Path

Front 1

What is hypertrophy? When does it occur? What is an example of hypertrophy?

Back 1

Hypertrophy is the increase in tissue or organ size due to an increase in the size of cells. It is an adaptation to increased cellular workload, such as LV hypertrophy in hypertensive heart disease.

Front 2

What is hyperplasia? What is an example of hyperplasia?

Back 2

Hyperplasia is an increase in the number of cells. The glandular proliferation of breast tissue during pregnancy is a classic example. In some cases it can occur in conjunction with hypertrophy, such as uterine enlargement during pregnancy (more and larger cells)

Front 3

What is aplasia? What is the result of aplasia during fetal development?

Back 3

Aplasia is the failure of cell production. Aplasia in fetal development can lead to agenesis (absence) of an organ. In adults, aplasia can be caused by permanent loss of precursor cells, such as bone marrow.

Front 4

What chromosomal syndromes result in gonadal hypoplasia?

Back 4

Turner's (XO) and Klinefelter's (XXY) syndromes both result in hypoplasia of gonadal structures(decreased cell production leading to lack of growth and maturation)

Front 5

What are common causal factors of atrophy (decrease in organ or tissue size due to decreased mass of preexisting cells)?

Back 5

disuse (such as with skeletal muscle), nutritional or oxygen deprivation (such as with decreased blood flow), diminished endocrine stimulation, aging, and denervation are all common causes of atrophy.

Front 6

What are autophagic granules and in what situation are they seen?

Back 6

Autophagic granules are intracytoplasmic vacuoles containing debris from degraded organelles seen with tissue atrophy.

Front 7

What type of metaplasia is associated with vitamin A deficiency? What is another common cause of this type of metaplasia, and what are two examples?

Back 7

Squamous metaplasia, which is also caused by chronic irritation (such as tobacco smoke). Common locations include the respiratory endothelium, the squamocolumnar junction of the cervix, the pancreatic ducts, and the endometrium.

Front 8

What is myeloid metaplasia?

Back 8

Extramedullary hematopoiesis, i.e. proliferation of hematopoietic tissue at sights other than bone marrow, most commonly liver and spleen.

Front 9

What are early stage changes seen in hypoxic cell injury?

Back 9

As aerobic mitochondrial ATP synthesis depends on O2, there is decreased ATP production. This leads to failure of the Na/K pump leading to increased intracellular Na and H2O, causing swelling of the ER, the mitochondria, and the cell as a whole; there is also disaggregation of ribosomes leading to decreased protein synthesis, and there is stimulation of phosphofructokinase activity leading to increased glycolysis which leads to accumulation of lactic acid in the cell.

Front 10

What are late stage changes in hypoxic cell injury?

Back 10

Membrane damage with the loss of phospholipids occurs at both the cell surface and to organelle membranes, leading to morphological changes that include blebbing and myelin figues (whorl like structures)

Front 11

What are the changes seen with irreversible hypoxic cell damage and imminent cell death?

Back 11

There is irreversible cell membrane damage leading to massive Ca influx, extensive calcification of mitochondria, nuclear damage (pyknosis, karyorrhexis, or karyolysis) and disordered degradation of nucleic acids, release of intracellular enzymes and other proteins (such as AST, LDH, troponins, etc), and cell death.

Front 12

What cells are the most sensitive to hypoxia?

Back 12

Neurons, in particular the cerebellar Purkinje cells and hippocampal neurons, suffer irreversible hypoxic damage in as little as 3-5 minutes. Myocardial cells and hepatocytes can last 1-2 hours before permanent hypoxic damage occurs, and skeletal muscles can go many hours before irreversible hypoxic damage occurs.

Front 13

What is the cause of free radical damage in retrolental fibroplasia (retinopathy of prematurity)?

Back 13

Oxygen toxicity

Front 14

What morphological change is seen in liver cells that is a marker of barbituate intoxication?

