Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
291 Cards in this Set
- Front
- Back
|
What are the 4 signs of reversible cell injury?
|
1. Swelling of cell organelles and entire cell 2. dissociation of ribosomes from endoplasmic reticulum 3. decreased energy production by mitochondria 4. increased glycolysis -> decreased pH -> nuclear chromatin clumping
|
|
|
What are the 4 signs of irreversible cell enjury
|
1. dense bodies within mitochondria 2. release of cellular enzymes 3. nuclear degeneration 4. cell death
|
|
|
Hereditary thrombophilia can be caused by a deficiency in what?
|
Antithrombotic proteins: antithrombin III, protein C, and protein S
|
|
|
What is Leber Hereditary Optic Neuropathy?
|
Bilateral loss of vision (between ages 15-35), transmitted through mitochondrial DNA (from mother)
|
|
|
What is Tay Sach's disease?
|
Lysosomal storage disease (autosomal recessive, high prevalence for Ashkenazi Jews), deficiency of hexoaminidase A, associated with developmental delays/neurologic deficits, "cherry red macula"
|
|
|
What disease is characterized by multiple tandem repeats of CGG in DNA?
|
Fragile X Syndrome
|
|
|
hypertrophy
|
increase in size of cells
|
|
|
hyperplasia
|
increase in number of cells
|
|
|
aplasia
|
failure of cell production
|
|
|
agensis
|
absence of an organ due to failure of production
|
|
|
hypoplasia
|
decrease in cell production that is less extreme than that found in aplasia
|
|
|
atropy
|
decreasein mass of pre-existing cells
|
|
|
metaplasia
|
replacement of one differentiated tissue by another
|
|
|
associated with squamous metaplasia
|
chronic irritation (tobacco use), vitamin A deficiency [this is usually reversible]
|
|
|
ischemia
|
obstruction of arterial blood flow
|
|
|
anemia
|
reduction in number of oxygen-carrying red blood cells
|
|
|
early stage of hypoxic cell injury
|
affects mitochondria resulting in decreased oxidative phosphylation and ATP synthesis
|
|
|
consequences of decreased ATP availability (in hypoxic cell injury)
|
1. failure of the cell membrane pump 2. disaggregation of ribosomes and failure of protein synthesis 3. stimulation of phosphofructokinase activity
|
|
|
What does failure of the cell membrane pump lead to?
|
failure of cell membrane pump (ouabain-sensitive sodium potassium pump) (leads to increased intracellular sodium and water, decreased intracellular potassium), causes cellular swelling, endoplasmic reticulum swelling, and mitochondrial swelling
|
|
|
late stage of hypoxic cell injury
|
membrane damage with two reversible morphologic signs: myelin figures and cell blebs
|
|
|
What happens with hypoxic cell death
|
The point of no return is marked by irreversible damage to cell membranes, leading to massive calcium influx, extensive calcification of the mitochondria, and cell death (also intracellular enzymes and various other proteins are released)
|
|
|
Describe how vulnerable various cells are to hypoxic injury
|
3-5 minutes for neurons, 1-2 hours for myocardial cells and hepatocytes, many hours for skeletal muscle cells
|
|
|
How are free radicals generated?
|
1. normal metabolism 2. oxygen toxicity 3. ionizing radiation 4. ultraviolet light 5. drugs and chemicals 6. reperfusion after ischemic injury
|
|
|
How are free radicals degraded?
|
1. intracellular enzymes (glutathione peroxidase, catalase, superoxide dismutase) 2. exogenous and endogenous antioxidants (vit A, C, E, cysteine, glutathione, selenium, ceruloplasmin, or transferrin) 3. spontaneous decay
|
|
|
Types of necrosis
|
1. coagulative necrosis 2. liquefactive necrosis 3. caseous necrosis 4. gangenous necrosis 5. fibrinoid necrosis 6. fat necrosis
|
|
|
pyknosis
|
chromatin clumping and shrinking with increased basophilia
|
|
|
karyorrhexis
|
fragmentation of chromatin
|
|
|
karyolysis
|
fading of chromatin material
|
|
|
gene regulators of apoptosis
|
bcl-2 (gene product inhibits apoptosis), bax (facilitates apoptosis), p53 (facilitates apoptosis by decreasing transcription of bcl-2 and increasing transcription of bax)
|
|
|
What endogenous pigments can accumulate?
|
melanin, bilirubin, hemosiderin, lipofuscin
|
|
|
How does melanin accumulate?
|
Formed from tyrosine from tyrosinase, synthasized in melanosomes, transferred to keratinocytes. Associated with suntanning and various diseases. Decreased pigmentation observed in albinism and vitiligo
|
|
|
How does bilirubin accumulate?
|
It is a catabolic product of hemoglobin (and myoglobin), accumulates from hemolytic jaundice (destruction of red cells) and hepatocellular jaundice (parenchymal liver damage), and obstructive jaundice (intra or extrahepatic obstruction of the biliary tract)
|
|
|
How does hemosiderin accumulate?
|
It is an iron-containing pigment that consists of aggregates of ferritin. Stained with Prussian blue dye. Hemosiderosis is accumulation of hemosiderin within tissue macrophages. Hemochromatosis is extensive accumulation occurs from Heriditary hemochromatosis and Secondary hemochromatosis
|
|
|
What is hereditary hemochromatosis?
|
Usually caused by a mutation of the Hfe gene on chromosome 6. Results in micronodular cirrhosis, diabetes mellitus, and skin pigmentation (referred to as "bronze diabetes"). Laboratory abnormalities: increased serum iron and decreased total iron-binding capacity (TIBC)
|
|
|
What is secondary hemochromatosis?
|
Most often caused by multiple blood transfusions adminstered to subjects \with hereditary hemolytic anemias.
