1
Q
What is myeloid tissue?
A
Hematopoietic tissue including
- Blood cell precursors located in the bone marrow
- Blood cells (erythrocytes, platelets, granulocytes, monocytes) located in the blood
2
Q
What is lymphoid tissue?
A
Tissue located in the lymphoid organs and can also be located in the blood (lymphocytes)
e.g. thymus, lymph nodes, spleen, MALT
3
Q
What is hematopoiesis
A
the process by which all of your blood cells are formed, develop and mature into their final adult types.
– myeloid cells produced from multipotential cells in bone marrow
– 4 cell lines, each line undergoes differentiation into committed cells
•erythroid/megakaryocytic
•macrophage/granulocytic
• eosinophilic
• mast cell/basophilic
4
Q
What is lymphopoiesis?
A
generation of lymphocytes - happens in lymphoid tissue
5
Q
Plasma vs. Serum
A
- plasma is the fluid component of blood (need to anticoagulate)
- serum is the fluid remaining if blood is allowed to clot
6
Q
What is CBC?
A
Complete blood test - used to evaluate features of blood
number of each blood cell type
7
Q
What is a differential test?
A
- Differential refers to the different types of wbc present
8
Q
What is a blood smear?
A
- done to assess the morphology (shape) of blood cells
- can often be used as a diagnosis
9
Q
What is anemia?
A
Anemia is a decrease in the red blood cell mass (and
therefore Hb) present in blood;
signs and symptoms are due to decreased ability of blood to carry oxygen
10
Q
How is anemia diagnosed?
How is the diagnosis different in men and women?
A
Usually assessed by looking at the Hb level
– anemia in male is defined as Hb <130
– anemia in female is defined as Hb < 115
11
Q
How are anemias classified?
A
– morphology
- etiology
12
Q
What are the 3 major groups of anemias based on morphology ?
A
- hypochromic microcytic (the presence of small, often less coloured, red blood cells in a peripheral blood smear)
- normochromic normocytic
Red blood cells appear to be normal, just fewer - macrocytic (A macrocytic class of anemia is an anemia (defined as blood with an insufficient concentration of hemoglobin) in which the red blood cells (erythrocytes) are larger than their normal volume.)
13
Q
What are the mechanisms of anemia?
A
- Loss of blood (chronic and acute)
- Destruction of red cells (hemolytic anemias)
- Decreased red blood cell production
14
Q
What are the inherited destructive abnormal anemias?
A
- abnormal membrane [Hereditary spherocytosis]
- abnormal enzymes [G6PD deficiency]
- abnormal Hb [Hemoglobinopathies]
15
Q
What is the acquired destructive abnormal anemias?
A
abnormal membrane [Paroxysmal nocturnal Hburia]
premature death and impaired production of blood cells
16
Q
What are the usual causes of destruction of normal RBC?
A
• immune, mechanical, infections (malaria), chemical
17
Q
What are the pathogeneses and names of decreased red blood cell production anemias?
A
– bone marrow failure [aplastic anemia, infiltration of bone marrow]
– defective DNA synthesis [megaloblastic anemias]
– defective HB synthesis [iron deficiency anemia]
18
Q
What are the signs and symptoms of anemia?
A
– pale skin and mucosa (conjunctiva) – fatigue, dyspnea on exertion – brittle nails – koilonychia (spoon shaped nails) – headache, decreased vision, drowsiness
19
Q
What are the causes of iron deficiency anemia?
A
- decreased intake
- decreased absorption
- increased loss
- increased requirements
20
Q
What is aplastic anemia?
A
Anemia characterized by loss of multipotent myeloid stem cells in the bone marrow with resulting pancytopenia
– decreased production of all three cellular components of the blood (red cells, platelets, and granulocytes)
21
Q
What are the causes of aplastic anemia?
A
– primary (Idiopathic)
– secondary
• cytotoxic drugs, radiation, viral infection
22
Q
How do you diagnose aplastic anemia?
A
– pancytopenia (CBC)
– bone marrow showing few blood-forming cells
23
Q
What are the clinical signs of aplastic anemia?
A
- ↓ wbc results in infections
- ↓ platelets results in bleeding
- ↓ Hb results in anemia
24
Q
What is megaloblastic anemia?
A
Anemias characterized by abnormal blood cell precursors
(megaloblasts) in the bone marrow and their descendants
in blood
25
What are the two major causes of megaloblastic anemias?
B12 deficiency and folate deficiency
– defective nuclear maturation due to impaired DNA synthesis
– causes production of abnormal cells
– abnormal cells are destroyed resulting in anemia
26
How do you diagnose megaloblastic anemias?
- peripheral blood (hypersegmented PMN, macrocytosis)
- bone marrow biopsy and aspiration (hypercellular and
megaloblasts)
27
What is Vitamins B12 and how does a deficiency occur?
– B12 is an essential nutrient because not able to make in body
– B12 is important because required for DNA synthesis
– Absorption of B12 requires intrinsic factor (made in stomach)
– impaired absorption
– decreased intake
– increased requirement
28
What is pernicious anemia?
- megaloblastic anemia due to lack of intrinsic factor with resulting
vitamin B12 deficiency
- lack of intrisic factor is due to autoimmune destruction of parietal
cells in stomach
29
What is the role of folate and what are the causes of deficiency?
- important because cofactor in DNA synthesis
```
– causes of folate deficiency
• decreased intake
• impaired absorption
• increased loss
• increased requirements
```
30
What are hemolytic anemias?
Hemolysis is the destruction of red cells
31
What are the causes of hemolysis?
– intracorpuscular defect (problem with rbc itself)
| – extracorpuscular defect (problem with body)
32
What are the extracorpuscular defects involved in hemolytic anemias?
- autoimmune destruction
- mechanical destruction
- infection
33
What are the intracorpuscular defects involved in hemolytic anemias?
- membrane defect [hereditary spherocytosis]
- Hb defect [sickle cell anemia]
- enzyme defect [G6PD defect]
34
What is sickle cell anemia?
• Inherited disorder of Hb due to a defect in β globin gene
– defective gene substitutes neutral aa for an acidic aa [HbS (α2S2)]
– in low oxygen, abnormal Hb polymerizes making red cells sickle
– results in chronic hemolytic anemia and small vessel occlusion
35
What is sickle disease vs. sickle trait?
Sickle disease
– homozygote for defective gene (>80% HbS)
– sickle cells in blood and sickling crises
Sickle Trait
– heterozygote for defective gene (<40% HbS)
– asymptomatic
36
What are Thalassemias?
Group of disorders caused by defect in genes coding for
| Hb chains resulting in decreased synthesis of normal Hb
37
How are Thalassemias classified?
on basis of type of chain affected
– β Thalassemia [defective synthesis of β chain]
– α Thalassemia [defective synthesis of α chain]
38
How do Thalassemias present clinically?
- depends on number of genes affected and nature of defective gene
– anemia is a hypochromic microcytic anemia
– in severe disease get iron overload
39
What are the different types of α thalassemias?
– silent carrier state (single gene deletion, asymptomatic)
– α thalassemia trait (2 gene deletion, mild anemia)
– hemoglobin H (HbH) moderate severe anemia)
• HbH is tetramer of β globins, doesn’t carry oxygen
– hydrops fetalis (4 gene deletion, intra-uterine death)
40
How do β thalassemias present?
– thalassemia minor (mild disease, asymptomatic)
– thalassemia intermedia (moderate severe anemia, no transfusion required)
– thalassemia major (severe disease, requires transfusions)
41
What is hereditary spherocytosis?