Back 14

Proliferation and hypertrophy of the SER in hepatocytes

Front 15

What mechanisms exist to degrade free radicals and prevent cell damage?

Back 15

There are both intracellular enzymes (glutathione peroxidase, catalase, superoxide dismutase) as well as antioxidants (Vitamins A,C,E, cysteine, glutathione, selenium, ceruloplasmin, transferrin). There can also be spontaneous decay of free radicals.

Front 16

What type of necrosis has general early preservation of tissue architecture along with cytoplasmic eosinophilia and nuclear changes (pyknosis, karyorrhexis, karyolysis, or disappearance) and where does it tend to occur?

Back 16

Coagulative necrosis, which occurs in organs such as the heart and kidney generally due to sudden blockage of blood flow.

Front 17

What type of necrosis typically occurs following ischemic injury to the CNS? What else can cause this type of necrosis?

Back 17

Liquefactive necrosis, the softening, digestion, and enzymatic liquifactation of tissue, generally occurs in the CNS or with suppurative infections (characterized by pus formation and heterolytic mechanisms)

Front 18

What disease is the most common cause of the formation of necrotic tissue with "cheese-like" consistency?

Back 18

Tuberculosis is the most common cause of caseous necrosis, which in addition to the gross cheese-like consistancy shows amorphous eosinophilic appearance on histological exam. It combines features of both coagulative and liquifactive necrosis and occurs with granulomatous inflammation.

Front 19

What is the difference between wet and dry gangrenous necrosis?

Back 19

Grangrenous necrosis in general most often affects the lower extremities or bowel and is secondary to vascular occlusion. When complicated by heterolytic liquifactive infection, it is called wet gangrene, whereas when it is primarily coagulative necrosis without liquefaction it is dry gangrene.

Front 20

What are the two forms of fat necrosis and where does each occur?

Back 20

Traumatic fat necrosis occurs after injury to tissue with high fat content, such as the breast. Enzymatic fat necrosis is a complication of acute hemorrhagic pancreatitis and involves the diffusing of pancreatic proteases and lipases into the parenchyma causing autodigestion. Fatty acids liberated by these lipases leads to saponification (the formation of soap by forming calcium salts of the fatty acids). Blood vessels are eroded, which leads to hemorrhage.

Front 21

What are morphological features generally seen in apoptosis?

Back 21

single isolated cells or small clusters of cells within a tissue are affected (vs large swaths for necrosis), progression through a series of changes (blebbing, cytoplasmic shrinkin, chromatin condensation, budding into apoptotic bodies, and eventual phagocytosis of these bodies) without inflamation, and eventual involution and shrinkage of cells and cell fragments resulting in small round eosinophilic masses often containing chromatin (such as Councilman bodies in viral hepatitis).

Front 22

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of Tay-Sachs disease?

Back 22

Deficient hexosaminidase A, leading to accumulation of GM2 ganglioside, particularly in nuerons. Autosomal recessive inheritance. Causes CNS degeneration, blindness, cherry red spot on macula, and death before 4 years.

Hint 22

Most common gangliosidosis, Ashkenazi Jews

Front 23

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of Gaucher disease?

Back 23

Deficient glucocerebrosidase leading to accumulation of glucocerebroside in macrophages. Autosomal recessive. Three types (severities) of the disease; Type I - hepatosplenomegaly, erosion of femoral head and long bones; mild anemia. Normal life span possible. Type II - Severe CNS involvement and death before 1 year
Type III - involves both brain and viscera but less severe than type II

Hint 23

Presence of enlarged macrophages with "wrinkled tissue paper" appearance; ie "Gaucher cells"

Front 24

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of Niemann-Pick disease?

Back 24

Deficient in sphingomyelinase OR in cholesterol transport leading to an accumulation of sphingomyelin OR cholesterol in phagocytes . Autosomal recessive inheritance. Causes foamy histiocytes in liver, spleen, lymph nodes, and skin; hepatosplenomegaly, anemia, fever, and in some cases neurological deterioration. About half of cases have cherry red spot in macula. Death by 3 years.