|
|
|
How does lipofuscin accumulate?
|
End product of membrane lipid peroxidation (called "wear-and-tear" pigment), is a yellowish, fat-soluble pigment, accumulates in elderly patients
|
|
|
What are the two types of pathologic calcifications?
|
Metastatic calcification (occurs from hypercalcemia) and dystrophic calcification (occurs in previously damaged tissue, normal serum calcium levels)
|
|
|
What are disorders characterized by abnormalities of protein folding?
|
They involve failure of protein structural stabilization or degradation proteins known as chaperones
|
|
|
Ubiquitin
|
important chaperone which marks abnormal proteins for degradation
|
|
|
Abnormal protein aggregation
|
characteristic of amyloidosis (occurs in a number of neurodegenerative diseases: Alzheimer's, Huntington's, and Parkinson's)
|
|
|
Abnormal protein transport and secretion
|
characteristic of cystic fibrosis and alpha1-antitrypsin deficiency
|
|
|
5 cardinal signs of inflammation
|
rubor, dolor, calor, tumor, functio laesa
|
|
|
Dolor is mediated by?
|
Increased pressure exerted by the accumulation of interstitial fluid and mediators such as bradykinin
|
|
|
Bradykinin mediates?
|
increased vascular permeability and pain
|
|
|
C3a and C5a cause
|
degranulation of mast cells
|
|
|
What assists opsonization
|
IgG and C3b
|
|
|
Histamine mediates
|
endothelial cell contraction (increasing vascular permeability)
|
|
|
labile cells
|
cells that actively divide throughout life to replace lost cells (cells of epidermis and GI)
|
|
|
stable cells
|
cells that undergo few divisions but are capable of division when activited (includes hepatocytes, smooth muscle, connective tissue, etc.)
|
|
|
permanent cells
|
cells that are inapable of division and regeneration (neurons and myocardial cells), replaced by scar tissue after irreversible injury and cell loss
|
|
|
Granulomas
|
nodular collections of specialized macrophages referred to as epitheliod cells
|
|
|
ecchymocis
|
diffuse hemorrhage (usually in skin and subcutaneous tissue)
|
|
|
hyperemia
|
localized increase in the volume of blood in capillaries and small vessels
|
|
|
active hyperemia
|
localized ateriolar dilation (ex. Blushing, inflammation)
|
|
|
chronic passive congestion of the lung
|
most often caused by left heart failure or mitral stenosis,congestion and distention of alveolar capillaries lelad to capillary rupture and passage of red cells into the alveoli, phagocytosis and degration of red blood cells result in intra-alveolar hemosiderin-laden macrophages called heart-failure cells, long standing congestion, fibrosis of interstitium and hemosiderin deposition result in brown induration of the lung
|
|
|
chronic passive congestion of the liver and lower extremeties
|
associated with right heart failure (nutmeg liver may appear)
|
|
|
infarction
|
necrosis resulting from ischemia
|
|
|
anemic infarcts
|
white or pale infarcts usually caused by arterial occlusions in heart, spleen, and kidney
|
|
|
hemorrhagic infarcts
|
red infarcts, usually in the lung and GI
|
|
|
thrombosis
|
intravascular coagulation of blood
|
|
|
platelets participate in endothelial repair through:
|
platelet-derived growth factor (PDGF)
|
|
|
platelets promote the coagulation cascade through
|
the platelet phospholipid complex
|
|
|
von Willebrand factor
|
mediates interaction between platelet surface glycoprotein receptor and subendothelial collagen
|
|
|
platelets release what after adhesion
|
ADP, histamine, serotonin, PDGF
|
|
|
TxA2 is
|
a potent vasoconstrictor and platelet aggregant (made by platelets)
|
|
|
PGI2
|
inhibits further platelet aggregation (made by endothelial cells)
|
|
|
intact endothelial cells oppose coagulation by
|
produce heparin-like molecules, antithrombin III, tissue plasminogen activator, degrade ADP, inactivate thrombin, make protein C and S, make PGI2, make NO
|
|
|
extrinsic pathway of coagulation
|
initiate by tissue factor: factor VII works on IX and X which work on prothrombin which works on fibrinogen (measured by PT time)
|
|
|
intrinsic pathway
|
initiated by contact activation: XII -> XI -> IX -> X -> …
|
|
|
polyploidy
|
chromosome number that is a more than a multiple of 2 of the haploid number, usually results in spontaneous abortion
|
|
|
Down syndrome
|
trisomy 21 accounts for 95% of cases, 5% of cases from Robertsonian translocation, mental retardation, epicanthral folds, acute lymphoblastic leukemia, susceptibility to infection, ~100% incidence of Alzheimer's by age 35, congenital heart disease
|
|
|
Edwards syndrome
|
trisomy 18, mental retardation, micrognathia (small lower jaw), rocker bottom feet, congenital heart disease
|
|
|
Patau's syndrome
|
trisomy 13, mental retardation, microcephaly, cleft lip and palate, fused central face, congenital heart disease
|
|
|
Cri du Chat
|
5p-, high-pitched cry, mental retardation, heart defects
|
|
|
Angelman's syndrome
|
15q-, maternal deletion, stiff ataxic gait with jerky movements, inappropriate laughter, may be two copies of paternal 15 chromosome
|
|
|
Prader-Willi syndrome
|
15q-, paternal deletion, mental retardation, short stature and obesity (with uncontrolled appetite), may be two copies of maternal 15 chromosome
|
|
|
Klinefelter syndrome
|
47, XXY, male hypogonadism, always male phenotype, decreased testosterone, increase FSH, LH, estradiol, tallness, gynecomastia, female distribution of hair
|
|
|
Turner's syndrome
|
45, X, female hypogonadism, most common cause of primary amenorrhea, no Barr bodies seen on buccal smear, usually no retardation, ovaries are replaced by fibrous streaks, short stature/webbed neck, coarctation of aorta coommon
|
|
|
XYY syndrome
|
occurs with increased frequency among criminals demonstrating violent behavior
|
|
|
XXX syndrome
|
usually clinically silent, menstrual irregularities/mild retardation
|
|
|
Fragile X syndrome
|
CGG tandem repeats, 2nd most important cause of hereditary mental retardation (2nd to Down's), macro-orchidism
|
|
|
Huntington's disease
|
CAG repeats
|
|
|
Myotonic dystrophy
|
GCT repeats
|
|
|
Spinal-bulbar muscular atrophy
|
CAG repeats
|
|
|
Adult polycystic kidney disease
|