Group of disorders characterized by inherited defect of structural proteins in red cell
– defective red cells unable to maintain shape and form spherocytes
– the defective red cells are removed prematurely by the spleen
42
How are most hereditary spherocytosis inherited?
autosomal dominant inheritance
43
How does the severity of spherocytosis vary and present?
– chronic anemia of mild to moderate severity
– spherocytes present in blood
– hemolytic crises
– mild jaundice, splenomegaly
44
What are immune hemolytic anemias?
Group of anemias resulting from destruction of red cells by
antibodies
Incompatible blood transfusion (previously discussed)
• Hemolytic Disease of the Newborn (previously discussed)
45
What is autoimmune hemolytic anemia?
– body identifies antigen on own rbc as foreign, makes antibody
– Ag-AB complexes form, complement activation, rbc destruction
46
What are the causes of autoimmune hemolytic anemia?
• idiopathic
• secondary
– lymphoproliferative disease
– drugs
47
What is polycythemia?
An increase in number of red cells (and Hb)
48
What are the causes of polycythemia?
– primary
– secondary
• living at high altitude
• chronic lung disease
49
What is polycythemia rubra vera?
– neoplastic disease of red cell precursors in the bone marrow
– increased viscosity of blood
– insensitive to erythropoeitin
– require blood to be removed
50
What are leukopenia?
Abnormal decrease in number of white blood cells
51
What are the 2 types of leukopenia?
Neutropenia and lymphopenia
52
What is • neutropenia?
– decreased number of neutrophils
| – susceptible to bacterial infections
53
What are the causes of neutropenia?
* drugs
* chemicals
* radiation
* aplastic anemia
54
What is lymphopenia?
– decreased number of lymphocytes
55
What is leukocytosis?
Abnormal increase in number of white blood cells
56
What is neutrophilic leukocytosis?
(increased numbers of neutrophils)
– bacterial infections
– toxic changes, shift to the left
57
What is eosinophilia?
(increased number of eosinophils)
| – parasites, allergies, drug reactions
58
What is lymphocytosis?
(increased number of lymphocytes)
– viral infections
– chronic infections
59
What are leukemias?
– malignant diseases of leukocytes
– malignant proliferation of blood cell precursors in the bone marrow
malignant cells also enter peripheral blood
60
What are lymphomas?
– malignant diseases of lymphocytes
– malignant proliferation of cells in lymphoid tissue (usually lymph nodes)
– Hodgkin’s vs. Non Hodgkin’s Lymphoma
61
What is Hodgkin's lymphoma vs. non-Hodgkin's lymphoma?
Hodgkin's disease (lymphoma) = a form of malignant disease that is pathologically distinct from other lymphomas; Diagnosis = binucleated and multinucleated cells;
– group of lymphomas characterized by presence of Reed Sternberg cell (binucleated and multinucleated cells)
– bimodal age distribution (25 yo, 55 yo)
– staging important re prognosis
– chemotherapy very effective
Non-hodgkin's lymphoma = OTHER LYMPHOMAS
– diverse group of diseases
– classification (based on histological features) of low, intermediate and
high grade
62
What are leukemias?
is a group of cancers that usually begin in the bone marrow and result in high numbers of abnormal white blood cells
63
What are the different types of leukemias?
```
– acute vs. chronic
– myeloid vs. lymphoid (depends on what type of cell is being affected)
– ALL
– AML
– CLL
– CML
```
64
What is ALL?
(leukemia)
– most common type in children (most common malignancy in child < 5 yo)
– treatment with chemotherapy (remission in most patients, cure in 50%)
– very treatable
65
What is AML?
```
(leukemia)
– most common acute leukemia in adults
– several categories (FAB Classification)
– treatment with bone marrow transplant
– classified by genetics
```
66
What is CML?
(leukemia)
– chronic phase, accelerated phase, blast crisis
– chronic phase, blast crisis
– characterized by Philadelphia chromosome (2 genes fused together)
– can progress to AML
67
What is CLL?
(leukemia)
– elderly, low grade with slow progression
– malignant lymphocytes in blood may be very high
– B cells are more likely to become malignant
68
What is the most common type of leukemia in children?
ALL
69
What is the most common accute type of leukemia in adults?
AML
70
What are patechei?
- small microbleeds in skin
71
What is lymphadenopathy?
Symptom of lymphoma; disease of the lymph nodes, in which they are abnormal in size, number, or consistency
72
What are the symptoms of lymphomas?
- lymphadenopathy
| - constitutional symptoms
73
What are constitutional symptoms?
- symptoms of lymphomas
| - weight loss, fever, fatigue, etc.
74
What is follicular lymphoma?
```
(Non-hodgkin's)
– most common
– low grade
– elderly
– the follicular structure of the lymph nodes is partially preserved and the tumor cells resemble mature lymphocytes or follicular center-activated lymphocytes
```
75
What are diffuse large b-cell lymphomas?
– complete effacement (elimination) of the normal lymph node architecture
– Instead of normal lymphocyte, tissue is infiltrated with large lymphoid cells that have irregular nuclear outlines and prominent nucleoli.
– several types (50% of lymphomas)
– intermediate or high grade
– poor prognosis (spread into the parenchyma of major organs is common)
76
What is Burkitt's lymphoma?
– highly malignant tumor composed of small B cells that divide rapidly
– children from Northern Africa
– Epstein–Barr virus (EBV) infection
– chemotherapy
77
What is multiple myeloma?
Malignant disease of plasma cells
- monoclonal population results in monoclonal spike on
serum protein electrophoresis
78
What are clinical feature of multiple myeloma and when does it usually appear?
– Bone lesions
– Kidney damage
– Middle age usually
79
How do you diagnose multiple myeloma?
– bone marrow biopsy
– x-ray
– Serum Protein Electrophoresis (SPE)
80
What is hemostasis?
- a process which causes bleeding to stop
| - Interaction of vessels, platelets, coagulation factors
81
What are the 3 types of bleeding disorders?
- Vascular
- Platelet
- Clotting Factor
82
What are vascular bleeding disorders?
– mechanical trauma (most common)
– vessel wall fragility (can cause spontaneous bleeding)
– immune damage
83
What are platelet disorders?
– qualitative (number of platelets)
• Congenital
• Acquired [Chronic renal failure, Aspirin]
– quantitative (abnormality in structure)
84
What are clotting factor deficiencies and how are they classified?
- deficiency in clotting factor that leads to bleeding disorder
– congenital
• Hemophilia A (Factor VIII)
• Hemophilia B (Factor IX)
– acquired
• decreased/ defective production [Liver disease, Vitamin K
deficiency]
– increased consumption [Disseminated Intravascular Coagulation - DIC]
(Consumption of coagulation factors occurs during the formation of thrombi of any type and is most prominent in DIC)
– anticoagulants
85
What clotting factor is associated with Hemophilia A?
Factor VIII
86
What clotting factor is associated with Hemophilia B?
Factor IX
87
What are streptococcus mutans and what do they promote?
Bacteria that cause caries
88
What are some complications associated with dental caries?
* pulpitis (inflammation of dental pulp tissue)
* apical abscess (most common form of dental abscess and is caused by infection of the root canal of the tooth)
* periapical granuloma (chronic inflammation located at the apex of a non vital tooth)
* radicular cyst (most frequent cystic lesion related to teeth and result from infection of the tooth)
89
What is periodontitis
– inflammation of periodontal recesses (gingiva, periodontal membrane, alveolar bone)
90
What is the most common cause of tooth loss
periodontitis
91
What is stomatitis?
– inflammation of the mouth (oral mucosa)
92
What causes stomatitis?