Hint 24

Types A and B are sphingomyelinase related, Type C is cholesterol transport related.

Front 25

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of Hurler syndrome?

Back 25

Deficient in a-L-iduronidase causing accumulation of mucopolysaccharides (heparan sulfate and dermatan sulfate) in heart, brain, liver, and other organs. Autosomal recessive. Leads to progressive deterioration, hepatosplenomegaly, dwarfism, gargoyle like facies, stubby fingers, corneal clouding, progressive mental retardation, and death by 10 years

Hint 25

Clinically similar to--but shouldn't be confused with--Hunter Syndrome

Front 26

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of Von Gierke disease?

Back 26

Deficient in glucose-6-phosphatase, leading to accumulation of glycogen, primarily in the liver and kidney. Autosomal recessive. Leads to hepatomegaly and sometimes intractable hypoglycemia.

Hint 26

Type I glycogenosis

Front 27

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of Pompe disease?

Back 27

Deficient in a-1,4-glucosidase leading to accumulation of glycogen, especially in the liver, heart, and skeletal muscles. Autosomal recessive. Leads to cardiomegaly, muscle hypotonia, splenomegaly, sometimes intractable hypoglycemia. Death occurs by 3 years due to cardiorespiratory failure.

Hint 27

Type II glycogenosis (also classified as a lysosomal storage disease)

Front 28

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of Cori disease?

Back 28

Deficient in the debranching enzyme amylo-1,6-glucosidase. Causes variable accumulation of glycogen in the liver, heart, or skeletal muscle. Autosomal recessive. Leads to stunted growth, hepatomegaly, hypoglycemia.

Hint 28

Type III glycogenosis

Front 29

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of McArdle syndrome?

Back 29

Deficient in muscle phosphorylase causing accumulation of glycogen in skeletal muscle. Autosomal recessive. Leads to painful muscle cramps and weakness following exercise.

Hint 29

Type V glycogenosis

Front 30

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of classic (severe) galactosemia?

Back 30

Deficiency of galactose-1-phosphate uridyl transferase causing accumulation of galactose-1-phosphate in many tissues. Autosomal recessive. Leads to failure to thrive, infantile cataracts, mental retardation, and progressive hepatic failure leading to cirrhosis and death. Most can be prevented by removing galactose from the diet.

Hint 30

Less frequent form is caused by galactokinase deficiency, often marked only by infantile cataracts.

Front 31

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of PKU?

Back 31

Defiency of phenylalanine hydroxylase resulting in the failure of conversion from Phe-->Tyr in the liver. Accumulation of Phe and ketone metabolites from alternate catabolic pathways occurs. Autosomal recessive. Leads to mental deterioration, seizures, hyperactivity, decreased pigmentation (blue eyes, blond hair), mousy or musty body odor (from phenylacetic acid in sweat). Screened for on the 3rd or 4th day after birth (false negatives earlier), treatment is Phe-free diet.

Hint 31

PKU mother not following diet can cause congenital heart disease, growth retardation, microcephaly, and mental retardation in non-PKU infant.

Front 32

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of alkaptonuria?

Back 32

Deficiency of homogentisic oxidase causing incomplete metabolism of Phe and Tyr, leading to accumulation and urinary excretion of homogentisic acid. Autosomal dominant. Urine turns dark and finally black upon standing, dark pigmentation of fibrous tissues and cartilage (ochronosis) and incapacitating arthritis, occasional involvement of heart valves.

Front 33

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of maple syrup urine disease?

Back 33

Deficiency/defect in any of the proteins that make up the branch chain a-keto acid dehydrogenase complex that leads to high levels of keto-acids of leucine, isoleucine, and valine. Autosomal recessive. Urine has "burnt sugar" or "maple syrup" odor as well as high levels of Leu, IsoLeu, and Val ketoacids, leads to mental and physical disabilities and often leads to neonatal death. Can be detected on newborn screening and severity minimized by protein-modified diets.