autosomal dominant, clinically manifests between 30-50 years of age, numerous bilateral cysts
|
|
|
familial hypercholesterolemia
|
autosomal dominant, defect in LDL receptors, early onset of athersclerosis, xanthomas (raised yellow lesions filled with lipid-laden macrophages in the skin and tendons)
|
|
|
hereditary hemorrhagic telangiectasia
|
autosomal dominant, telangiectases of the skin and mucous membranes, recurrent hemorrhages in thos lesions
|
|
|
hereditary spherocytosis
|
autosomal dominant, spheroidal erythrocytes, sequestered and destroyed in spleen, producing hemolytic anemia
|
|
|
Marfan syndrome
|
autosomal dominant, defect of connective tissue (deficiency of fibrillin), tall/thin patients with spiderlike fingers (arachnodactyly), dislocation of ocular lens (ectopia lentis), cystic medial necrosis leading to aortic dilation with aneurysm of the proximal aorta, and dissecting anneurysm of the aorta, loss of connective tissue may lead to mitral valve prolapse
|
|
|
Neurofibromatosis
|
autosomal dominant, multiple neurofibromas of the skin, schwannomas of the 8th nerve, café au lait spots, pigmented iris hamartomas (Lisch nodules), marked by skeletal disorders (such as scoliosis) and increased incidence of other tumors
|
|
|
tuberous sclerosis
|
autosomal dominant, presence of glial nodules and distorted neurons in the cerebral cortex, marked by seizures, mental retardation, associated with renal angiomyolipomas (lesions consisting of malformed blood vessels, smooth muscle, and fat cells)
|
|
|
von Hippel-Lindau disease
|
autosomal dominant, characterized by hemangioblastoma or cavernous hemangioma, adenomas, cysts, associated with increased incidence of renal cell carcinoma, gene for this disease is on the short arm of chromosome 3
|
|
|
Tay-Sachs disease
|
autosomal recessive, lyposomal storage disease, deficiency of hexosaminidase A, accumulates Gm2 gangliosides, characterized by CNS degeneration, blindness, cherry-red spot on macula
|
|
|
Gaucher disease
|
autosomal recessive, lyposomal storage disease, deficiency of glucocerebrosidase, accumulates glucocerebrosides, 3 types, Type 1: hepatosplenomegaly (no CNS involvement) type 2: infantile, severe CNS involvement, death before 1 year of age type 3: juvenile, CNS involvement as well but less severe than type 2
|
|
|
Niemann-Pick disease
|
autosomal recessive, lyposomal storage disease, deficiency of sphingomyelinase, accumulates sphingomyelins, characterized by foamy histiocytes, hepatosplenomegaly, half have cheery red spot in macula similar to Tay-Sachs, death occurs by 3 years of age
|
|
|
Hurler syndrome
|
autosomal recessive, lyposomal storage disease, deficiency of alpha-L-Iduronidase, accumulates heparan sulfate and dermatan sulfate, hepatosplenomegaly, mental retardation, death by 10 years of age
|
|
|
Hunter's syndrome
|
sex recessive, lyposomal storage disease, deficiency of sc-l-iduronosulfate sulfatase, accumulates heparan sulfate and dermatan sulfate
|
|
|
von Gierke disease
|
AR, glycogen storage disease, deficiency of glucose 6 phosphatase, so glycogen accumulates in liver and kidney, hepatomegaly, sometimes intractable hypoglycemia
|
|
|
Pompe disease
|
AR, glycogen storage disease, deficiency a-1,4-glucosidase, accumulates glycogen in liver, heart, skeletal muscle, characterized by cardiomegaly, muscle hypotonia, splenomegaly, death occurs from cardiorespiratory failure before 3 years of age, can have intractable hypoglycemia
|
|
|
Cori disease
|
glycogen storage disease type III, deficiency of the debranching enzyme, amylo-1-6-glucosidase, leading to variable accumulation of glycogen in heart, liver,muscle, so stunted growth, hepatomegaly, hypoglycemia
|
|
|
McArdle syndrome
|
glycogen storage disease type V, deficiency of muscle phosphorylase, painful muscle cramps and muscle weakness following exercise
|
|
|
galactosemia
|
deficiency of galactose-1-phosphate uridyl transferase, failure to thrive, infantile cataracts, mental retardation, cirrhosis, can be prevented by removal of galactose from diet
|
|
|
galactokinase-deficiency galactosemia
|
much less frequent than class galactosemia, usually only marked by infantile catacracts
|
|
|
Phenylketonuria
|
mutation of phenylalanine hydroxylase gene, mental deterioration, mousy/musty body odor, treat with phenyalanine-free diet
|
|
|
alkaptonuria
|
incomplete metabolism of phenylalanine and tyrosine from deficiency of homogentisic oxidase, accumulate homogentisic acid, urine turns black, ochronosis (dark pigmentation of fibraous tissues and cartilage)
|
|
|
Maple Syrup Urine disease
|
defect in keto-dehydrogenase complex, mental and physical retardation
|
|
|
cystic fibrosis
|
mutations in cystic fibrosis transmembrane conductance regulator (chromosome 7), malfunction of exocrine gland, increased viscosity of mucus, increased chloride concentration in sweat and tears, Sweat test, leads to chronic pulmonary disease, pancreatic insufficiency, meconium ileus
|
|
|
Fabry disease
|
x linked disorder, deficiency of alpha galactosidase, accumulate ceramide trihexoside, skin lesions,renal failure
|
|
|
classic hemophilia
|
factor VIII deficiency, hemorrhage from minor wounds and trauma
|
|
|
Lesch Nyhan syndrome
|
deficiency of hypoxanthine-guanine phosphoribosyltransferase, so impaired purine metabolism and excess production of uric acid, characterized by gout, mental retardation, self-mutilation
|
|
|
true hermaphrodite
|
has X and Y chromosomes and both ovarian and testicular tissue, very rare
|
|
|
pseudohermaphrodite
|
has gonads of only one sex but appearance of external genitalia does not correspond with gonads present
|
|
|
anaphase lag
|
results in the loss of a chromosome during meiotic or mitotic division (in early embryonic life, can result in mosaicism)
|
|
|
B cells stay where in lymph nodes and spleen
|
germinal centers of lymph nodes and in the lymphoid follicles of the spleen
|
|
|
T cells stay where in lymph nodes and spleen
|
paracortical and deep medullary areas of lymph nodes and periarteriolar sheaths of the spleen
|
|
|
How can natural killer cells lyse cells
|
via antibody-dependent cell-mediated cytotoxicity
|
|
|
macrophages participate in which type of hypersensitivity reactions?
