Test 2 10 In '10

Front 1

1.Affects 1:50,000 male live births; females are carriers

2. Maps to Xq28; 80% of affected individuals have mutation in MTM1 gene  encodes myotubularin protein  lipid phosphatase

3. First identified in 1966 by muscle biopsy showing centrally located nucleus in skeletal muscle that resembles the fetal stage of muscle development

4. Diagnosed by “floppy” male infant followed by needle biopsy

5. Characterized by neonatal low muscle tone w/ delayed developmental milestones (esp. head control, crawling, & walking)

6. Usually fatal in first 2 years of life due to respiratory failure.

7. Currently no cure

Back 1

X-linked Myotubular Myopathy (OMIM at NCBI)

Front 2

1. X-linked recessive disorder (Xp21)  mutation in gene that encodes dystrophin  results in progressive muscular weakness (no longer able to anchor actin to extracellular matrix)

2. Disruption of sarcolemma  entry of Ca2+ into muscle cell  necrosis of muscle fiber

3. Primarily affects males – onset between 3-5 years of age; no cure; unable to walk by 12; require respirator to breath by age 20

4. Laboratory finding is increased serum creatine kinase levels

5. Muscular dystrophies heterogeneous group of congenital muscle diseases characterized by severe muscle weakness, atrophy & destruction of muscle fibers. caused by genetic defects in muscle transmb proteins linking dystrophin to laminin

Back 2

Duchenne’s muscular dystrophy

Front 3

1. Food poisoning caused by Clostridium botulinum toxin (BOTOX)  inhibits ACh release at neuromuscular junctions

2. Characterized by muscle paralysis, vomiting, nausea, & visual disorders

3. Fatal if untreated; treatment – hospitalization, antibiotics, antitoxin (antidote to botulinum toxin)

Back 3

Botulism

Front 4

1. Autoimmune disease; α-ACh receptor antibodies produced

2. Abs bind & block access of ACh to receptor  blocking normal nerve-muscle interaction

3. Progression of disease associated w/ decrease in # of neuromuscular junctions

4. Characterized by extreme muscle weakness, decrease in number of neuromuscular junctions, ptosis (drooping upper eye lid) & diplopia (single object seen as two)

5. Treatment: AChase inhibitors

Back 4

Myasthenia gravis

Front 5

1. Most common type of childhood sarcoma; can occur anywhere in body; in US ~ 350 children diagnosed/year

2. 3 types:
a. Embryonal – most common; occurs most often in head, neck, genital or urinary regions
b. alveolar – common during teens; occurs in arms, legs, chest, abdomen, genital or anal regions
c. anaplastic – rare in children

3. Symptoms include: lump or swelling that continually increases in size, eye bulging, headache, problems urinating or with bowel movements, blood in urine, bleeding in nose, throat, vagina or rectum; histology positive for IF desmin

4. Treatment: surgery, radiation therapy and chemotherapy; new treatments include: high dose chemotherapy with stem cell transplant (blood, bone marrow)

Back 5

Rhabdosarcoma – cancer arising from striated muscle

Front 6

1. Autosomal dominant/recessive mutation in ryanodine receptor
2. Onset – congenital; symptoms – poor muscle tone and weakness in infants; delay in attainment of motor milestones; skeletal deformities (joint dislocations & scoliosis)
3. Patients susceptible to malignant hyperthermia with some anesthetics
4. H&E appearance – faint central abnormality in myofibers; Myosin ATPase stain reveals central round areas devoid of staining

Back 6

Central Core Disease (group of disorders)

Front 7

1. Congenital, herediatary disease (1:50,000) due to mutations in nebulin
2. Characterized by delayed motor development, muscle weakness in arms, legs, trunk, throat, and face muscles (usually non-progressive)
3. Trunk muscle weakness leads to respiratory issues without therapy and/or intervention
4. Histology – muscle biopsy reveals thread-like rods called nemaline bodies (positive for actin and α-actinin)
5. No cure

Back 7

Nemaline myopathy

Front 8

1. Autosomal recessive & dominant forms
2. Mutation in desmin that prevents its forming intermediate filament rods; instead forms intracytoplasmic desmin aggregates in skeletal & cardiac muscle
3. Desmin normally found around Z-line; connects Z-lines to cytoskeleton underlying plasma membrane; signaling thru desmosomes
4. Histology – sarcomers misaligned; loss of Z-lines and normal striated appearance; muscle cells die by apoptosis and necrosis; desmin inclusion bodies in skeletal and cardiac muscles
5. Characterized by weakness and atropy of distal muscles of legs, arms, trunk and neck
6. Respiratory issues due to trunk muscle weakness and loss
7. ~60% of patients also have cardiac involvement; most patients ultimately require wheelchair, walker, etc.