Front 34

What are the deficiency, genetics, mode of inheritance, and presenting characteristics of cystic fibrosis?

Back 34

Mutation to the CFTR gene found on long arm of chromosome 7. Gene codes for a membrance protein facilitating movement of Cl and other ions across membranes. In 70% of cases, the cause involves the deletion of three base pairs coding for Phe at position 508 (ΔF508). Autosomal recessive. Leads to malfunction of exocrine glands, increased viscosity of mucus, increased chloride concentration of smeat and tears. Clinically, manifests as chronic pulmonary disease (chronic bronchitis, recurrent pneumonia, bronchiectasis, lung abscesses), pancreatic insufficiency leading to malabsorption and steatorrhea, and meconium ileus (obstruction of the small bowel in the newborn cause by thick, viscous meconium ie first stool). Sweat test important diagnostic (normal secretion, abnormal reabsorption of chloride into sweat glands ie saltier sweat)

Hint 34

P. aeruginosa infections most common cause of death. Most common lethal mutation in Caucasians.

Front 35

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of Hunter syndrome?

Back 35

L-iduronosulfate sulfatase deficiency leading to accumulation of heparan and dermatan sulfates. X-linked recessive. Leads to hepatosplenomegaly, micrognathia, retinal degeneration, joint stiffness, mild mental retardation, and cardiac lesions

Hint 35

Clinically similar, but less severe, than Hurler syndrome

Front 36

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of Fabry disease?

Back 36

Deficiency of a-galactosidase A leading to accumulation of ceramide trihexoside in body tissues. X-linked recessive. Leads to skin lesions (angiokeratomas) on the lower trunk, febrile episodes, severe burning pain in extremities, and cardiovascular and cerebrovascular involvement. Death in early adult life due to renal failure.

Front 37

What are the mutation/deficiency, genetics, mode of inheritance, and presenting characteristics of Hemophilia A?

Back 37

Deficiency in clotting factor VIII. X-linked recessive, gene location linked to the tip of the long arm of the X chromosome. Causes hemorrhage to minor wounds and trauma, bleeding from oral mucosa, hematuria, hemarthroses (which can lead to crippling deformities from recurrence)

Hint 37

Classic hemophilia

Front 38

What are the enzyme deficiency, accumulated material, mode of inheritance, and presenting characteristics of Lesch-Nyhan syndrome?

Back 38

Deficiency in HGPRT leading to impared purine metabolism and excess production of uric acid. X-linked recessive. Leads to gout, mental retardation, choreoathetosis (abnormal involuntary movements), spasticity, self-mutilation, and aggressive behavior.

Front 39

What are the defect, characteristics, and mode of inheritance of adult polycystic kidney disease?

Back 39

Numerous bilateral cysts replace and destroy renal parenchyma. Manifests between 20 and 40 years, death usually occurs by 50 years. Associated with berry aneurysms. Autosomal dominant.

Hint 39

Most frequently occurring hereditary renal disorder

Front 40

What are the defect, characteristics, and mode of inheritance of familial hypercholesterolemia?

Back 40

Anomalies of LDL receptors leading to decreased LDL uptake into cells. Causes hyperlipidemia with increased atherosclerosis and xanthomas in skin and tendons. Autosomal dominant.

Hint 40

Homozygous FH manifests in more extreme, earlier disease.

Front 41

What are the defect, characteristics, and mode of inheritance of hereditary hemorrhagic telangiectasia?

Back 41

Rare autosomal dominant disorder seen with increased frequency in certain populations (eg mormons in Utah). Characterized by localized telangiectases of the skin and mucous membranes and recurrent hemorrhage from these lesions.

Hint 41

Also known as Osler-Weber-Rendu syndrome

Front 42

What are the defect, characteristics, and mode of inheritance of hereditary spherocytosis?