|
delayed hypersensitivity reactions
|
|
|
What cells have Birbeck granules?
|
Langerhans cells of the skin
|
|
|
What are two antigenn presenting cell types?
|
dendritic cells of lymphoid tissue and Langerhans cells of the skin
|
|
|
What is the complement system?
|
About 20 plasma proteins and their products which can be activated by the classic or alternate pathway to form a final product - the membrane attack complex that lyses target cells
|
|
|
What is the classic complement pathway
|
It is initiated by reaction with antigen-antibody complexes, the final lytic form of activated complement is the result of a series of enzymatic cleavages and recombinations of cleavage products
|
|
|
What is the alternative complement pathway
|
Initiated directly by nonimmunologic stimuli, such as invading microorganisms, and also leads to cleavage products that cause lysis. It bypasses the initial stages of the classic pathway
|
|
|
What is the human leukocyte antigen system?
|
group of related proteins referred to as HLA antigens, the genes that code for these are called histocompatibility genes and are located on the short arm of chromosome 6, known as the major histocompatibility complex (MHC), very important in organ transplantation (HLA typing and matching are now widely used to predict tissue compatibility)
|
|
|
What are class I antigens?
|
These include HLA-A, HLA-B, HLA-C, found on almost all human cells, principal antigens in tissue graft rejection (looked at by killer T cells)
|
|
|
What are class II antigens?
|
HLA-DP, HLA-DQ, HLA-DR antigens, chiefly found on immunocompetent cells (macrophages, dendritic cells, Langerhans cells, B cells, and some T cells)
|
|
|
What is the HLA-B27 antigen associated with?
|
ankylosing spondylitis
|
|
|
Which hypersensitivity reactions require antibody by plasma cells?
|
Types I, II, III
|
|
|
Type IV hypersensitivity reaction is mediated by?
|
T cells and macrophages
|
|
|
Type I hypersensitivity reaction
|
(anaphylactic) - antigen reacts with IgE bound to surface of basophils/mast cells which release histamine and other substances (which are vasoactive, smooth muscle spasm-inducing, or chemotactic) Examples: hay fever, allergic asthma, hives, anaphylactic shock
|
|
|
Type II hypersensitivity reaction
|
(cytotoxic) Antibodies react with antigens that are intrisic components of cell membrane or other structures, resulting in direct damage etc. Examples: warm antibody autoimmune hemolytic anemia, hemolytic disease of the newborn, Goodpasture syndrome, Graves disease
|
|
|
Type III hypersensitivity reaction
|
(immune complex) insoluble complement-bound aggregates of antigen-antibody complexes are deposited in vessel walls or on serosal surfaces or other extravascular sites; neutrophils are chemotactically attracted and release lysozomal enymes etc. Ex. Serum sickness, Arthus reaction, polyarteritis nodosa, SLE, immune complex-mediated glomerular diseases
|
|
|
Type IV hypersensitivity reaction
|
(delayed hypersensitivity) proliferation of antigen-specific CD4+ memory T cells with secretion of IL-2 and other cytokines, recruit and stimulate phagocytic macrophages Ex. Tuberculin reaction, contact dermatitis, tumor cell killing, virally infected cell killing
|
|
|
What are the three methods of Type II hypersensitivity reactions
|
1. complement fixing antibodies (complement results in cell lysis and destruction) 2. antibody dependent cell mediated cytotoxicity (free Fc portion of antibody reacts with cytotoxic leukocytes (especially NK cells) and the target cells are killed) 3. reaction of anti-receptor antibodies with cell-surface receptor protein (ex. Graves disease)
|
|
|
serum sickness
|
systemic deposition of antigen-antibody complexes in multiple sites (especially the heart, joints, and kidneys)
|
|
|
What are the three types of transplant rejection
|
hyperacute rejection, acute rejection, chronic rejection
|
|
|
hyperacture rejection
|
is primarily antibody-mediated, occurs in presence of pre-existing antibody to donor antigens, occurs within minutes, is a localized Arthus reaction marked by acute inflammation, fibirnoid necrosis of small vessels, and extensive thrombosis
|
|
|
acute rejection
|
primarily T-cell mediated, occurs days to months after transplantation, is characterized by infiltration of lymphocytes and macrophages
|
|
|
chronic rejction
|
is primarily caused by antibody-mediated vascular damage, may occur months to years after an otherwise successful transplantation, is characterized by marked vascular fibrointimal proliferation, often resulting in a small, scarred kidney (is becoming more common with the success of immunosuppression in overcoming acute rejection)
|
|
|
Graft versus host disease
|