Back 8

Desmin-related myopathy

Front 9

1. Irreversible necrosis of cardiac muscle cells due to prolonged ischemia (> than 20 mins).
2. Detect lactic dehydrogenase-1 and creatine kinase in serum.
3. Fatal if extensive damage to cardiac muscle
4. Treatment: bypass surgery

Back 9

Myocardial infarction

Front 10

1. Loss of acid maltase in muscle  inability to process carbohydrates
2. Affects storage and breakdown of glycogen in lysosomes (AKA lysosomal storage disease)
3. In absence of acid maltase, glycogen accumulates & is not converted to glucose
4. Onset in infants – usually fatal by 2; child & adult onset less severe
5. Characterized by slow progressive weakness in respiratory muscles, hips, upper leg & arms, shoulders; cardiac involvement in childhood forms

Back 10

Pompe’s Disease (Acid maltase deficiency)

Front 11

N. fowleri (a protist, sometimes called the “brain-eating ameba”) invade the cental nervous system via the nose, more specifically the olfactory mucosa and cribriform plate of the nasal tissues. The penetration initially results in significant necrosis of and hemorrhaging in the olfactory bulbs. From there, amoebae climb along nerve fibers through the floor of the cranium via the cribriform plate and into the brain. The amoebae begin to consume the cells of the brain piecemeal by means of a unique sucker apparatus extended from their cell surface. It then becomes pathogenic, causing primary amoebic meningoencephalitis (PAM). PAM is a syndrome affecting the central nervous system, characterized by changes in olfactory perception (taste and smell), followed by vomiting, nausea, fever, headache, and the rapid onset of coma and death in two weeks. N. fowleri are present in Oklahoma lakes and fresh water areas.

Back 11

Naegleria (pronounced nəˈɡlɪəriə) fowleri infection

Front 12

Maxillary sinus most often involved in adults,
ethmoid sinus in children.
Some Causes: Blockage of drainage via paralysis of ciliary elevator or viral/bacterial upper respiratory infection or deviated septum. Results in fever, nasal congestion, pain over sinus. Sinuses become congested with mucous and bacterial growth.

Back 12

Sinusitis

Front 13

see Box 19.2 and ppt. Also note that nasal polyps are associated with disease. Nasal polyps in a child warrant a sweat test to rule out disease. Known also as chronic pulmonary disease. It involves production of a defective transmembrane conductance regulator (CFTR) for chloride ions. The CFTR Cl- is degraded in the Golgi apparatus due to defective protein folding. Loss of CFTR Cl- causes decreased Na+ and Cl- reabsorption in sweat glands. In other epithelial cells (i.e. bronchus epithelium, pancreatic duct cells), Na reabsorption from the lumen is increased causing movement of water into the cell. This results in a thick mucous secretion. Some ciliary dyskinesia present, expressed as infertility in males (95%).

Back 13

Cystic Fibrous

Front 14

Decreased surfactant in fetal lungs
-Caused by prematurity, maternal diabetes, Cesarean section – lack of stress-induced increase in cortisol from a vaginal delivery

2. Widespread atelectasis results in massive intrapulmonary shunting

3. Collapsed alveoli are lined by hyaline membranes

Decreased synthesis of surfactant resulting in ______. Causes: Prematurity, Maternal diabetes, Cesarean Section; Gross: Purple-Red Lungs; Microscopic: eosinophiles lined by hyaline membranes. Formerly called hyaline membrane disease. Due to an inadequate supply of surfactant at birth which can be related to deficient surfact production or failure of Type II pneumocytes to develop and mature. Signs include cyanosis and labored breathing, caused by inability of pulmonary alveoli to expland or remain open after inspiration. On gross evaluation, the lungs appear airless and ruddy (liverlike). The lungs require more pressure to inflate. Diffuse atelectasis occurs initially and progresses. The lack of oxygen damages endothelial cells and pneumocytes and this results in exudation of a fibrinous matrix from the blood. This matrix accumulates and creates a thick "hyaline membrane" lining the ______, visible with light microscopy. These hyaline membranes are formed within a half hour after birth. Some healing or regeneration of Type II cells can occur within 36-72 hours.
Type II cells then give rise to surfactant. Also see ppt.