Back 42

Caused by a variety of defects in erythrocyte membrane-associated skeletal proteins (Spectrin, ankyrin). Leads spherical RBCs that are sequestered and destroyed by the spleen, leading to hemolytic anemia. Autosomal dominant. Splenectomy curative.

Hint 42

Increased MCHC. Confirmed with osmotic fragility test.

Front 43

What are the defect, characteristics, and mode of inheritance of Marfan syndrome?

Back 43

Defect in fibrillin leading to connective tissue disorders. Tall, thin patients with pectus excavatum, abnormally long limbs, spider-like fingers, hyperextensible joints; dislocation of the ocular lens (ectopia lentis); Cystic medial necrosis of aorta-->aortic aneurysm, aortic valve deficiency, aortic dissection, as well as mitral valve prolapse can occur. Autosomal dominant.

Front 44

What are the defect, characteristics, and mode of inheritance of neurofibromatosis type 1?

Back 44

Mutation of the NF1 gene on long arm of chromosome 17, a tumor suppressor gene encoding a GTPase activating protein (GAP) that facilitates conversion of active ras-GTP to inactive ras-GDP. Leads to multiple neurofibromas in skin and other locations (which may evolve into malignant tumors), schwannomas of the 8th nerve, cafe au lait spots, and pigmented iris hamartomas (Lisch nodules); skeletal disorders such as scoliosis, bone cysts; increased incidence of tumors (especially pheochromocytoma, Wilms tumor, rhabdomyosarcoma, and leukemia). Autosomal dominant.

Hint 44

Also known as von Recklinghausen disease. Type 2 has bilateral acoustic neuroma, juvenile cataracts, caused by NF2 gene on chromosome 22

Front 45

What are the defect, characteristics, and mode of inheritance of tuberous sclerosis?

Back 45

Glial nodules and distorted neurons in the cerebral cortex, seizures, mental retardation, adenoma sebaceum (facial skin lesion), rhabdomyoma of heart, renal cysts. Autosomal dominant (but with incomplete penetrance, variable presentation)

Front 46

What are the defect, characteristics, and mode of inheritance of von Hippel-Lindau disease?

Back 46

Associated with deletion of VHL (a tumor supressor) gene on chromosome 3. Hemangioblastomas of retina/cerebellum/medulla; cysts of liver, kidney, pancreas, other organs; high incidence of renal cell carcinoma. Autosomal dominant.

Front 47

What are the defect, characteristics, and mode of inheritance of achondroplasia?

Back 47

Defect of fibroblast growth factor (FGF) receptor 3. Results in dwarfism- short limbs, trunk and head normal size. Autosomal dominant.

Hint 47

Associated with advanced paternal age.

Front 48

What genetic disorders are considered "balanced polymorphisms" and in relation to what diseases?

Back 48

Hemoglobin S (homozygous causes sickle cell disease, heterozygous protective vs P. falciparum malaria); G6PD deficiency (X linked; carriers have both oxidant related hemolytic anemia--bad--and malaria resistance--good); PKU (lower incidence of spontaneous abortion as modest increase in Phe thought to be protective affect on pregnancy); Tay-Sachs (potentially protective vs TB); Cystic fibrosis (protective against cholera-insufficient chloride channels to cause water loss)

Hint 48

balanced polymorphism = homozygous causes disease but heterozygous may give survival benefit, leading to higher rates of the mutation in certain populations. Occurs in both X-linked and autosomal disorders.

Front 49

What are the genetics and characteristics of cri du chat syndrome?

Back 49

Deletion of the short arm of chromosome 5 (5p-) causing severe mental retardation, microcephaly, low birth weight, round face, wide set eyes, low set ears, epicanthal folds, and the unusual cat-like cry the disorder is named for.

Hint 49

"cry of the cat" or 5p- syndrome

Front 50

What are the genetics and characteristics of Down syndrome?