significant problem in bone marrow transplantation because immunocompetent cells are transplanted in this procedure, can also be caused by whole blood transfusion in patients with severe combined immunodeficiency (SCID), characterized by rejection of host cells by engrafted T and B cells, clinical features: fever, rash, hepatosplenomegaly (principal target organs are liver, skin, and gastrointestinal mucosa)
|
|
|
X-linked agammaglobulinemia
|
X-linked disorder in male infants, failure of antibody synthesis due to block of maturation of pre-B cells to B cells due to a mutation in tyrosine kinase gene, absence of plasma cells, absent or poorly defined germinal centers in lymphoid tissue, therefore recurrent bacterial infections
|
|
|
Isolated IgA deficiency
|
most common inherited B cell defect, inability of IgA B cells to mature to plasma cells, characterized by occasional anaphylacic reactions to transfused blood and infections
|
|
|
Common variable immunodeficiency
|
failure of terminal B cell maturation, resulting in fewer plasma cells and thus hypogammaglobulinemia
|
|
|
DiGeorge syndrome
|
congenital T cell deficiency resulting from aberrant embryonic development of the third and fourth branchial arches, hypoplasia of thymus and parathyroid, failure of T cell maturation, leading to lymphopenia, recurrent viral and fungal infections and tetany from hypoparathyroidism with hypocalcemia
|
|
|
Severe combined immunodeficiency disease (SCID)
|
characterized by marked deficiency of B and T cells, profoudn lymphopenia, occurs in X and AR forms, many AR cases are due to adenosine deaminase deficiency leading to accumulation of deoxyadenosine and deoxy-ATP (toxic to lymphocytes), clinical: severe infections, failure to thrive, graft versus host disease (from blood transfusions), thymic hypoplasia, treat with bone marrow, ADA gene transplantation
|
|
|
Immunodeficiency with thrombocytopenia and eczema (Wiskott-Aldrich syndrome)
|
X-linked, eczema, thrombocytopenia, recurrent infections, and poor antibody response to polysacharide antigens, usually has normal total immunoglobulins
|
|
|
AIDS
|
HIV expressed gp120, binds CD4+ T cells, proviral DNA integrated into host genome, diagnosis by ELISA, paradocxically demonstrate hypergammaglobulinemia from polyclonal B cell activation, opportunistic infections, increased incidence of Kapasi sarcoma
|
|
|
connective tissue (collagen) diseases
|
mostly feature fibrinoid change in connective tissue
|
|
|
SLE
|
prototype connective tissue disease, 80% female, marked by presence of ANAs and extensive immune complex-mediated inflammatory lesions (greatest importance are those in kidney)
|
|
|
clinical manifestations of SLE
|
fever, malaise, lymphadenopathy, weight loss, joint systems, butterfly rash, Raynaud phenomenon, serosal inflammation, diffuse interstitial pulmonary fibrosis, endocarditis, glomerular changes (wire loop appearance, thickening of basement membrane)
|
|
|
lab findings of SLE
|
LE test, ANA tes (reacts with double stranded DNA and Smith antigens), serum complement decreased, false-positive tests for syphilis
|
|
|
Progressive systemic sclerosis
|
(PSS, scleroderma), widespread fibrosis and degenerative changes, marked by ANA anti-Scl-70, ANA with anti-centromere activity is characteristic of the CREST syndrome (calcinosis, Raynoud phenomenon, esophageal dysfunction, sclerodactyl, and telangiectasia)
|
|
|
Clinical manifestations of Progressive systemic sclerosis
|
hypertrophy of collagen fibers (leads to fixed facial appearance), sclerodactyl (claw like hands), Raynoud phenomenon (75% of patients), visceral organ involvement (esophagus, pulmonary fibrosis, hypertension)
|
|
|
Sjogren syndrome
|
xerostomia, keratojunctivitis, one of several connective tissue or other autoimmune disease, most often rheumatoid arthritis (Sicca syndrome only has xerostomia and keratoconjunctivitis), involvement of salivary glands (usually bilaterally enlarged parotids), involvement of lacrimal glands
|
|
|
Clinical findings of Sjogren syndrome
|
ANAs, including the highly specific anti-SS-B
|
|
|
polymyositis
|
chronic inflammatory process especially involving proximal muscles of the extremities (when skin is involved, characteristic reddish-purple rash over exposed face/neck (called dermatomyositis)), characterized by increased serum creatine kinase and usually some ANAs (muscle biopsy demonstrates necrotic muscle)
|
|
|
mixed connective tissue disease (MCTD)
|
mainly female (80%), clinically like other connective tissue disorders expect renal involvement is uncommon, characterized by high-titer anti-nRNP and immunofluorescent speckled nuclear appearance on morphologic ANA analysis)
|
|
|
polyarteritis nodosa
|
immune complex vasculitis characterized by segmental fibrinoid necrosis in the walls of small and medium arteries of almost any organ (mainly in men), antigen (Hep B in 30%, drugs), clinical manifestations: abdominal pain, hypertension, asthma, splenomegaly...)
