, and diffuse pulmonary infiltration.
614
What is Goodpasture syndrome, and what causes it?
Goodpasture syndrome is characterized by a proliferative, rapidly progressive glomerulonephritis and hemorrhagic interstitial pneumonitis, both caused by antibodies against part of collagen IV.
615
Describe the morphology and histological features of Goodpasture syndrome in the lungs.
Morphology:
Diffuse alveolar hemorrhage.
Histology:
Focal necrosis of alveolar walls associated with intra-alveolar hemorrhage.
Fibrous thickening of septa and hypertrophy of septal lining cells.
Presence of IgG antibodies showing a linear pattern of deposition in immunofluorescence.
616
T101 + 102 What is pneumonia and what causes its development?
Pneumonia is broadly defined as any infection in the lung. The development of such an infection is due to the impairment of normal defense mechanisms or lowered host resistance. Normal defense mechanisms include nasal clearance (sneezing, blowing, swallowing), tracheobronchial clearance (mucociliary action), and alveolar clearance (alveolar macrophages). Impairment can be due to primary or acquired immunosuppression, suppression of the cough reflex (drugs, virus, coma, anesthesia), injury to the mucociliary apparatus (smoking, virus, Kartagener's syndrome), injury to macrophages (tobacco, alcohol, anoxia), pulmonary congestion/edema, or accumulation of secretions (cystic fibrosis). Note: viral pneumonia predisposes individuals to bacterial pneumonia.
617
What are the two patterns of acute bacterial typical pneumonia seen on chest x-ray?
Bronchopneumonia: Characterized by patchy distribution of inflammation around bronchioles, often multifocal and bilateral, affecting more than one lobe. It results from an initial infection of bronchioles that extends into the alveoli.
Lobar pneumonia: Involves full segments homogeneously filled with exudates, seen as segmental or lobar consolidation. The main causative agent is Streptococcus pneumoniae. Classic lobar pneumonia involves the entire lobe and progresses through four gross phases: congestion, red hepatization, gray hepatization, and resolution.
618
What is bronchopneumonia, and which bacteria are commonly associated with it?
Bronchopneumonia is an acute inflammation of the walls of the bronchioles associated with specific bacteria such as Staphylococcus aureus, Klebsiella, E. coli, and Pseudomonas.
619
Describe the morphology of bronchopneumonia.
Macroscopic: Affects one or more lobes, frequently bilateral and basal. Identifiable by multiple foci of condensation (1-3 cm diameter), white-yellowish, imprecisely circumscribed, centered by bronchioles, separated by normal lung parenchyma. Pleural involvement is less common than in lobar pneumonia. In children, it can result in large condensation areas (pseudo lobar pneumonia).
Microscopic: Foci of inflammatory condensation centered by a bronchiole with acute bronchiolitis (suppurative exudate rich in neutrophils in the lumen, foci of ulceration of the epithelium, and parietal inflammation). Alveolar lumens surrounding the bronchi are filled with neutrophils (leukocytic alveolitis). Capillaries in the alveolar walls show congestion. Inflammatory foci are separated by normal, aerated parenchyma.
620
What are the complications associated with bronchopneumonia?
Tissue destruction and necrosis leading to abscess formation.
Accumulation of suppurative material in the pleural cavity, resulting in empyema.
Organization of the intra-alveolar exudates that may convert areas of the lung into solid fibrous tissue.
Bacterial dissemination can lead to conditions such as meningitis, arthritis, or infective endocarditis.
621
T101 + 102
622
What is meant by "primary atypical pneumonia," and how does it differ from typical pneumonia?
"Primary atypical pneumonia" is called primary because it develops independently of other diseases. It is considered atypical due to its presentation, which includes only moderate amounts of sputum, absence of physical findings of consolidation, moderate elevation in WBC count, and lack of alveolar exudates.
623
What is the most common causative agent of community-acquired atypical pneumonia?
The most common causative agent of community-acquired atypical pneumonia is Mycoplasma pneumoniae.
624
List some of the key features of atypical pneumonia compared to typical pneumonia.
Key features of atypical pneumonia compared to typical pneumonia include:
Moderate amounts of sputum production
Absence of physical findings of consolidation
Moderate elevation in WBC count
Lack of alveolar exudates
625
T103 What are the four major histologic types of lung carcinomas?
The four major histologic types of lung carcinomas are:
Squamous cell carcinoma
Adenocarcinoma
Large cell carcinoma
Small cell carcinoma
626
How are lung carcinomas therapeutically divided and treated?