– infectious causes
• viruses [herpes], bacteria, fungi [candida]
– non infectious causes
• aphthous ulcers (a recurrent round or oval sore or ulcer inside the mouth)
• immunologic
93
What is leukoplakia?
clinical term for a persistent white lesion
94
What is erythroplakia?
clinical term for a persistent red lesion
95
What is the most common type of malignant oral neoplasm?
squamous cell carcinomas (>95%)
96
What are some risk factors for malignant oral neoplasm?
tobacco, alcohol
97
How do malignant oral neoplasms present?
– may present as leukoplakia
– most common locations are anterior 2/3 of tongue, lower lip
– metastasize to regional lymph nodes
98
What is the treatment and survival rate for malignant oral neoplasms?
treatment with surgery and radiation (5 yr survival = 45%)
99
What is sialadenitis?
– inflammation of a salivary gland, usually the parotid gland
100
What causes sialadenitis?
– infectious causes
• viral [mumps]; bacterial [Staphylococcus aureus]
– autoimmune causes
• Sjogren’s syndrome is immune mediated inflammation of salivary + lacrimal glands
101
What is pleomorphic adenoma?
* benign salivary neoplasm of both epithelial and stromal elements
* most common salivary gland tumor
* needs proper excision, may recur locally
102
What is esophagitis?
inflammation of the epithelial lining of the esophagus
103
What are the causes of esophagitis?
– infectious causes [viral (Herpes), fungal (Candida)]
| – chemical causes [Gastroesophageal disease (GERD)]
104
What is Gastroesophageal disease (GERD)?
– reflux of gastric contents into esophagus resulting in inflammation
– relaxed tone of lower esophageal sphincter allows reflux of acid
105
What is Barrett's esophagus?
- symptom of GERD
• presence of metaplastic intestinal type epithelium in lower esophagus
• increased risk of developing adenocarcinoma of the esophagus
106
What is hiatus hernia?
– displacement of portion of the stomach above the diaphragm
107
What's the difference between a sliding hiatus hernia and a paraesophageal hiatus hernia?
* sliding hernia (90%) refers to “sliding” of stomach upwards
* paraesophageal hernia (10%) refers to portion of stomach protruding upward beside esophagus
108
What is achalasia?
– disorder of esophagus resulting in increased resting tone of LES (lower esophageal sphincter)
– food is unable to enter stomach due to increased tone of LES
109
What is esophageal varices?
– dilation of submucosal veins of the distal esophagus
110
What causes esophageal varices?
– often due to portal hypertension secondary to hepatic cirrhosis
– significant morbidity and mortality associated with rupture
111
What are the most common malignant esophageal neoplasms; where do they typically occur?
– usually carcinomas
• either squamous cell carcinoma or adenocarcinoma
– typically occur in lower portion of esophagus
112
What are some risk factors for malignant esophageal neoplasms?
– risk factors for squamous carcinoma include tobacco, alcohol
– risk factors for adenocarcinoma include Barrett’s esophagus
113
How do malignant esophageal neoplasms usually present?
– presents as ulceration or a mass
| – lymphatic invasion
114
What is gastritis?
– inflammation of the mucosal lining of the stomach
115
What causes acute gastritis compared to chronic gastritis?
– Acute gastritis
• acute erosive inflammation of the mucosal lining of the stomach
– stress, drugs (aspirin), alcohol
– Chronic gastritis
• chronic inflammation of the mucosa with acute exacerbations
• Helicobacter pylori infection
– H pylori is a bacteria that survives in the acidic gastric environment
– associated with one type of chronic gastritis
– chronic H. Pylori infection associated with increased incidence of gastric adenocarcinomas and lymphomas
116
What is autoimmune gastritis?
Chronic gastritis
• autoimmune destruction of parietal cells in the stomach (that secrete HCl)
• associated with increased risk of gastric adenocarcinoma
117
What is peptic ulcer disease?
– chronic multifactorial disease characterized by mucosal ulceration that extends through the entire gastric epithelial layer and into the muscularis
– localized chronic ulceration of gastric or duodenal mucosa
118
What causes peptic ulcer disease and what factors are associated?
– due to action of acid on weakened gastric or duodenal mucosa
– factors include H. pylori, stress, hormones
119
What are some complications associated with peptic ulcer disease?
– complications
• hemorrhage [melena, iron deficiency anemia, hematemesis]
• perforation [extend through the intestinal wall and form a hole; peritonitis]
• scarring [stenosis (narrowing), obstruction]
120
What is the most important neoplasm of the stomach?
carcinoma of the stomach (gastric carcinoma)
121
What are some risk factors for gastric carcinoma?
• risk factors include nitrosamines, Japanese, H. pylori
122
How do you classify gastric carcinomas?
All are adenocarcinomas
– on basis of gross appearance (polypoid, fungating, ulcerating, diffuse)
– on basis of histological appearance (intestinal type, signet cell)
123
What is the prognosis for gastric carcinoma?
[5 year survival 20%]
124
What is a Virchow node?
lymphatic spread of a gastric carcinoma
125
What is MALToma?
a low grade lymphoma arising in chronic H. pylori
| located in the MALT of the gastric lining
126
What is the most common site of gastrointestinal lymphomas?
the stomach
127
What is Meckel’s diverticulum?
– developmental disorder of small bowel due to persistence of the omphalomesenteric (vitelline) duct (Connection of the yolk sac to the embryonic digestive system)
128
How common is Meckel’s diverticulum?
– 2 % of population, 2 ft. from ileocecal valve, 2% ectopic gastric mucosa, 2 % develop symptoms
129
What are some causes of malabsorption in the small bowel?
• maldigestion, decreased absorption, impaired transport
130
What is an example of a malabsorption disease?
Celiac disease
131
What is celiac disease?
* damage to small bowel mucosa due to hypersensitivity reaction to gluten, a protein present in wheat
* malabsorption results from the damage to the small bowel mucosa
132
What is Girardia and what does it cause?
• Parasite
• Infections of the small bowel (beaver fever)
- It presents as diarrhea or malabsorption secondary to heavy colonization of the duodenum and the proximal small bowel.
133
How common are neoplasms of the small bowel?
Rare
134
What are 2 examples of malignant neoplasms in the small bowel?
• carcinoids
– term for low grade malignant neoplasm of neuroendocrine cells
– typically located in the submucosa, where they form small nodules elevating the overlying mucosa
– may produce carcinoid syndrome (diarrhea, flushing, bronchospasm)
– locally invasive
• lymphomas
135
What are 2 major inflammatory bowel diseases?
- Crohn's disease
| - ulcerative colitis
136
What is Crohn's disease?
- a chronic inflammation of the gastrointestinal tract that most often involves the terminal ileum and the colon
137
How does Crohn's disease present?
- skip lesions (a wound or inflammation that is clearly patchy, "skipping" areas that thereby are unharmed)
- transmural inflammation (inflammation does not remain limited to the mucosa but extends through the entire wall of the intestine
- granulomas (typically produced in response to infection, inflammation, or the presence of a foreign substance)
138
Where does Crohn's disease affect?
– may affect any part of the gastrointestinal tract (mouth to anus)
139
What are some complications associated with Crohn's disease?
• fissures (a tear in the lining)
• strictures (narrowing of a section)
• fistulas (abnormal connection or passageway that connects two organs or vessels that do not usually connect),
• adhesions (bands of fibrous tissue that can form between abdominal tissues and organs)
• dysplasia less common than ulcerative carcinoma
• extra-colonic manifestations
– arthritis, eye involvement, primary sclerosing cholangitis (inflammation and scarring of the bile ducts), skin lesions
140
What is ulcerative colitis?
an intestinal inflammation of unknown etiology that most often involves the large intestine (always includes rectum)
141
How are ulcerative colitis and Crohn's disease different?