|
|
|
amyloidosis
|
group of disorders characterized by deposition of amyloid (a proteinaceous material)
|
|
|
amyloid structure
|
not a single substance but a group of substances that share a common physical structure that can be formed by a number of proteins, always in a beta-pleated sheet configuration
|
|
|
amyloid - morphologic features
|
extracellular in distribution, amorphous eosinophilic appearance, characteristically stained by Congo red dye, demonstrating apple green birefriegence
|
|
|
primary amyloidosis
|
caused by deposition of amyloid fibrils derived from immunoglobulin light chains (called AL protein for amyloid light chain), frequently associated with plasma cell disorders such as multiple myeloma and Waldenstrom macroglobulinemia
|
|
|
secondary amyloidosis
|
caused by deposition of AA protein (formed from a precursor SAA (serum amyloid-associated protein which is increased during chronic tissue destruction), usually involves the kidney (nephrotic syndrome common), liver, adrenals, pancreas, lymph nodes, and spleen. Characteristically a comlication of chronic inflammatory disease (such as rheumatoid arthritis, TB, osteomyelitis, syphilis, or leprosy)
|
|
|
Portuguese type of polyneuropathy
|
associated with transthyretin (serum protein that transports thyroxine and retinol), severe peripheral nerve involvement
|
|
|
Alzheimer disease
|
A4 amyloid (also known as amyloid beta-protein), gene that codes for the protein precursors is on chromosome 21
|
|
|
Familial Mediterranean fever
|
AA amyloid, characterized by episodic fever and polyserositis
|
|
|
Medullary carcinoma of the thyroid
|
amyloid protein from calcitonin
|
|
|
Diabetes mellitus
|
deposit of amyloid in islet cells (called amylin or islet amyloid polypeptide (IAPP))
|
|
|
senile amyloidosis
|
transthyretin, found in autopsy of very elderly (no listed clinical signs)
|
|
|
dialysis associated amyloid
|
beta-microglobulin, found in joints of patients undergoing years of hemodialysis (no listed clinical signs)
|
|
|
is dysplasia reversible?
|
yes
|
|
|
carcinoma
|
malignant tumor of epithelial origin
|
|
|
types of carcinoma
|
squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma
|
|
|
adenocarcinoma
|
carcinoma of glandular epithelium, includes malignant tumors of GI mucosa, endometrium, and pancreas, often associated with desmoplasia (tumor-induced proliferation of non-neoplastic fibrous connective tissue)
|
|
|
sarcoma
|
malignant tumor of mesenchymal origin (examples: osteosarcoma, rhabdomyosarcoma, leiomyosarcoma, liposarcoma)
|
|
|
teratoma
|
neoplasm derived from all three germ cell layers (may contain skin, bone, cartilage, teeth, intestinal epithelium), may be malignant or benign, usually arises in the ovaries or testes
|
|
|
papilloma
|
benign neoplasm often arising from surface epithelium, consists of finger-like epithelial processes overlying a core of connective tissue stroma that contains blood vessels
|
|
|
adenoma
|
benign neoplasm of glandular epithelium, consists of two variants: papillary cystadenoma and fibroadenoma
|
|
|
choristoma
|
non-neoplasic area of normal tissue misplaced within another organ (such as pancreatic tissue within the wall of the stomach)
|
|
|
hamartoma
|
non-neoplastic, disorganized, tumor like overgrowth of cell types regularly found in infected organ (example: hemangioma, an irregular accumulation of blood vessels)
|
|
|
Are neoplasms monoclonal or polyclonal?
|
almost all neoplasms are monoclonal, polyclonal proliferations are almost always non-neoplastic
|
|
|
How do carcinomas usually metastasize?
|
via lymphatic spread
|
|
|
How do sarcomas usually metastasize?
|
via blood vessels
|
|
|
clinical manifestation of malignancy
|
1. cachexia and wasting (may be mediated by cachectin (TNF-alpha)) 2. pituitary abnormalities 3. paraneoplastic syndromes 4. oncofetal antigens
|
|
|
prolactinoma
|
pituitary gland tumor, leads to amenorrhea, infertility and sometimes galactorrhea
|
|
|
somatotropic adenoma
|
pituitary gland tumor (acidophilic), leads to gigantism in children and acromegaly in adults
|
|
|
corticotropic adenoma
|
pituitary gland tumor (basophilic usually), leads to Cushing disease (adrenal hypercorticism of pituitary origin
|
|
|
Granulosa-theca cell tumor
|
ovarian abnormality, hyperestrinism
|
|
|
Sertoli-Leydig cell tumor
|
excess androgen production
|
|
|
trophoblastic tissue abnormalities
|
hyperproduction of HcG fromhydatidiformmole or choriocarcinoma
|
|
|
Cushing syndrome
|
caused by production of ACTH-like substances by small cell carcinoma of the lung
|
|
|
Inappropriate secretion of antidiuretic hormone
|
variety of tumors can do this, mainly small cell carcinoma of the lung
|
|
|
Hypercalcemia
|
caused by metastic disease in the bone, secretion of a substance similar to parathormone by squamous cell bronchiogenic carcinoma, or secretion of a substance similar to osteoclast activating factor by the malignant plasma cells of multiple myeloma
|
|
|
Hypoglycemia
|
Secretion of insulin like substances by hepatocellular carcinomas, mesotheliomas, and some sarcomas
|
|
|
Polycythemia
|
caused by elaboration of erythopoietin by renal tumors and other neoplasms
|
|
|
skin lesions
|
includes acanthosis nigricans and dermatomyositis
|
|
|
coagulation abnormalities
|
include migratory thrombophlebtiis associated with carcinoma of the pancreas and other visceral malignancies (Trousseau phenomenon), and disseminated intravascularcoagulation associated with various neoplasms