Lung carcinomas are divided into small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). SCLC metastasizes by the time of diagnosis, making surgery ineffective; it is better treated by chemotherapy.
NSCLC, on the other hand, is better treated by surgery. Now, therapies targeting specific mutated gene products are available, especially in adenocarcinomas, making further sub-classification into histologic and molecular subtypes necessary.
627
Describe the pathogenesis of lung carcinomas.
Carcinomas of the lungs arise due to the transformation of normal bronchial epithelium or pneumocytes into neoplastic cells. Major contributing factors include:
Cigarette Smoking: 85% of lung cancers are related to smoking, especially due to polycyclic aromatic hydrocarbons and arsenic.
Environmental Insults: Exposure to asbestos (linked to both lung cancer and mesothelioma) and radon (a gas from uranium decay in soil) also contribute.
Genetic Changes: Mutation accumulation in a predictable order, with early inactivation of tumor suppressor genes (e.g., short arm of chromosome 3) and later mutations in genes like p53.
Histologic Subtypes and Smoking: Squamous and small-cell carcinomas show the strongest association with tobacco exposure.
628
What is the significance of the genetic mutation order in the pathogenesis of lung cancer?
In the pathogenesis of lung cancer, especially related to smoking, genetic mutations occur in a predictable order:
Early Stage: Inactivation of tumor suppressor genes (e.g., short arm of chromosome 3) even in "healthy" smoker's respiratory epithelium.
Later Stage: Mutations in p53 and other genes, contributing to progression from hyperplasia and squamous metaplasia to squamous dysplasia, carcinoma in situ, and ultimately invasive cancer.
629
Which histologic subtypes of lung cancer have the strongest association with tobacco exposure?
Squamous cell carcinoma and small cell carcinoma show the strongest association with tobacco exposure.
630
Describe the initial appearance and progression of lung carcinomas in terms of morphology.
Carcinomas begin as firm, gray-white, small mucosal lesions. They may form intraluminal masses, invade the bronchial mucosa, or form large masses pushed into adjacent lung parenchyma. Some large masses might undergo cavitation due to central necrosis or develop focal areas of hemorrhage. Eventually, these tumors may invade the pleural cavity and chest wall.
631
What are the typical clinical features of lung carcinomas?
Lung carcinomas are often silent lesions that spread extensively before symptoms appear. When symptoms do manifest, they can include cough, sputum production, weight loss, dyspnea, bronchiectasis, or pneumonia. NSCLCs have a better prognosis than SCLCs and can potentially be cured by lobectomy or pneumonectomy if detected before metastasis. SCLCs are very sensitive to chemotherapy.
632
List the paraneoplastic syndromes associated with lung carcinomas and the most common types they are associated with.
Paraneoplastic syndromes associated with lung carcinomas include:
Hypercalcemia due to secretion of PTH-related peptide (most often encountered in squamous cell carcinoma).
Cushing syndrome from increased production of ACTH.
Syndrome of inappropriate secretion of ADH (SIADH).
Neuromuscular syndromes.
Clubbing of the fingers.
Thrombophlebitis, non-bacterial endocarditis, and disseminated intravascular coagulation (DIC).
Squamous cell carcinoma is often associated with hypercalcemia.
Adenocarcinoma is often associated with hematologic syndromes.
Small cell carcinoma is often associated with the remaining syndromes.
633
Describe the characteristics and treatment of small cell carcinoma (SCLC).
Small cell carcinoma has usually metastasized by the time of diagnosis, making it incurable by surgery. It is treated by chemotherapy, with or without radiation.
This carcinoma is highly associated with male smokers and consists of poorly differentiated, relatively small cells. Originating from neuroendocrine cells (APUD cells) in the bronchus (Feyrter cells), it expresses various neuroendocrine markers and can lead to ectopic hormone production, resulting in paraneoplastic syndromes and Cushing's syndrome.
The tumor appears as centrally located pale-gray masses, with extensive necrosis and early involvement of hilar lymph nodes. It is associated with chromosome 3 deletions, RB gene mutations, and p53 mutations.
634
What is the origin of small cell carcinoma and what are its associated genetic mutations?
Small cell carcinoma is thought to originate from neuroendocrine cells (APUD cells) in the bronchus called Feyrter cells. It is associated with several genetic mutations, including chromosome 3 deletions, RB gene mutations, and p53 mutations.
635
What are the primary features and common sites of squamous cell carcinoma in the lungs?
Squamous cell carcinoma is the most common lung tumor in male smokers and is generally more common in men than women. It tends to arise centrally in major bronchi and spreads to local hilar lymph nodes.