- Crohn’s disease of the colon, which is typically segmental, ulcerative colitis is a diffuse disease
- UC doesn't extend to ileum
142
How does ulcerative colitis present?
- confluent (diffuse) involvement from rectum proximal to cecum
- small bowel is not involved
- inflammation is confined to mucosa
143
What are some complications of ulcerative colitis?
• toxic megacolon (acute toxic colitis with dilatation of the colon)
• dysplasia (abnormal growth)
• extra-colonic manifestations
– arthritis, eye involvement, primary sclerosing cholangitis, skin lesions (similar to Crohn's)
144
What is Hirschprung’s disease?
large bowel pathology
– congenital absence of colonic nerve ganglia resulting in portion of colon with no peristalsis
– dilation of colon proximal to aganglionic (no ganglia) segment
145
What is diverticular disease?
– disease, generally of the elderly, characterized by outpouchings (bulging) of colonic mucosa (pseudodiverticulum - False diverticula that do not involve muscular layers or adventitia)
- also includes diverticulosis and diverticulitis
146
What is diverticulosis vs diverticulitis?
Diverticulosis - disease characterized by the formation of diverticula (i.e., outpouchings of the intestinal wall). These diverticula may be solitary or multiple, congenital or acquired
Diverticulitis - term for inflammation of a diverticulum
147
What are some complications associated with diverticular disease?
* pericolonic (around or encircling the colon) abscess
* peritonitis (inflammation of the peritoneum)
* colonic stenosis (is a condition in which a part of the colon is very narrow, resulting in a partial blockage)
148
What is an example of infectious inflammation of the large bowel?
pseudomembranous colitis
149
What is pseudomembranous colitis?
– acute colitis (swelling of the colon) characterized by formation of a pseudomembrane
– due to toxin produced by bacterium Clostridium difficile
– due to broad spectrum antibiotic use
150
What is ischemic bowel disease?
-- includes several disorders that compromise blood flow through segments of the intestine
• certain parts of bowel susceptible to ischemia (watershed areas - regions of the body that receive dual blood supply from the most distal branches of two large arteries)
• ischemia (an inadequate blood supply) may result from atherosclerosis (disease in which plaque builds up inside your arteries)
- affects large bowel
151
What are hemorrhoids?
– variceal (varicose vein) dilation of veins in the submucosa of the anorectal area
152
What are hyperplastic polyps?
• most common colonic polyp (protruberant mass), no malignant potential
153
What are hamartomatous polyps?
- they are developmental abnormalities in which the normal components of the tissue aggregate in an abnormal manner
- occur in children
- commonly from Peutz-Jeghers syndrome
154
What is Peutz-Jeghers syndrome?
– autosomal dominant, characterized by multiple hamartomatous polyps and pigmented lesions on lips, peri-oral skin
– increased risk of malignancies
155
How is Peutz-Jeghers inherited?
autosomal dominant
156
What are adenomatous polyps?
* They are gland-like growths that develop on the mucous membrane that lines the large intestine
* adenomas
* benign neoplasms (tubular, villous, tubulovillous)
* increased risk of carcinoma if villous or high grade dysplasia
* familial adenomatous polyposis is autosomal dominant hereditary tumor syndrome
157
What is familial adenomatous polyposis?
autosomal dominant hereditary tumor syndrome in which adenomatous polyps are common
158
What is the prevalence of colonic carcinoma?
– 3rd most common malignant tumor in North America
| – 3rd most common cause of cancer-related death in North America
159
What ages are associated with colonic carcinoma??
– peak incidence in 60 - 80 years age group
| – rare before age 40 unless predisposing condition
160
What are some risk factor for colonic carcinoma?
- Inflammatory bowel disease (IBD)
| - Familial adenomatous polyposis (FAP)
161
How do the present and how can they be diagnosed?
– histologically adenocarcinomas
– metastasize via lymphatics or blood stream
– staging takes into account depth of penetration, nodes, mets
– majority occur in distal colon
– digital rectal exam as part of routine physical exam
162
What is appendicitis?
- something gets stuck in appendix = causes ->
– acute bacterial infection of appendix secondary to luminal obstruction (fecolith (extreme form of fecal impaction), lymphoid hyperplasia (increase in the number of lymphocytes),
pinworms)
163
How does appendicitis present?
– abdominal pain (McBurney’s point (over the right side of the abdomen), rebound tenderness), systemic features, leukocytosis (an increase in the number of white cells in the blood)
– rupture leads to peritonitis (inflammation of the peritoneum)
164
What is most common neoplasm of appendix?
Carcinoid
| adenocarcinomas also occur
165
What is the function of the hepatobiliary system?
```
– detoxify metabolic waste products
– remove old red blood cells (with spleen)
– produce bile
– synthesize plasma proteins
– synthesize plasma lipoproteins
– detoxify drugs
```
166
Blood flow of hepatobiliary system
– portal vein, hepatic artery supply the sinusoids
– blood drains through sinusoids in lobule into central vein
– blood exits via hepatic vein into IVC
167
What is bilirubin?
```
– breakdown product of hemoglobin
– conjugated (solubilized) in liver
– excreted into bile
– bile excreted into bowel
– altered by bacteria present in bowel
```
168
What is urobilinogen?
– reabsorbed (yellow urine)
| altered by bacteria present in bowel
169
What is stercobilinogen?
– not reabsorbed (stool brown)
| altered by bacteria present in bowel
170
What is cirrhosis?
End stage liver disease characterized by fibrosis and regenerative nodules
171
What are the causes of cirrhosis?
– alcohol
– viral hepatitis (HBV&HCV)
– metabolic and hereditary (hemachromatosis - causes your body to absorb too much iron from the food you eat, Wilson’s disease - genetic disorder in which copper builds up in the body)
– drugs
– biliary cirrhosis (immune system attacks the liver causing slow, progressive damage to the bile ducts)
172
What are some complications that arise from cirrhosis?
Portal hypertension
• varices (extremely dilated veins),
• ascites (abnormal accumulation fluid in the abdominal (peritoneal) cavity),
• splenomegaly (abnormal enlargement of the spleen)
173
What does hepatitis mean?
Inflammation of the liver parenchyma
174
What are some non-infectious causes of hepatitis?
Metabolic disorders
– hemochromatosis
– Wilson’s disease
– Alpha 1 antitrypsin deficiency
Drug/toxin induced
– acetaminophen
– alcohol
175
What are one main infectious cause of hepatitis?
Viral hepatitis
176
How many types of hepatitis are there?
6 (A,B, C, D, E, G)
177
What is hemochromatosis?
• autosomal recessive disorder of iron metabolism resulting in increased deposition of iron in various organs including
liver, heart, pancreas
178
What is Wilson’s disease?
• autosomal recessive disorder of copper metabolism resulting in increased deposition of copper in various organs
including liver, brain, and eye
179
What is alpha 1 antitrypsin deficiency?
• autosomal recessive disorder resulting in decreased alpha 1 antitrypsin, may cause emphysema, cirrhosis
180
How does acetaminophen cause hepatitis?
dose related necrosis of liver cells
181
How does alcohol cause hepatitis?
• three pathologic changes linked to alcohol use
1)fatty liver (steatosis)
– all alcoholics show steatosis [fatty yellow liver]
2) alcoholic hepatitis
– acute inflammation with fibrosis
3) cirrhosis
182
What is hepatitis A, how is it transmitted?
* fecal oral transmission
* no chronic state
* rarely lethal
* vaccine available
183
What is hepatitis B, how is it transmitted?