|
|
|
oncofetal antigens
|
proteins normally only expressed in fetal/embryonic life (includes CEA and AFP)
|
|
|
cocarcinogens
|
when two or more agents work together to cause cancer
|
|
|
promoter
|
a non-carcinogen, that enhances other agent's carcinogenicity
|
|
|
UV radiation carcinogenesis
|
induce dimer formation between thymine pairs, failure of DNA repair can cause cancer (ex. Xeroderma pigmentosum)
|
|
|
ionizing radiation in radiologists
|
skin cancer and myeloid leukemias
|
|
|
ionizing radiation in uranium miners
|
lung cancer
|
|
|
ionizing radiation in head and neck therapy patients
|
thyroid cancer
|
|
|
survivors of atomic blasts
|
acute and chronic myeloid leukemias
|
|
|
radium watch-dial workers
|
osteosarcoma
|
|
|
cigarette smoking
|
carcinoma of the lung, carcinoma of the larynx
|
|
|
excess sun exposure
|
squamous cell carcinoma and basal cell carcinoma of the skin, melanoma
|
|
|
alkylating agents
|
acute leukemia
|
|
|
asbestos
|
carcinoma of lung, pleural and peritoneal mesothelioma, GI tract cancers
|
|
|
smoked foods rich in nitrosamines
|
adenocarcinoma of stomach
|
|
|
alcohol
|
carcinoma of mouth and esophagus, hepatocellular carcinoma
|
|
|
arsenic
|
squamous cell and basal cell carcinomas of skin
|
|
|
low fiber diet
|
adenocarcinoma of colon
|
|
|
high fat diet
|
breast carcinoma
|
|
|
amilyn dies, aromatic amines, beta naphthylamine
|
transitional cell carcinoma of bladder
|
|
|
aflatoxin B2
|
hepatocellular carcinoma
|
|
|
benzene
|
acute leukemia
|
|
|
polyvinyl chloride
|
hepatic hemangiosarcoma (angiosarcoma)
|
|
|
thorotrast
|
hepatic hemangiosarcoma (angiosarcoma)
|
|
|
diethylstilbestrol
|
clear cell adenocarcinoma of vagina
|
|
|
nickel
|
carcinoma of the lung
|
|
|
chromium
|
carcinoma of the lung
|
|
|
uranium
|
carcinoma of the lung
|
|
|
HTLV-1
|
adult T cell leukemia/lymphoma
|
|
|
HPV
|
genital tract neoplasms
|
|
|
EBV
|
nasopharyngeal carcinoma, Burkitt lymphoma
|
|
|
HBV
|
hepatocellular carcinoma
|
|
|
HIV
|
Kaposi sarcoma
|
|
|
Helicobacter pylori
|
adenocarcinoma and B cell lymphomas (MALTomas) of stomach
|
|
|
marasmus
|
low calories
|
|
|
Kwashiorker
|
protein deficiency, normal caloric intake, edema (from lack of albumin production), depigmented bands with pale streaking in hair/skin
|
|
|
B1
|
thiamine, Wernicke-Krsakoff syndrome, wet and dry beriberi
|
|
|
B2
|
riboflavin, cheilosis, glossitis, corneal vascularization, seborrheic dermatitis
|
|
|
B3
|
niacin, pellagra
|
|
|
B6
|
pyridoxine, homocystinuria, pyridoxine-responsive anemia
|
|
|
B12
|
cobalamin, megaloblastic anemia with prominent neurologic dysfunction
|
|
|
folic acid deficiency
|
megaloblastic anemia without neurologic changes
|
|
|
Vit. C
|
Scurvy
|
|
|
Vit. A
|
night blindess
|
|
|
Vit. D
|
Rickets in children, osteomalacia in adults
|
|
|
Vit. E
|
neurologic function
|
|
|
Vit. K
|
hemorrhagic problems
|
|
|
hypervitaminosis A
|
alopecia, hepatocellular damage, bone changes
|
|
|
hypervitaminosis D
|
growth retardation, hypercalciuria, nephrocalcinosis, renal calculi
|
|
|
Wernicke-Korsakoff
|
confusion, ataxia, ophthalmoplegia with memory loss and confabulation
|
|
|
dry beriberi
|
peripheral neuropathy with resultant atrophy of the muscles of the extremities
|
|
|
wet beriberi
|
high-output cardiac failure
|
|
|
pellagra
|
(the three D's) dementia, dermatitis, and diarrhea
|
|
|
Arteriosclerosis
|
general term for three types of vascular disease, all characterized by rigidity and often thickening of blood vessels
|
|
|
Monckeberg arteriosclerosis
|
(medial calcific sclerosis), involves the media of medium-sized muscular arteries, ring like calcifications, does not obstruct arterial flow, results in stiff, calcific "pipestem" arteries
|
|
|
arteriolosclerosis
|
characterized by hyaline, thickening of small arteries and arterioles, especially in the kidneys. Associated with hypertension or diabetes mellitus, 2 varieties (hyaline arteriolosclerosis) andhyperplastic arteriolosclerosis
|
|
|
atherosclerosis
|
fibrous plaques (atheromas) within the intima of arteries
|
|
|
hyaline arteriolosclerosis
|
type of arteriolosclerosis, hyaline thickening of arteriolar walls, called benign nephrosclerosis in kidneys (associated with hypertension)
|
|
|
hyperplastic arteriolosclerosis
|
marked by concentric, laminated, "onionskin" thickening of the arteriolar walls, may be accompanied by necrotizing arteriolitis, in kidneys called malignant nephrosclerosis (associated with malignant hypertension)
|
|
|
atheromas
|
fibrous plaques, have a central core of cholesterol; lipid-laden macrophages (foam cells), necrotic debris, calcium, core is covered by a fibrous cap
|
|
|
Plaques may be complicated by:
|
ulceration, hemorrhage into the plaque, calcification, thrombus formation, embolization
|
|
|
Fatty streak
|
focal accumulations in the intima that may appear as early as the first year of life, can develop into atheromas
|
|
|
most significant consequences of atherosclerosis
|
ischemic heart disease and myocardial infarction (may also cause stroke, ischemic bowel disease, peripheral vascular occlusive disease, renal arterial ischemia, and aneurysms)
|
|
|
Risk factors for atherosclerosis
|
age, gender, hypercholesterolemia, hypertension, diabetes mellitus, cigarette smokin
|
|
|
What is associated with premature atherosclerosis?