Larger lesions may undergo necrosis, leading to cavitation. This carcinoma is usually preceded by squamous metaplasia or dysplasia in the bronchial epithelium, which progresses to carcinoma in situ, then to a well-defined tumor mass that obstructs the bronchus lumen, causing distal atelectasis and infection.
636
What are the histological features and associated genetic mutations of squamous cell carcinoma?
The cells of squamous cell carcinoma range from well-differentiated squamous cell neoplasms showing keratin pearls and/or intercellular bridges to poorly differentiated neoplasms. This carcinoma is associated mainly with chromosome 3 short arm deletion and p16 mutations. Additionally, it may produce PTH-related peptide, leading to hypercalcemia in some patients.
637
What is the most common type of lung tumor in non-smokers and females, and what are its characteristics?
Adenocarcinoma is the most common lung tumor in non-smokers and females. Tumor cells form glands that produce mucin, usually forming smaller masses compared to other lung cancers. It grows slowly but metastasizes earlier than other tumors. Adenocarcinomas are typically located more peripherally in the lungs, increasing the risk of pleural involvement.
638
Describe the precursor lesions and progression of adenocarcinoma.
The precursor of peripheral adenocarcinomas is thought to be atypical adenomatous hyperplasia (AAH), which can progress to:
1. Adenocarcinoma in situ (formerly known as bronchioalveolar carcinoma): Less than 3 cm in diameter, grows along preexisting structures as a monolayer of cuboidal tumor cells without invading the stroma, maintaining alveolar architecture (lepidic growth).
2. Minimal invasive adenocarcinoma: Less than 3 cm but with an invasive component.
3. Invasive adenocarcinoma: Invasion depth more than 5 mm.
639
What are the histological patterns seen in adenocarcinoma?
Adenocarcinoma usually presents mixed histological patterns and is classified by the predominant one:
Acinar pattern: Gland formation.
Papillary pattern: Fibromuscular cores lined by glandular tumor cells replacing normal alveolar lining (micropapillary has no fibromuscular core but similar papillary pattern).
Mucinous pattern: Grows along alveolar septa, not invasive (in situ).
Solid type: Tumor cells contain mucin, forming solid masses of cells, often requiring special stains for recognition.
640
What genetic mutations and immunohistochemical markers are associated with adenocarcinoma?
Adenocarcinoma is mainly associated with chromosome 3 short arm deletion and p16 mutations. The immunohistochemical profile can help differentiate it from other types of NSCLC. About 70% of adenocarcinomas are positive for thyroid transcription factor-1 (TTF-1).
641
What is adenocarcinoma in situ (AIS), formerly known as bronchioloalveolar carcinoma?
Adenocarcinoma in situ (AIS), formerly called bronchioloalveolar carcinoma, often involves peripheral parts of the lung, typically presenting as a single nodule.
642
What is the maximum diameter of adenocarcinoma in situ (AIS)?
The maximum diameter of adenocarcinoma in situ (AIS) is 3 cm or less.
643
How does adenocarcinoma in situ (AIS) grow?
AIS grows along preexisting alveolar structures without invading them, and preserves the alveolar architecture
644
What types of cells can be found in adenocarcinoma in situ (AIS)?
The tumor cells in AIS can be nonmucinous, mucinous, or mixed, and they grow in a monolayer along the alveolar septa.
645
Does adenocarcinoma in situ (AIS) show destruction of alveolar architecture or stromal invasion?
No, AIS does not demonstrate destruction of alveolar architecture or stromal invasion with desmoplasia (no growth of fibrous tissue).
646
How is large cell carcinoma classified in terms of lung cancer types?
Large cell carcinoma is considered a non-small cell lung carcinoma (NSCLC).
647
How does large cell carcinoma typically respond to chemotherapy?
Large cell carcinoma responds poorly to chemotherapy and is thus treated by surgery.
648
What is large cell carcinoma commonly associated with?
Large cell carcinoma is commonly associated with smoking
649
What characterizes the tumor cells in large cell carcinoma
The tumor cells in large cell carcinoma are undifferentiated epithelial tumors that lack the cytologic features of small cell carcinoma, show no glandular differentiation or mucin, and have no keratin pearls or intercellular bridges.
650
Where can large cell carcinoma be located in the lungs?
Large cell carcinoma can be central or peripheral in the lungs.
651
What type of cells do bronchial carcinoid tumors originate from?
Bronchial carcinoid tumors originate from the diffuse neuroendocrine system of the lung (Korchinski cells).
652
What is the characteristic histological feature of typical carcinoid tumors?