* parenteral, perinatal, sexual transmission
* 5-10% progress to chronic hepatitis
* massive hepatic necrosis and death are uncommon
* increased incidence of hepatocellular carcinoma
* vaccine available
184
What is hepatitis C, how is it transmitted?
* parenteral, sexual transmission
* 50-70 % progress to chronic hepatitis
* increased incidence of hepatocellular carcinoma
* no vaccine
185
What is hepatitis D, how is it transmitted?
* parenteral, possibly sexual transmission
| * requires coinfection with hepatitis B
186
What is hepatitis E, how is it transmitted?
• fecal oral transmission
187
What is a hepatic abscess and how are they caused?
– abscesses may form in liver parenchyma
| – maybe caused by bacteria or by ameba (a parasite)
188
What is hydatid disease and how are they caused?
– a disease of various organs cause by a parasite [echinococcus (cestode (tapeworm))] characterized by
formation of cysts on liver
189
What is schistosomiasis?
– liver disease results from schistosome (a parasite) depositing eggs in branches of portal vein
190
What is ascariasis?
– liver disease resulting from obstruction of bile ducts by the parasite
191
What is primary sclerosing cholangitis?
Immune disorder
– disease of unknown etiology characterized by destruction of intra-hepatic and extra- hepatic bile ducts by
lymphocytes and macrophages
– blocked bile ducts
192
When does primary sclerosing cholangitis usually occur?
Younger males
most also have inflammatory bowel disease (Ulcerative Colitis > Crohn's Disease)
– increased incidence of cholangiocarcinoma (cancer that arises from the cells within the bile ducts)
193
What is auto-immune hepatitis?
– chronic hepatitis in young females characterized by presence of autoantibodies to specific antigens
– favorable response to steroids
– associated with other vautoimmune diseases
194
What is primary biliary cirrhosis?
– disease of unknown etiology characterized by destruction of small intra-hepatic bile ducts and eventual
cirrhosis
– possibly T-cell mediated
– autoimmune disease affecting middle age females
– antimitochondrial antibodies in 95%
– cirrhosis develops over 10-15 yrs.
– no cure
195
What are the common benign neoplasms of the liver and which is most common?
– cavernous hemangioma (most common)
| – hepatocellular adenoma
196
What is cavernous hemangioma?
* benign neoplasm of endothelial (blood vessel ) origin
| * most common benign neoplasm in
197
What is hepatocellular adenoma?
* benign neoplasm of hepatocyte origin
| * young females on oral contraceptive pill
198
What are the most common malignant neoplasms of the liver?
– hepatocellular carcinoma [HCC]
| – metastatic carcinoma
199
What is hepatocellular carcinoma (HCC)?
• malignant neoplasm of hepatocytes
• tumors may be diffuse, solitary, or multiple nodules
• AFP is a protein usually secreted by fetal hepatocytes
– AFP levels are elevated in HCC and useful as tumor marker
200
What are the risk factors for HCC?
• risk factors include cirrhosis, HepB Virus, HepC Virus, hemochromatosis (too much iron absorption), alpha 1 antitrypsin deficiency
201
What is the most common malignancy of the liver?
metastatic carcinoma
202
What is cystic duct?
from gallbladder empties into common hepatic duct forming common bile duct
203
What is cholelithiasis?
Presence of gallstones in the gall bladder
204
What are the different types of gall stones?
* cholesterol stones (10 %)
* pigment stones (15%)
* mixed stones (75%)
205
How do you diagnose gall stones?
diagnose by ultra-sound
206
What are complications of cholelithiasis?
* cholecystitis (inflammation of the gallbladder)
* obstructive jaundice (symptoms develop due to a narrowed or blocked bile duct or pancreatic duct, preventing the normal drainage of bile from the bloodstream into the intestines)
* ascending cholangitis (inflammation of the bile duct)
* gallstone ileus (small bowel obstruction caused by an impaction of a gallstone within the lumen of the small intestine)
207
What is cholecystitis?
inflammation of the gallbladder
– usually due to gallstones
– usually due to gallstones
– acalculous cholecystitis = no stone
208
What is choledocholithiasis?
stone present in the common bile duct
209
What are the neoplasms associated with the biliary tract?
– adenocarcinomas
– cholangiocarcinoma
• associated with Primary sclerosing cholangitis, clonorchiasis (infectious disease caused by the Chinese liver fluke)
210
What is pancreatitis?
– inflammation of the cells of the pancreas
211
What is acute pancreatitis?
– acute inflammation with tissue necrosis due to release of pancreatic enzymes
212
What are the main causes of acute pancreatitis?
alcohol and gallstones responsible for 80 % of cases
213
What are some complications that arise from acute pancreatitis?
* abscess
* pseudocyst (a fluid-filled cavity resembling a cyst but lacking a wall or lining)
* peritonitis (inflammation of the peritoneum)
* chronic pancreatitis
* diabetes
214
What is chronic pancreatitis and what is an important factor?
– persistence of inflammation after original inciting agent removed
mation after original inciting agent removed
– progressive fibrosis
– alcohol important factor
215
What is an example of an exocrine pancreas neoplasm?
– Malignant
• pancreatic carcinoma
– adenocarcinoma arising from duct epithelial cells
– poor prognosis
216
What type of epithelium lines the urinary tract?
Transitional type epithelium
217
What are the major renal syndromes?
* nephritic syndrome
* nephrotic syndrome
* asymptomatic hematuria, asymptomatic proteinuria
* acute renal failure
* chronic renal failure
* renal tubular defects
218
Oliguria
– decreased urine production
219
Anuria
– no urine production
220
Polyuria
| What is an example of when this happens?
– increased urine production
Diabetic - because increased osmotic pressure due to high blood glucose levels
- In kidney, gets filtered into urine - more pee
221
Hematuria
– passage of blood in urine
222
Proteinuria
– protein in urine
223
What is acute nephritic syndrome
```
- diagnosed on the basis of typical clinical and laboratory findings
– syndrome includes
• oliguria
• hematuria
• proteinuria
• edema
• hypertension
```
224
When does nephritic syndrome usually happen?
– typically occurs 2-3 wks after throat infection with Gp A strep
225
Nephritic vs. nephrotic
At the most basic level, remember that nephrotic syndrome involves the loss of a lot of protein, whereas nephritic syndrome involves the loss of a lot of blood.
- also, difference in cause:
Nephritic - strep
Nephrotic - glomerulonephritis and systemic diseases (diabetes mellitus, lupus)
226
What is nephrotic syndrome?
– syndrome characterized by loss of large amounts of protein in urine with resulting hypoalbuminemia and edema
227
What causes nephrotic syndrome?
– variety of causes including
• minimal change glomerulonephritis (inflammation of the glomeruli)
• membranous glomerulonephritis
• membranoproliferative glomerulonephritis
• focal segmental glomerulosclerosis
• systemic diseases (diabetes mellitus, lupus)
228
What are some complications associated with nephrotic syndrome?
– prone to infections and thrombi due to loss of proteins involved in immunity and coagulation
229
What is acute renal failure?
– your kidneys suddenly become unable to filter waste products from your blood
– acute onset of decreased urine production
– develops over days to weeks
– decreased renal function, oliguria, electroloyte disturbances
230
What is the prognosis for acute renal failure?
– usually reversible
| • if not reversible, require dialysis or transplant
231
What are the causes of acute renal failure and how are they divided?
– causes divided on basis of location of disorder
• prerenal
– eg. decreased renal perfusion due to congestive heart failure
• renal
– eg. glomerular disease such as acute glomerulonephritis
• postrenal
– eg. Ureteric obstruction due to stones
232
What is chronic liver failure?