Back 14

Infant Respiratory Distress Syndrome (RDS)

Front 15

condition of the lung characterized by permanent enlargement of the air spaces distal to the terminal bronchiole. Enlargement is caused by chronic obstruction of airflow, most often because or narrowing of the bronchioles, accompanied by destruction of the alveolar wall.

specific deficiency causes severe form in both heterozygos and homozygos. Severe because it replaces the cartilage (elastic fibers) with connective tissue

Back 15

α1-Antitrypsin Deficiency leading to Emphysema

Front 16

ARDS – Adult Respiratory Distress Syndrome

Back 16

see notes

Front 17

loss of lung volume due to inadequate expansion of the air spaces
(collapse).

Back 17

Atelectasis (at-e-lek-ta-sis)

Front 18

Alveoli fill with exudates containing wbcs and rbcs, referred
to as hepatization (understand this better once we talk about liver in this section) because the lung
resembles the liver. The lung has enlarged capillaries giving it a red color. The lung lacks alveoli or
alveoli that that are functional because they are swollen or filled with neutrophils, rbcs, and fibrin. See Box 19.3b.

Back 18

Early Stages of Acute Pneumonia

Front 19

A malignant tumor that originates in the mesothelial lining of the serous membranes (pleura, peritoneum, pericardium). 90% of malignant mesotheliomas are pleural mesotheliomas. Pleural mesothelioma is associated with long time exposure (25 to 40 yrs) to asbestos. Pleural mesothelioma can spread to pericardium and diaphragm and can invade the subpleural lung tissue and metastasize to any organ. Imaging of the thorax detects thickening of the pleura and/or asbestos plaques. No etiologic relationship with smoking. Symptoms include pleural effusion (abnormal liquid in the pleural space), chest pain, dyspnea. (see ppt for gross image).

Back 19

Mesothelioma

Front 20

Permanent dilation of the bronchi and bronchioles, due to destruction of cartilage and elastic tissue by an infection; Causes: CF, TB, obstruction by a carcinoma, primary
ciliary dyskinesia; most common in lower lobes (see ppt for gross image).

Back 20

Bronchiectasis

Front 21

A disease of large and muscular (medium-sized) arteries that results in the progressive accumulation within the intima of smooth m. cells, lipids, and CT.

initial feature = Fatty Streak – elevated lesions in the intima that contain accumulations of intracellular and extracellular lipid. Macrophages filled with lipid (foam cells) accumulate. Smooth m. cells also contain lipid.

Back 21

Atherosclerosis

Front 22

fibrillin disorder
faulty tunica media = vessels dissect
Mitral valve disorders = prolapse or redundant
Changes in chordae tendinae

Back 22

Marfan’s Syndrome

Front 23

could be caused by atherosclerosis – most commonly seen in abdominal aorta; could be a mycotic aneurysm; could be syphilitic aneurysm. In latter, the T. pallidum obliterates the vaso vasorum. Defined as a dilation of an artery with a diamter of at least 50% greater than the normal size of the artery.

A localized or diffuse dilation of an artery with a diameter at least
50% greater then the normal size of the artery; due to weakening of the vessel wall, followed
by dilation and a tendency to rupture; 2 causes are atherosclerosis and bacterial/fungal
infection; most common aneurysm in men > 55 is the abdominal aortic aneurysm.

Back 23

Vessel Aneurysms

Front 24

an intra vascular mass (clot) attached to vessel wall and is composed of varying proportions of coagulation factors, rbcs, and platelets. Can be caused by endothelial cell injury, especially arterial thrombi.

Back 24

Thrombosis

Front 25

A detached mass (clot, fat, gas) carried through the blood to distant site. These lodge in various places: atrium, microvasculature throughout body, pulmonary system

Back 25

Embolism

Front 26

The size of the lumen of the small muscular arteries and aretrioles is reduced, which leads to increased vascular resistance. Restriction in the luminal size may also result from active contraction of the smooth muscle in the vessel wall. Multiplication of smooth m. occurs and tunica media increases in thickness, smooth m. cells accumulate lipid; intimal thickness occurs in fat-free diet; cardiac m. cells increase in size and number (hyperplasia).

Back 26

Hypertension

Front 27

the characteristic acute myocardial rheumatic lesion. The body has a central region of degenerated collagen, surrounded by lymphocytes, plasma cells, some neutrophils, and histiocytes. The Anitschkow cell is the characteristic cell, recognized by its ribbon-like nucleus and eosinophilic cytoplasm; also called a cardiac histiocyte.

Found in connective tissue of myocardium, also in endocardium

Back 27

Aschoff Body

Front 28

reversible ischemia of peripheral arterioles usually involving
fingers and toes; it is a vasospasm involving arterioles; it is associated with another illness or secondary to another disease and the most common is an autoimmune disease.