|
diabetes mellitus
|
|
|
Reaction to injury to arterial endothelium
|
1. entry of monocytes into subendothelium 2. release of mitogenic factors (platelet dervied growth factor) 3. proliferation and migration of smooth muscle cells into the intima with production of connective tissue matrix proteins 4. monocytes and smooth muscle cells engulf lipid and monocytes turn into lipid laden foam cells (this is mediated by the beta-VLDL receptor)
|
|
|
aneurysms
|
localized abnormal dilations of arteries or veins
|
|
|
Atherosclerotic aneurysm
|
most frequently occurs in the descending (primarily abdominal) aorta
|
|
|
Aneurysms due to cystic medial necrosis
|
most frequent aneurysms of the aortic root
|
|
|
Berry aneurysms
|
small saccular lesions most often seen in the smaller arteries of the brain (unrelated to atherosclerosis), often associated with adult polycystic kidney disease (most frequent cause of subarachnoid hemorrhage)
|
|
|
Syphilitic aneurysm
|
manifestation of tertiary syphilis, caused by syphilitic aortitis, usually involves ascending aorta
|
|
|
Dissecting aneurysm
|
longitudinal intraluminal tear, severe tearing pain/widening of aortic shadow on x-ray, enzymes are normal, usually results in aortic rupture leading to fatal cardiac tamponade, (is usually associated with hypertension or cystic medial necrosis), no relation to atherosclerosis
|
|
|
arteriovenous fistula
|
abnormal communication between artery and vein
|
|
|
phlebothrombosis
|
predisposed by venous circulatory stasis (most often arises in the deep veins of the lower extremities)
|
|
|
spider telangiectasia
|
dilated small vessel surrounded by radiating fine channels, associated with hyperestrinism (seen in chronic liver disease or pregnancy)
|
|
|
hemangiosarcoma
|
rare malignant vascular tumor, associated with arsenic, thorium dioxide, polyvinyl chloride (angiosarcoma of the liver)
|
|
|
Kaposi Sarcoma
|
malignant vascular tumor, epidemic version can be caused by AIDS
|
|
|
polyarteritis nodosa
|
necrotizing immune complex formation of small and medium sized arteries, marked by destruction of arterial medial and internal elastic lamella resulting in aneurysmal nodules, associated with hep. B infection in 30% of patients (can manifest by fever, weight loss, malaise, ab. pain, HA, myalgia, and hypertension). Often accompanied by perinuclear antineutrophil cytoplasmic antibodies P-ANCA's
|
|
|
Churg-Strauss syndrome
|
necrotizing vasculitis consideredby some to be a variant of polyarteritisnodosa, characterized by prominent involvement of pulmonary vasculature, marked peripheral eosinophilia, and clinical manifestations of asthma
|
|
|
Aschoff body
|
rheumatic fever, area of focal interstitial myocardial inflammation, characterized by fragmented collagen and fibrinoid material
|
|
|
Rheumatic fever
|
caused by streptococcal antigens that elicit an antibody response
|
|
|
Rheumatic fever clinical
|
pericarditis, myocarditis, endocarditis (primarily affects mitral valve, then aortic valve), also fever, malaise, increased sed rate, join involvement, skin lesions (erythema marginatum), and CNS involvement
|
|
|
Rheumatic fever affects on valves
|
nonfriable vegetations (verrucae), so not a source of peripheral emboli
|
|
|
Infective endocarditis affect on valve
|
friable vegetations (consist of fibrin, inflammatory cells, bacteria)
|
|
|
acute endocarditis caused by
|
Staph. Aureus in 50%
|
|
|
subacute endocarditis
|
Strep viridans >50% (in patients with congenital heart disease or preexisting valvular heart disease)
|
|
|
infective endocarditis
|
mainly affects mitral valve or mitral with aortic (like RHD), except for intravenous drug users (their tricuspid valve is affected most often)
|
|
|
nonbacterial thrombotic endocarditis
|
associated with debilitating disorders, small deposits on line of closure of valve leaflets, can result in peripheral emboli as well (but emboli are sterile unlike in infective endocarditis)
|
|
|
Libman-Sacks endocarditis
|
occurs in SLE, vegetations on either or both surfaces of the leaflets
|
|
|
endocarditis of the carcinoid syndrome
|
caused by secretory products of carcinoid tumors, results in endocardial plaques of right side of heart (rarely involves left since the lung detoxifies many secretory products)
|
|
|
mitral valve prolapse
|
systolic murmur with a midsystolic click
|
|
|
congestive/dilated cardiomyopathy
|
most common form, 4 chambger hypertrophy and dilation, right and left sided intractable heart failure, often related to alcoholism and thiamine deficiency (beriberi)
|
|
|
restrictive cardiomyopathy
|
infiltrative processes that result in stiffening the heart muscle, exemplified by cardiac amyloidosis
|
|
|
hypertrophic cardiomyopathy
|
hypertrophy of all walls, especially ventricular septum, disoriented,tangled,hypertrophied myocardial fibers
|
|
|
chronic pericarditis
|
characterized by thickening and scarring of pericardium with loss of elasticity, often mimics the signs and symptoms of right sided heart failure
|
|
|
cor pulmonale
|
right ventricular hypertrophy and/or dilation secondary to lung disease, emphysema is a frequent cause
|