– condition characterized by a gradual loss of kidney function over time
– insidious decrease in renal function due to damaged kidneys
233
What are the stages of chronic renal failure?
usually several stages as renal function decreases
• diminished renal reserve (kidney's ability to increase its basal glomerular filtration rate)
• renal insufficiency (poor function)
• renal failure
• end stage renal failure
– end stage kidney refers to common appearance of a terminally damaged kidney that may be due to a number of
causes
– require dialysis or transplant
234
What are the two classifications that you can divide glomerular diseases into?
Primary (of unknown cause) and secondary (from a different known cause or medical condition)
235
What are the main primary glomerular diseases?
– minimal change glomerulopathy
– primary membranous nephropathy
– acute post-streptococcal glomerulonephritis
236
What are the main secondary glomerular diseases?
– immunologic diseases (SLE)
| – metabolic disorders (diabetes mellitus)
237
What is primary membranous nephropathy?
| Is it responsive to corticosteroids?
– characterized by diffuse (membranous) thickening of glomerular basement membrane due to immune complex
deposition
– makes glomeruli leaky
– not responsive to corticosteroids
– progresses to end-stage renal failure over 10-15 years
238
What is the most common cause of nephrotic syndrome in adults?
primary membranous nephropathy
239
What is minimal change glomerulopathy (lipoid nephrosis)?
| Is it responsive to corticosteroids?
– glomerular disease of unknown origin
– minimal change because can't see change in light microscope
– (individual foot processes, that are essential for determining what gets filtered, on glomerulus can no longer be made out- it is like they have all just “melted” together into a single thin layer. This important barrier in the filtration process can no longer keep protein from being filtered out of the blood and into the urine)
– unknown etiology
– responsive to corticosteroids, may recur
240
What is the most common cause of nephrotic syndrome in children?
Minimal change glomerulopathy (lipoid nephrosis)
241
What is acute glomerulonephritis? When does it occur?
– immune mediated inflammation of the glomerulus
– follows Group A streptococcal infection in 90%of cases
– typically 1 to 4 weeks after a strep throat or skin infection
242
What does acute glomerulonephritis classically look like?
fever, nausea, oliguria, hematuria, mild proteinuria, peri-orbital edema
243
How does the prognosis change in children and adults?
– usually self limited in children
• 90% of children recover in 2 to 3 months with conservative therapy
• 5-8% of children have abnormal urinary findings for 6 to 8 months
– worse prognosis in adults
• 60% recover promptly
• >30% have prolonged abnormal renal function
244
How is diabetes mellitus related to glomerular diseases?
– disorder of the hormone insulin resulting in uncontrolled hyperglycemia
– diabetics develop kidney damage
• glomerulosclerosis (hardening of the glomeruli in the kidney)
• arteriosclerosis
• pyelonephritis (inflammation of the kidney)
• papillary necrosis (renal papillae die - where openings of the collecting ducts enter the kidney and where urine flows into the ureters)
– first indication of renal damage is appearance of albumin in urine
– progression can be slowed by controlling hyperglycemia and hypertension
245
What is adult polycystic kidney disease?
- congenital disorder
– progressive number of variable sized cysts with age
– kidneys are greatly enlarged
246
What is the most common inherited disease of the kidney?
Adult polycystic kidney disease
247
How is Adult polycystic kidney disease inherited?
autosomal dominant inheritance
248
What is Autosomal recessive polycystic kidney disease?
– large numbers of small cysts within kidney
| – fatal at young age (infant)
249
What is cystic renal dysplasia?
– congenital disorder of development of the kidney
| – usually unilateral, affects children
250
What is acute pyelonephritis?
Bacterial infection of the kidney
251
What are the routes of infection for acute pyelonephritis?
– ascend through the urinary tract (85%)
• gram negative bacteria (E. coli most common)
– via the blood stream
• gram positive bacteria
252
If there is a gram positive bacteria infection present in acute pyelonephritis, what was the likely route of infection?
via the blood stream
253
If there is a gram negative bacteria infection present in acute pyelonephritis, what was the likely route of infection?
ascend through the urinary tract
254
What are some predisposing factors to Acute pyelonephritis?
bladder obstruction, urinary stones, vesicoureteral reflux (urine flows retrograde, or backward, from the bladder),
pregnancy
255
What are the 4 main types of renal stones?
– calcium stones, struvite stones, uric acid stones, cystine stones
256
What are the most common types of renal stones?
Calcium containing stones are most common
257
How can struvite stones arise?
chronic urinary tract infection
258
What is Cystitis?
– inflammation of the bladder
259
What is Acute tubular necrosis?
- circulatory change
– sudden severe drop in bp causing death of renal tubular cells
– acute renal failure
– may resolve if able to restore adequate perfusion to kidney
260
What is Benign nephrosclerosis?
– ischemic damage to glomeruli with resulting loss of glomeruli
– progressive disease of the kidneys that results from sclerosis (hardening) of the small blood vessels in the kidney
261
How does hypertension affect renal tract?
– systemic hypertension results in fibrinoid necrosis ( form of cellular death that results in the formation of fibrous tissue) of vessel walls
– malignant hypertension refers to a relatively sudden and large increase in pressure
• causes characteristic damage to renal arterioles
262
What is renal cell carcinoma?
– malignant neoplasm of renal epithelial cells
263
What is the most common renal tumor?
Renal Cell Carcinoma
264
What is the etiology of renal cell carcinoma?
– most are sporadic (not inherited)
| • loss of one allele of a tumor suppressor gene in 98% of sporadic
265
What paraneoplastic syndrome (disorders triggered by an altered immune system response to a neoplasm) is caused by Renal Cell Carcinoma?
Hypercalcemia due to parathyroid hormone related peptide
- Among others
- these types of disorders are common in RCC
266
What is the survival rate of Renal Cell Carcinoma?
– 5 yr. survival 45 %
• early diagnosis confers better prognosis
• invasion of renal vein or perinephric fat confers worse prognosis
267
What is Wilm's tumor? When is it diagnosed? What is prognosis?
– malignant neoplasm of primitive renal tissue (blastema - mass of cells capable of growth and regeneration into organs or body parts)
– usually diagnosed between 2 and 5 years of age
– surgery combined with chemotherapy gives excellent results
268
What is the most common solid tumor of children?
Wilm's tumor
269
What is the etiology of Wilm's tumor?
– most are sporadic
270
What is renal Transitional cell carcinoma? prognosis?
– malignant neoplasm of transitional epithelial cells in renal pelvis
– usually low grade exophytic tumors
– prognosis depends worse for high grade tumors
271
What are Urinary bladder infections usually caused by? What are some less common causes?
- gram negative bacteria (E. coli, proteus)
- Schistosomiasis (a disease caused by parasitic flatworms called schistosomes) - common in Egypt
- Cytomegalovirus infection in immunocompromised individuals
272
What is urinary Transitional cell carcinoma?
– malignant neoplasm of transitional epithelium in the bladder
– often multifocal
273
How does urinary bladder Transitional cell carcinoma present?
hematuria, dysuria, pain
274
What are the 2 different types of urinary bladder Transitional cell carcinoma?
– papillary (finger-like) vs. sessile (flat) describe gross appearance
• exophytic (tending to grow outward) papillary tumor usually low grade, good prognosis
• sessile tumor usually high grade, worse prognosis
275
What is the most common risk factor for urinary bladder Transitional cell carcinoma? What are some others?
- Smoking
| - aniline dyes, Schistosomiasis
276
What is the treatment for urinary bladder Transitional cell carcinoma?
surgery
277
How is sperm produced?
– occurs within seminiferous tubules in the testes
– seminiferous tubules lined by germ cells
– sperm continually produced from germ cells
278
Where is testosterone produced in male repro system?
produced by Leydig cells in the testes
279
What is Cryptorchidism?