Typical carcinoid tumors are composed of nests of uniform cells with regular round nuclei, "salt and pepper" chromatin, and central nucleoli. They have less than 5 mitotic figures per high-power field (HPF) and no necrosis.
653
How are atypical carcinoid tumors different from typical carcinoid tumors?
Atypical carcinoid tumors have more than 5 mitotic figures per HPF (40x objective) and may show focal necrosis. They display a higher mitotic rate than typical carcinoids but less than small or large cell carcinomas.
654
Where do most bronchial carcinoid tumors originate?
Most bronchial carcinoid tumors originate in the main bronchi.
655
What are the two growth patterns of bronchial carcinoid tumors?
Bronchial carcinoid tumors can grow in two patterns:
Expanding growth as an obstructing polypoid, spherical, intraluminal mass.
Invasing growth as a mucosal plaque that penetrates the bronchial wall to spread into the peribronchial tissue.
656
What are the clinical symptoms of bronchial carcinoid tumors?
Clinical symptoms include cough and recurrent infections related to intramural growth. Rarely, carcinoid syndrome may occur, characterized by attacks of diarrhea, flushing, and vomiting.
657
Are distant metastases common in bronchial carcinoid tumors?
No, distant metastases are rare in both typical and atypical bronchial carcinoid tumors.
658
Are bronchial carcinoid tumors typically curable?
Yes, bronchial carcinoid tumors are often resectable and curable.
659
T104 What are the primary disorders of the pleura?
Primary disorders of the pleura include primary intrapleural bacterial infections and primary neoplasm of the pleura known as malignant mesothelioma.
660
What is pleural effusion and how can it be classified?
Pleural effusion is the presence of fluid in the pleural space. It can be classified as transudate (hydrothorax) or exudate (containing proteins and inflammatory cells).
661
What is the most common cause of hydrothorax?
The most common cause of hydrothorax is congestive heart failure (CHF).
662
What are the causes of pleural exudate formation?
The causes of pleural exudate formation are microbial invasion (empyema), cancer (lung carcinoma, metastasis, mesothelioma), pulmonary infarction, and viral pleuritis.
663
What are the complications of fibrinous, hemorrhagic, and suppurative exudates in pleural effusion?
Fibrinous, hemorrhagic, and suppurative exudates may lead to fibrous organization, yielding adhesions or fibrous pleural thickening, and sometimes minimal to massive calcifications.
664
What is pneumothorax and how is it classified?
Pneumothorax refers to air or other gas in the pleural sac. It is classified as primary (simple/spontaneous) without any pulmonary disease and secondary as a result of thoracic or lung disorder.
665
What are the complications of pneumothorax?
Complications of pneumothorax include tension pneumothorax, compromised pulmonary circulation, serous fluid collection leading to hydro pneumothorax, and prolonged collapse leading to infections and empyema (pyopneumothorax).
666
What is hemothorax and its common cause?
Hemothorax is the collection of whole blood in the pleural cavity. It is commonly caused by ruptured intrathoracic aortic aneurysm, which is almost always fatal.
667
How does hemothorax differ from bloody pleural effusion?
Hemothorax involves the collection of whole blood with clots in the pleural cavity, whereas bloody pleural effusion has no blood clots.
668
What is chylothorax and its common implication?
Chylothorax is the pleural collection of lymphatic fluid containing microglobules of lipids. Its presence usually implies an obstruction of major lymph ducts, often by intrathoracic cancer.
669
What is malignant mesothelioma?
Malignant mesothelioma is a rare cancer of mesothelial cells, usually arising in the pleura (either visceral or parietal), but less commonly occurs in the peritoneum and pericardium.
670
What is a significant risk factor for malignant mesothelioma?
Approximately 50% of malignant mesothelioma cases are related to exposure to asbestos in the air.
671
Describe the morphology of malignant mesothelioma.
Malignant mesothelioma is preceded by extensive pleural fibrosis. The tumors begin in a localized area and spread widely over time, enveloping the affected lung in a yellow-white, firm, gelatinous layer of tumor.
672
What are the three patterns of mesothelioma?
The three patterns of mesothelioma are:
Epithelial – cuboidal cells line tubular and microcystic spaces with small papillary buds projecting into them, which is the most common.
Sarcomatous – spindle-shaped cells grow in non-distinctive sheets.
Biphasic – both epithelial and sarcomatous patterns appear.
673
What are the clinical features of malignant mesothelioma?
Malignant mesothelioma presents with recurrent pleural effusions, dyspnea, and chest pain.
674
T105 What are the characteristics and common pathogens of the "common cold"?