Back 50

Trisomy 21 (95%) or translocation with material from chromosome 21 found on a different chromosome causing effective trisomy 21 (5%). Maternal non-disjunction primary cause (older maternal age associated), when paternal non-disjunction no age association. Mental retardation, characteristic appearance, Brushfield spots (white spots on periphery of iris), simian crease on palm. Complications include leukemia (most often ALL), congenital heart disease (ASD, AV valve malformations, etc), susceptibility to infections, early onset Alzheimer-like brain changes.

Hint 50

Most frequently occurring chromosomal disorder.

Front 51

What are the genetics and characteristics of Edwards syndrome?

Back 51

Trisomy 18 (most frequently from non-disjunction). Results in mental retardation, micrognathia, low set ears, rocker-bottom feet, finger flexion deformities, congenital heart disease.

Front 52

What are the genetics and characteristics of Patau syndrome?

Back 52

Trisomy 13. Results in mental retardation, microcephaly, microphthalmia, brain abnormalities, cleft lip/palate, polydactyly, rocker-bottom feet, congenital heart disease.

Front 53

What are the genetics and characteristics of fragile X syndrome?

Back 53

Increased CGG repeats in the 5' untranslated region of the X chromosome (number can increase during oogenesis, cause more severe disease ie anticipation). X-linked but with unusual patterns of inheritance (unaffected male carriers-premutations; affected daughters-selective X inactivation?) Second most common cause of mental retardation, also causes enlarged testes, mandible

Hint 53

premutations only expand during oogenesis; male carriers pass premutation on to daughters who then may expand, pass full mutation on to children.

Front 54

What are the genetics and characteristics of DiGeorge/velocardiofacial syndrome?

Back 54

Microdeletion of 22q11. Cardiac abnormalities, abnormal facies, T-cell deficit because of thymic hypoplasia, cleft palate, hypocalcemia because of hypoparathyroidism, and in 30% behavior disorders/psychosis that develop during adolesence

Hint 54

CATCH 22 syndrome

Front 55

What is the classic pathway of compliment activation?

Back 55

Initiated by reaction with antigen-antibody complexes. Final MAC of activated compliment is the result of a series of enzymatic cleavages and recombination of cleavage products.

Front 56

What is the alternate pathway of compliment activation?

Back 56

Initiated by nonimmunologic stimuli (ie doesn't require antibody-antigen complex) and eventually leads to MAC. It bypasses the early stages of the classic pathway.

Front 57

Type I hypersensitivity reaction

Back 57

Antigen crosslinks cell surface immunoglobulin E molecules and mediates the degranulation of mast cells and basophils leading to histamine release. This increases vascular permeability; other vasoactive substances also produced. Chemotactic substances recruit eosinophils, resulting in peripheral eosinophilia. Examples include allergic rhinitis, anaphylactic shock, angioedema (swelling of lips/eyelids/etc)

Hint 57

anaphylaxis/immediate hypersensitivity

Front 58

Type II hypersensitivity reaction

Back 58

Antibody mediated - IgG/IgM bind to antigen on cell surface and fix compliment, cause antibody depended cell-mediated cytotoxicity (esp NK cells), or react will cell surface receptors to inappropriately stimulate. Antigens usually localized in tissue basement membrane or blood cell membrane. Serum compliment decreased with compliment fixing variety. Examples include hemolytic anemia, Goodpasture's syndrome, Grave's disease, myasthenia gravis, etc.