```
failure of the testicles to descend into the scrotum
– may be corrected surgically
– associated with
• 10X risk of malignant transformation
• infertility
```
280
What are Epididymoorchitis, urethritis?
– inflammation of the epididymis and testes and/or urethra
281
What are some causes of Epididymoorchitis, urethritis? Give examples of each
```
– Sexually transmitted diseases
• Gonorrhea, Chlamydia
– Uropathogens
• gram negative bacteria (E. coli)
– viruses
• mumps (1/3 of those with mumps develop orchitis - inflammation of the testicles)
```
282
What is Balanitis?
– inflammation of the glans penis (head of penis)
283
What is genital herpes? How does it present in males?
– Herpes simplex virus type 2
– vesicular eruptions, pain
– remains dormant in neural ganglion cells, may recur
284
What is gonorrhea? How do you cure it? What are some complications?
– Neisseria gonorrhoeae (bacteria)
– purulent urethritis (urethral inflammation and pus filled discharge)
– antibiotics to cure
– complications
• prostatitis (swelling and inflammation of the prostate gland), epididymitis (infertility if scarring)
• arthritis
285
What causes Non-specific urethritis with no purulent discharge?
Chlamydia, mycoplasma (types of bacteria)
286
What is Syphilis?
Treponema pallidum (spirochete bacteria)
287
What are the stages of syphilis?
```
• primary stage
– painless chancre (ulcer)
• secondary stage systemic spread if untreated
– fever, malaise, rash
• tertiary stage
– small vessel vasculitis
– cardiac and CNS complications
```
288
What are the most common testicular neoplasms?
Germ cell tumors (90%)
289
What are the different types of testicular germ cell tumours?
```
– seminoma
– non-seminoma
• embryonal
• teratocarcinoma
• choriocarcinoma
– mixed (seminoma and non-seminoma)
– teratoma (umor made up of several different types of tissue)
– yolk sac tumor (tumors composed of yolk sac components)
```
290
What is a seminoma (testicular germ cell tumour)?
If tumor cells retain the features of primitive gonocytes, forming a neoplasm composed of a single cell type -- tumor of seminal epithelium–like cells
291
What is an non-seminoma - embryonal testicular germ cell tumour?
if the tumor cells acquire the characteristics of embryonic cells from germ cell origin
292
What is an non-seminoma - teratocarcinoma testicular germ cell tumour?
malignant tumor that is composed of embryonal carcinoma cells and somatic tissues
293
What is an non-seminoma - choriocarcinoma testicular germ cell tumour?
Tumors composed of malignant trophoblastic (cells forming the outer layer of a blastocyst) cells
294
What are sex cord stromal tumors?
Hormonally active tumors
| - can be from Leydig (testosterone) or Sertoli (inhibin) cells
295
How can you determine presence of testicular neoplasm? Which type cannot be identified this way?
– different testicular neoplasms produce different substances (“tumour markers”) that can be measured in the
blood
– measurement of the levels of these various substances helps to identify the presence
- Seminomas - no serologic tumor markers
296
Are most Testicular neoplasms malignant or benign?
Malignant
297
What is prognosis of seminoma and non-seminomatous germ cell tumours? What's the difference in treatment?
Seminoma - 90% cure rate
| Non-semi - 85% have a 5 year survival - no radiation therapy
298
What is a Benign prostatic hyperplasia of the prostate?
– benign hyperplasia of prostate epithelium and stroma
299
When does a Benign prostatic hyperplasia of the prostate usually appear?
common in elderly males
300
What are the symptoms of Benign prostatic hyperplasia of the prostate?
– causes urgency, frequency, dribbling
| – increased incidence of bladder infections
301
What is Prostatic carcinoma?
malignant neoplasm of glandular epithelium in the prostate
| – most are adenocarcinomas (a malignant tumor formed from glandular structures in epithelial tissue)
302
When does Prostatic carcinoma of the prostate usually appear?
usually elderly males
303
What is the most common cancer in males?
Prostatic carcinoma
| – third most common cause of cancer-related deaths in males
304
Where are Prostatic carcinomas usually located?
posterior part of prostate
| • prostate can be palpated by digital rectal exam
305
What is a useful screen for an at risk population for Prostatic carcinomas?
Prostate Specific Antigen (PSA)
• prostate cells produce PSA, secrete into semen, small amount ends up in blood
• prostate cancer cells produce PSA, more ends up in blood
• useful to screen population at risk, other causes of increased PSA
306
How are Prostatic carcinomas treated?
– surgery +/- radiation, chemotherapy
| – prognosis depends on stage and grade
307
What are the histological components of the female reproductive system?
– stratified squamous mucosa (vulva, vagina, ectocervix)
– glandular epithelium (endocervix, endometrium, fallopian tube
– germ cells (ovary)
308
What is Hermaphroditism? Male vs. Female vs. True?
– discordance between genotypic and phenotypic sex
True hermaphroditism
• have both male and female gonads
Male pseudohermaphroditism
• genotypically male, phenotypically female
Female pseudohermaphroditism
• genotypically female, phenotypically male
309
How do common STIs usually present in females?
– present with vaginal discharge, lesions, pelvic pain, dyspareunia (difficult or painful sexual intercourse)
310
How does genital herpes present in females?
* vesicles on genitalia that coalesce and ulcerate
| * appear 3-7 days after exposure (only 30% develop lesions)
311
What how does HPV present?
* labial, vaginal and cervical warts (condyloma)
| * certain types associated with carcinoma (see below)
312
What is a condyloma acuminatum?
large vulvar wart
313
What types of cancer are conduloma acuminatum associated with?
HPV 6,11
314
How does Chlamydia present in females?
• present with urethritis or cervicitis with discharge, Pelvic Inflammatory Disease
315
How does gonorrhea present in females?
urethritis or cervicitis with discharge, Pelvic Inflammatory Disease
316
How does syphilis present in females?
• vulvar ulcers
317
What is bacterial vaginosis?
is a mild infection of the vagina caused by bacteria
318
What types of organisms are associated with bacterial vaginosis (BV)?
– Candida - fungal growth that is usually maintained by bacteria
– Trichomonas - common sexually transmitted disease, caused by infection with a protozoan parasite called Trichomonas vaginalis
– Gardnerella - bacteria that causes BV
319
What is pelvic inflammatory disease? symptoms?
– chronic, extensive infection of upper reproductive tract
| – salpingitis (inflammation of the fallopian tubes), tubo-ovarian abscess, peritonitis
320
What usually causes pelvic inflammatory disease?
usually secondary to STD (Neisseria, Chlamydia)
321
What are some complications associated with pelvic inflammatory disease?
* chronic non-specific infection [fever, malaise, fatigue]
* infertility secondary to scarring of fallopian tubes
* pelvic mass with pain
* spread of infection
322
What is endometrial hyperplasia?
– normal menstrual cycle requires normal functioning of the hypothalamic-pituitary-ovarian axis
– endometrial hyperplasia is thickening of the endometrial mucosa due to continued estrogen stimulation with inadequate progesterone
323
What is the main factor associated with endometrial hyperplasia?
anovulatory cycles (no ovulation therefore no progesterone secretion)
324
What causes anovulatory cycles?
• functional causes
– puberty, anxiety, athlete
• organic
– excess estrogen (Oral Contraceptive Pill, tumors)
325
What is simple vs. complex hyperplasia?
- simple is an innocuous change, whereas the other forms of hyperplasia should be considered as possible precursors of cancer
- simple = cystic, simple glands
- complex = more crowded glands
326
How does atypia affect complex hyperplasia?