Back 28

Raynaud’s phenomenon

Front 29

can be caused by a defect/damage to lymphatic vessels; especially significant it happens to larger lymphatic vessels; How fast can chyle accumulate in the thorax or pleural cavity with damage to the thoracic duct in the thorax?

Back 29

Lymphedema

Front 30

affects medium and large-sized arteries; vessels with an internal elastic lamina have a high degree of susceptibility; extracranial vertebral aa, superficial temporal arteries, ophthalmic aa are commonly affected; IEM fragments as neutrophils accumulate. Mononuclear giant cells are part of infiltrate.

Back 30

Giant Cell Arteritis

Front 31

1. Open sores on lining of stomach, small intestine and/or esophagus; can result in internal bleeding and if penetrates organ wall peritonitis; scar tissue
2. Burning pain from breastbone to navel; worse when stomach is empty; improves with food that buffers stomach contents
3. Majority due to bacterial infection (H. pylori, ...); medication (NSAIDS);
a. 1/5 people under age of 30 infected;  ½ over age of 60 infected
b. Smoking, stress, and spicy foods can aggravate but not cause
4. Treatment: appropriate antibiotics or antifungals; proton-pump inhibitors; antacids

Back 31

Peptic Ulcer

Front 32

1. Disruption of formation of RBC in bone marrow due to deficiency in vitamin B12
2. Can be caused by autoimmune gastritis  antibodies against the H+/K+ATPase   HCl in gastric juice (achlorhydria) and lack of synthesis of intrinsic factor

Back 32

Pernicious anemia:

Front 33

1. Gastrin-secreting tumors (aka gastrinomas) of pancreas
2. Hyperplasia and hypertrophy of fundic region
3. High acid secretion independent of food ingestion
4. Complications include: fulminant (sudden onset) stomach ulceration, diarrhea (gastrin causes inhibition of water and electrolyte absorption in intestine), steatorrhea (inability to absorb fat due to inactivation of pancreatic lipase by low pH), and hypokalemia (lower than normal level of K in blood)
5. H+ secretion continues regardless of [H+] of stomach since pancreatic gastrin not regulated by negative feedback

Back 33

Zollinger-Ellison syndrome:

Front 34

1. Due to extensive gastroesophageal reflux - symptoms include heartburn, indigestion, or gas; burning sensation below & behind the breastbone (sternum); treatment – antiacids & acid-blocking drugs
2. Barrett’s esophagus due to a change in epithelium of esophagus (stratified squamous  simple columnar) – this change is not accompanied by new symptoms
3. Patients at high risk for esophageal adenocarcinomas (risk is 30 – 125X higher); usually found late and thus not curable

Back 34

Gastric reflux (Barrett’s Esophagus)

Front 35

1 Results from destructive effects of certain glutens (esp. rye & wheat) on intestinal villi
2. Reduces surface area available for absorption
3. Treated by eliminating wheat and rye products from diet

Back 35

Gluten enteropathy:

Front 36

1. Includes: ulcerative colitis & Crohn’s disease
2. Clinically characterized by diarrhea, pain, and periodic relapses
3. Ulcerative colitis can affect musocsa of LARGE intestine
4. Crohn’s disease affects ANY segment of intestinal tract (small & large)
5. Crohn’s disesase is chronic inflammatory process, with immune system cells (lymphocytes, neutrophils, and macrophages) producing cytokines damaging intestinal mucosa, progressing into submucosa and muscularis externa; presence of granulomas (lymphocyte aggregates) typical feature; complications include: occlusion of intestinal lumen by fibrosis, formation of fistulas & intestinal performation

Back 36

Inflammatory Bowel Disease

Front 37

1. Caused by mutation in 1 – 4 genes preventing migration & differentiation of neural crest cells into neurons of ENTERIC nervous system. Neural crest cells fail to migrate to the colon; seen in down's
2. AKA aganglionosis
3. Aganglionic segment is permanently contracted & therefore does not allow entry of contents resulting in abnormal form of constipation
4. Seen shortly after birth → infant abdomen becomes distended and little meconium is eliminated
5. Biopsy of mucosa and submucosa confirms diagnosis → thick and irregular nerve bundles and lack of ganglion cells
6. Treatment: surgical removal of affected region of colon

Back 37

Hirschsprung’s disease (congenital megacolon):

Front 38

1. Second highest cause of cancer death in US (3rd most frequent in men; 2nd in women); 140,000 cases diagnosed in US yearly; usually 55 or older affected
2. Usually arises from adenomatous polps; may be asymptomatic for years; rectal bleeding frequently present
3. Probably diet-related (high-fat, refined carbohydrates and low in fiber)
4. Treatment: surgery with or without chemo and radiation therapy