Hint 58

anti-receptor antibody stimulation of cell surface receptors sometimes classified as "Type V sensitivity"

Front 59

Type III hypersensitivity reaction

Back 59

Antibody-antigen complex formation and often deposition. Complexes bind compliment (chemotactic for PMN) leading to lysosomal enzyme release, tissue damage. Decreased serum compliment. Also, Factor XII activated (thrombosis, activation of kinin system-->vasodilation and edema), platelet aggregation with release of vasoactive amines. Examples include serum sickness, SLE, Arthus reaction, PAN, immune complex mediated glomerular disease (eg post-strep glomerulonephritis)

Hint 59

immune complex hypersensitivity

Front 60

Type IV hypersensitivity reaction

Back 60

Delayed hypersensitivity. T-cell receptor of CD4 lymphocytes interact with antigen presented by macrophages, stimulate CD4 memory T cells that can proliferate and secrete cytokines on later contact with antigen; secreted IL-2 and other cytokines recruit and stimulate phagocytic activity of macrophages. Examples include DM type I, PPD test, contact dermatitis, MS

Hint 60

cell-mediated hypersensitivity

Front 61

Hyperacute transplant rejection

Back 61

Due to preformed antibodies against transplant. Occurs within minutes. Localized Arthus reaction (Type III sensitivity) with acute inflammation, fibrinoid necrosis of small vessels, extensive thrombosis.

Front 62

Acute transplant rejection

Back 62

Primarily cytotoxic T-cell mediated rejection directed against foreign MHCs occurring days to weeks after transplantation. Characterized by infiltration with lymphocytes and macrophages. Reversible with immunosuppression (cyclosporin, OKT3)

Front 63

Chronic transplant rejection

Back 63

Antibody mediated vascular damage (fibroid necrosis/fibrointimal proliferation) occurring months to years after transplantation. Irreversible (ie can't be prevented by immunosuppression). Becoming more common as acute rejection is better prevented.

Front 64

Graft-vs-Host disease

Back 64

Immunocompetent lymphocytes in transplanted bone marrow (or whole blood transfusion in SCID) attack the host cells, resulting in severe organ disfunction. Liver, skin, and GI mucosa are primary targets. Major symptoms include maculopapular rash, jaundice, hepatosplenomegaly, and diarrhea.

Front 65

What are the cause, characteristics, and effects of Bruton's agammaglobulinemia?

Back 65

X-linked mutation in the B cell tyrosine kinase (Btk) gene blocking maturation of pre-B cells into B cells. Leads to the absence of serum immunoglobulins (all classes) after 6 months (decline of maternal IgG). Absent or poorly developed germinal centers in lymphoid tissue, lack of plasma cells. Leads to recurrent bacterial infections (pneumococci, strep, staph, Haemophilus) but viral or fungal resistance (cell-mediated immunity) and neutrophil function are unaffected

Front 66

What is the most common selective immunoglobulin deficiency?

Back 66

IgA deficiency, which may be associated with sinus and lung infections, diarrhea, and milk allergies. Possibly due to a defect in isotype switching.

Hint 66

Mucosal surfaces are vulnerable to infection

Front 67

What deficiency occurs in common variable immunodeficiency?

Back 67

B-cell terminal maturation (to plasma cells) is defective, leading to hypogammaglobulinemia with recurrent bacterial infections. This disorder can be acquired in the 20s-30s.

Hint 67

Normal number of circulating B cells

Front 68

What immune defect is associated with hypocalcemia, tetany, cleft palate, and cardiac defects? What is the cause?

Back 68

T-cell deficit due to thymic hypoplasia resulting in recurrent viral and fungal infections is associated with DiGeorge syndrome (CATCH 22 syndrome) caused by the microdeletion 22q11. It is a failure of development of the 3rd and 4th pharyngeal pouches.

Front 69

What is the result of ADA (adenosine deaminase) deficiency?

Back 69

ADA deficiency leads to the accumulation of deoxyadenosine and deoxy-ATP, both of which are toxic to lymphocytes. This leads to severe deficiency of both T and B cells and major defects in immunity, ie SCID. Severe infections of all types, high incidence of malignancy, failure to thrive, and graft-vs-host disease (as a result of transfusions) are all clinical manifestations of the disease. Additionally, there is hypoplasia of lymphoid tissue (including thymus). Treatment is bone marrow or stem cell transplantation; possibly gene therapy? (currently on hold)

Hint 69

Autosomal recessive. Responsible for approximately half of cases. Numerous other autosomal and X-linked causes.