The "common cold" is characterized by nasal congestion accompanied by watery discharge, sneezing, sore throat, and a slight increase in temperature. The common pathogens that elicit the common cold are rhinoviruses. Most infections are self-limited.
675
What are the symptoms and common cause of pharyngitis?
Acute pharyngitis is manifested as a sore throat. Mild pharyngitis frequently accompanies a cold and is the most common form of pharyngitis.
676
What causes tonsillitis and what are its potential complications?
Tonsillitis occurs with Streptococcus pyogenes and adenovirus infections. In streptococcal tonsillitis, peritonsillar abscesses may develop.
677
What are the common cause and symptoms of acute bacterial epiglottitis
Acute bacterial epiglottitis occurs in young children due to infection of the epiglottis by Haemophilus influenzae. Common findings include pain and airway obstruction.
678
What are the causes of acute laryngitis and its less common forms?
Acute laryngitis results from inhalation of irritants or by allergic reactions. It may also be caused by the agents that produce the common cold and usually involves the pharynx and nasal passages as well as the larynx. Less common forms include tuberculous laryngitis and diphtheritic laryngitis.
679
What are the characteristics and hazards of diphtheritic laryngitis?
Diphtheritic laryngitis is caused by Corynebacterium diphtheriae, which implants on the mucosa of the upper airways and elaborates a powerful exotoxin. This causes necrosis of the mucosal epithelium, accompanied by a dense fibrinopurulent exudate, creating the pseudomembrane of diphtheria. Major hazards include obstruction of major airways and absorption of bacterial exotoxins, which can produce myocarditis, peripheral neuropathy, or other tissue injury.
680
What is nasopharyngeal carcinoma and its relationship to EBV?
Nasopharyngeal carcinoma is a rare neoplasm closely related to Epstein-Barr Virus (EBV). EBV infects the host by first replicating in the nasopharyngeal epithelium and then infecting nearby tonsillar B lymphocytes.
681
What are the three histological variants of nasopharyngeal carcinoma?
The three histological variants of nasopharyngeal carcinoma are:
Keratinizing squamous cell carcinoma.
Non-keratinizing squamous cell carcinoma.
Undifferentiated carcinoma (most common, most linked to EBV).
682
Describe the characteristics of undifferentiated carcinoma in nasopharyngeal carcinoma.
Undifferentiated carcinoma, the most common type linked to EBV, is characterized by large epithelial cells with indistinct borders ("syncytial" growth) and eosinophilic nucleoli.
683
What is lymphoepithelioma in the context of nasopharyngeal carcinoma?
Lymphoepithelioma refers to nasopharyngeal carcinoma with a massive influx of mature lymphocytes into the tumor, typically seen in undifferentiated carcinoma linked to EBV.
684
How does nasopharyngeal carcinoma typically spread?
Nasopharyngeal carcinomas typically invade locally, spread to cervical lymph nodes, and then metastasize to distant areas.
685
What are the characteristics of vocal cord nodules?
Vocal cord nodules, also known as "polyps," are smooth and hemispheric protrusions located on the true vocal cords. They are composed of fibrous tissue covered by stratified squamous mucosa and occur mainly in heavy smokers or singers due to chronic irritation or abuse.
686
Describe laryngeal papilloma
Laryngeal papilloma, or squamous papilloma of the larynx, is a benign neoplasm usually found on the true vocal cords. It forms a soft, raspberry-like lump with multiple finger-like projections supported by central fibrovascular cores and covered by stratified squamous epithelium. It is caused by HPV6 and HPV11, does not become malignant, and often spontaneously regresses at puberty. It appears as a single lesion in adults and multiple lesions in children.
687
What are the common causes and characteristics of carcinoma of the larynx?
Carcinoma of the larynx commonly occurs after the age of 40, more frequently in men, and is influenced by environmental factors such as smoking, alcohol, and asbestos exposure.
Most laryngeal carcinomas (95%) are typical squamous cell carcinomas, usually developing directly on the vocal cords but can also arise above (supraglottic) or below (subglottic) the cords. They begin as in situ lesions that later appear as gray, wrinkled plaques on the mucosal surface, causing ulceration and fungation.
688
How do glottis and supraglottic tumors differ in their likelihood to metastasize?
Glottis tumors, which are usually keratinizing, well-differentiated squamous cell carcinomas, are less likely to metastasize due to low lymphatic supply. In contrast, supraglottic tumors are more likely to metastasize to cervical lymph nodes.
689
What is the clinical manifestation of laryngeal carcinoma?
Laryngeal carcinoma clinically manifests as hoarseness. This symptom is often an early indicator of the disease, prompting further investigation and diagnosis.