Back 38

Colorectal carcinoma

Front 39

1. herniation of muscle wall of colon; mucosa and/or submucosal layers protrude thru weak sites in muscle wall
2. inflammation at site of diverticulosis
3. Affects 10% of US population > 40 years of age; by 60 and over ~ 50% of US population affected
4. Symptoms: abdominal pain and tenderness in left lower side of abdomen; cramping, nausea, vomiting, fever, chills, change in bowel habits; complications include bleeding, infections, perforations, blockage of colon
5. Dominant theory of cause – consumption of low-fiber diet
6. Treatment – increase fiber in diet

Back 39

Diverticulosis/Diverticulitis

Front 40

1. Inflammation of appendix due to blockage or previous infection
2. Symptoms: abdominal pain that originates in navel and shifts to lower right abdomen; pain increases over 12 – 18 hours becoming severe
3. Complications – rupture of appendix leading to abscess and/or peritonitis
4. Treatment – surgical removal

Back 40

Appendicitis

Front 41

See Box 16.4,
80% of tumors are benign, most orginate in parotid; most are pleomorphic containing ducts, CT elements (ground substance and collagen), and myoepithelial cells; most common treatment is surgical removal.

Back 41

Salivary Gland Tumors

Front 42

– major symptoms are xerostomia (ZEER-oh-STOH-mee-ah) and dry, gritty eyes; component of systemic disease, second most common autoimmune disease, female dominant

Back 42

Sjögren (pronounced "show-grins") -- Syndrome

Front 43

an inflammatory condition of the exocrine pancreas that results from injury to acinar cells. Acinar cell injury and duct obstruction are the major initiators. Some causes: (1) secretion against obstruction (gallstone); (2) inappropriate activation of proenzymes; (3) AIDS; (4) ethanol. Most common causes are alcohol abuse and bile duct obstruction.

Back 43

Acute pancreatitis

Front 44

80% of patients have visible secretory abnormalities of the pancreas; this disease causes mucous inspissation (′inspi′sāshən) in ducts and secondary atrophy of exocrine glands, atrophy of glands due to blocking lumens.

Back 44

Cystic Fibrosis (CF)

Front 45

Hepatocytes in Zone 3 undergo ischemic necrosis because they are the last to receive blood, in for example, congestive heart failure when they do not receive proper oxygen (hypoperfusion and hypoxia. No changes of cells in Zones 1 and 2

Back 45

Centrilobular Necrosis

centrilobular necrosis caused hypoxia referred to as cardiac cirrhosis

Front 46

a) swollen (balloon cells) hepatocytes in centrilobular region,

b) Mallory bodies in hepatocytes,
c) neutrophils present,
d) collagen deposited (fibrosis) around central vein,
e) some hepatocytes become fat cells.

Back 46

Alcoholic hepatitis

Front 47

death of hepatocytes leading to scarring or increased production of collagen destroying normal architecture.

Back 47

Cirrhosis

Front 48

gallstone impacted in cystic duct leading to: a) thickened muscular layer due to trying to overcome pressure,
b) impaired breakdown of fat,
c) high pressure in gall bladder rearranges mucosa.

Back 48

Cholecystitis

Front 49

hepatic stellate change function/type to lay down matrix and affect sinusoids (see “Hepatic Sinusoids” in handout.

Back 49

Role of hepatic stellate cells in portal hypertension

Front 50

substance is produced in the liver and one of its functions is to protect the lung from neutrophil elastase activity (review lung 10 in 10); 50% of patients will develop liver cirrhosis. The substance accumulates in the liver in PAS positive globules. Treatment for this deficiency is pooled substance given intravenously and liver and lung transplantation.

Back 50

α-1 Anti-trypsin (AAT) deficiency

Front 51

Thromboplastin

vW factor

Back 51

endothelial cell secretion

prothrombic agent

Front 52

Thrombomodulin

Back 52

anticoagulant

Front 53

Prostacyclin

Back 53

antithrombogenic agent

Front 54

ACE
Endothelin

Back 54

Vasoconstrictors

Front 55

EDRF
NO
Prostacylin
Bradykinin

Back 55

Vasodialators

Front 56

PDGF
Hemopoietic
CSF

Back 56

growth stimulants

Front 57

TGF

Back 57

growth inhibiting factors

Front 58

LDL
Cholesterol
VLDL

Back 58

produce free radicals

Front 59

Selectins

Back 59

adherence molecules