Front 70

What X-linked disorder is characterized by eczema, thrombocytopenia, recurrent infection, and poor antibody response to polysaccharide antigens?

Back 70

Wiskott-Aldrich syndrome, which is associated with elevated IgA, normal IgE, and low IgM levels (with the inability to mount IgM response vs polysaccharide capsular antigens).

Front 71

What immune problem is associated with ataxia and spider angiomas, and what is the cause?

Back 71

A defect in DNA repair enzymes leads to IgA deficiency, as well as cerebellar problems and telangiectasia.

Hint 71

ataxia-telangectasia

Front 72

What immune defect predisposes an individual to infection with Staphylococci but not Streptococci? What immune cell is affected, and how? What is the inheritance pattern of this disease?

Back 72

A defect in NADPH oxidase (X-linked) or related enzymes (which may be autosomal recessive) leads to neutrophils with the inability to produce the oxidative burst that kills bacteria. Catalase positive bugs (S. aureus, E. coli, Aspergillus) are ingested but destroy the small amount of H2O2 produced during metabolism, preventing myeloperoxidase-halide system killing. Catalase negative bugs (Streptococci, etc.) don't have catalase, so the small amount of H2O2 produced during metabolism is then used against them by the neutrophil.

Hint 72

Chronic Granulomatous Disease of Childhood

Front 73

A partial albino patient with cranial and peripheral neuropathies presents with recurrent infections of strep and staph. What defect is present?

Back 73

Abnormal WBC characterized by abnormal microtubule formation (affecting movement) with impaired chemotaxis and migration. They also have large cytoplasmic granules (abnormal lysosomes/melanosomes in melanocytes) caused by impaired membrane fusion.

Hint 73

Chediak-Higashi syndrome/disease

Front 74

What immune deficiency leads to recurrent early severe pyogenic and fungal infections and a delayed separation of the umbilicus?

Back 74

A deficiency in adhesion proteins (B2 integrin of LFA-1) on phagocytes, imparing migration. Type II is similar, with the defect is related to the synthesis of sialyl-Lewis C on neutrophils

Hint 74

Leukocyte adhesion deficiency syndrome

Front 75

What is the result of failed g-interferon production by helper T cells? What are the features of this disease?

Back 75

Neutrophils fail to respond to chemotactic stimuli, leading to "cold" abscesses (particularly staph), as well as eczema, coarse facies, retained primary teeth, high levels of IgE (and often eosinophilia).

Hint 75

Job's syndrome

Front 76

What is the result of deficient C3? Deficient C6-C8? Deficient decay accelerating factor (DAF)?

Back 76

C3 deficiency leads to severe recurrent pyogenic sinus and respiratory tract infections. C6-C8 deficiencies predispose to Neisseria bacteremia (remember meningitis). DAF deficiency leads to paroxysmal nocturnal hemoglobinuria.

Hint 76

hypocomplimentemias

Front 77

8;14 translocation

Back 77

Increased expression of c-myc due to association with Ig heavy chain locus and regulatory sequences. Associated with Burkitt lymphoma.

Front 78

14;18 translocation

Back 78

Ig heavy chain locus transposed to a site adjacent to bcl-2, leading to enhanced production and resulting inhibition of apoptosis. Associated with follicular lymphomas.

Front 79

9;22 translocation

Back 79

"Philadelphia chromosome". c-abl protooncogene is transposed to a site adjacent to bcr oncogene on chromosome 22, creating bcr-abl fusion protein with increased tyrosine kinase activity. Associated with CML.

Front 80

15; 17 translocation

Back 80

translocation of PML gene with retinoic acid receptor-a (RAR-a) gene. Therapy with all-trans retinoic acid can result in remission of disease. Associated with acute promyelocytic leukemia (type of AML)