• increased risk of endometrial adenocarcinoma
| - equivalent of dysplasia
327
What type of carcinoma is carcinoma of the vulva?
– squamous cell carcinoma
328
How is squamous cell carcinoma detected + treated?
– raised or ulcerated lesion
– pre-neoplastic change may present as white or red patch
– biopsy to assess
– surgical excision +/- adjuvant therapy
329
What type of carcinoma is carcinoma of the vagina?
– squamous cell carcinoma
| – clear cell carcinoma
330
When is clear cell carcinoma more common?
• women born to mothers on Diethylstilbestrol (DES) (synthetic form of the female hormone estrogen) during pregnancy
331
How is mortality of carcinoma of cervix reduced?
Pap test (early diagnosis)
332
What are some risk factors for carcinoma of cervix?
* sexual intercourse at early age, multiple partners, HPV infection (certain types), other venereal diseases
* environmental component and other factors
333
What type of carcinoma is carcinoma of the cervix?
– squamous cell carcinoma
334
How does cervical cancer usually present?
precursor lesion = dysplasia (Cervical intra-epithelial neoplasia)
• lack of normal maturation of squamous epithelium
• occurs at transition zone (the outer surface of the cervix (exocervix) is covered with squamous epithelium, whereas the endocervical canal is lined by columnar epithelium)
• graded mild, moderate, severe
• cells shed into vagina (Pap smear)
335
What types of HPV are associated with cervical cancer?
• HPV types 16, 18, 31, 33, 34, 35 associated
336
What are koilocytic changes in cervical cancer?
refers to characteristic changes due to HPV
| - squamous epithelial cell that has undergone a number of structural changes
337
What is a leiomyoma (fibroid) of the uterus? when does it arise? what are symptoms?
– benign neoplasm derived from smooth muscle in wall of uterus
– responsive to estrogen, arise during reproductive age
– usually asymptomatic
– may produce symptoms due to mass effects, bleeding
338
What is the most common uterine neoplasm?
Leiomyoma (fibroid)
339
What is a Leiomyosarcoma of the uterus? how common?
– malignant neoplasm derived from smooth muscle in wall of uterus
– very rare
340
What is Endometrial adenocarcinoma ?
– malignant neoplasm derived from epithelial cells in endometrium
341
What is the most common malignant tumour of female reproductive tract?
Endometrial adenocarcinoma
342
What age is Endometrial adenocarcinoma most common?
elderly
343
What are some risk factor associated with endometrial adenocarcinoma?
(related to increased estrogen (hyperestrinism))
• estrogen secreting tumor, exogenous estrogen
• obesity
• nulliparous or early menarche, late menopatuse
344
What is the most important prognostic feature of endometrial adenocarcinoma?
Stage - I-IV
| Grade is also important (low, int, high)
345
How do you diagnose endometrial adenocarcinoma?
endometrial biopsy, dilation and curettage ("scoop" of tissue)
346
What is therapy for endometrial adenocarcinoma?
hysterectomy +/- adjuvant therapy
347
What are ovarian cysts?
fluid filled cavities lined by epithelium
– usually small, solitary, asymptomatic
– if large, then further investigation to rule out neoplasm
348
How to ovarian cysts usually arise?
from unruptured follicles (follicular cysts)
| • may also represent cystic corpora lutea or inclusions of surface cells
349
What is polycystic ovary syndrome? How does it present, what does it cause?
– multiple cysts in both ovaries due to complex hormonal disturbances of the
hypothalamic-pituitary-ovarian-adrenal axis
– presents with menstrual irregularities
– cause of infertility
350
What is the second most common group of tumours of tumors of female repro system?
Ovarian neoplasms
351
What has the highest mortality of female reproductive tract tumors?
ovarian neoplams
352
What are the 3 major groups of neoplasms based on histogenics?
* surface epithelial tumors
* germ cell tumors
* sex cord stromal tumors
353
What are the risk factors for ovarian tumours?
not well defined
• ovarian dysgenesis (abnormal organ development during embryonic growth)
• BRCA1 and BRCA2 gene mutations
oral contraceptives not linked to ovarian neoplasms
354
What are the different types of ovarian neoplasms?
- Tumors of the surface (germinal) epithelium
- Tumors of the germ cells
- Tumors of the sex cord stromal cells
- Nonspecific tumors of the ovarian stroma or metastases
from other organs
355
What are the different types of surface epithelial tumors?
serous, mucinous, endometrioid, clear cell and transitional cell types
356
Which type of surface epithlial tumour is the most common?
Serous epithelial tumors
357
What type ovarian neoplams is the most common?
Surface epithelial tumors (70%)
358
What is a serous epithelial tumour? malignancy?
– typically cystic, filled with clear fluid
– can be benign, borderline malignant, and malignant tumors
– 25 % of benign tumors and 50 % of malignant tumors are bilateral
359
What is a mucinous epithelial tumour? malignancy?
– also typically cystic, filled with viscus fluid (looks like mucus)
– can be benign, borderline malignant, and malignant tumors
– 25 % of benign tumors and 50 % of malignant tumors are bilateral
360
What is an endometrioid epithelial tumour? malignancy?
resemble endometrial glands and do not secrete anything
– typically solid
– malignant
361
What are ovarian germ cell tumours? age? when do they occur?
originate from activated oocytes that have also undergone a neoplastic transformation
- young females
362
What is an ovarian teratoma? age and prevalence? malignancy?
– most common ovarian neoplasm in young females
– cystic, contain hair, sebaceous material (dermoid cysts)
– may contain teeth, bone cartilage
– benign
• may undergo malignant transformation (malignant teratoma)
363
What is an immature teratoma? malignancy?
– teratoma that contains immature neural tissue
| – may behave malignantly
364
What is an ovarian firbroma? Malignancy?
– benign neoplasm of fibroblasts
365
What is a thecoma? Malignancy?
– benign, solid and firm neoplasm of spindle cells (theca cells)
– produce estrogens
366
What is a granulosa cell tumour? Malignancy?
– neoplasm of granulosa cells (somatic cell of the sex cord that is closely associated with the developing female gamete)
– benign or malignant,may produce estrogen
367
What are 2 genital organ factors for fertility?
* PID (pelvic inflammation)
| * Asherman’s syndrome - acquired, gynecological disorder characterized by changes in the menstrual cycle
368
What are some diseases of pregnancy?
- Ectopic pregnancy
- Placenta accreta
- Placenta previa
- Toxemia of pregnancy
- Preeclampsia
- Eclampsia
369
What is an ectopic pregnancy?
– implantation of fertilized ovum outside the uterine cavity
– usually occurs in fallopian tube
– trophoblast cells of placenta invade wall of tube, begins enlarging
– may rupture
• surgical emergency
370
What is placenta accreta?
– abnormally deep penetration of placental villi into wall of uterus
- may cause extensive bleeding after birth
371
What is placenta previa?
– abnormal placental implantation site in lower uterine segment
- positioning of the placental disk over the internal orifice of the cervix
372
What is Toxemia of pregnancy?
– disease of pregnancy of unknown pathogenesis resulting in characteristic symptom complex in the mother
- includes preeclampsia and eclampsia, is a disease that occurs as a result of an abnormally functioning placenta or abnormal maternoplacental interaction.
373
Preeclampsia vs. eclampsia
Preeclampsia
– presents with hypertension, edema, and proteinuria
– occurs in third trimester
– may progress to eclampsia
Eclampsia
– hypertension, edema, proteinuria and seizures
– life threatening, must treat seizures, deliver baby
374
What is gestational trophoblastic disease?
– abnormalities of placentation resulting in tumor-like changes or malignant transformation
- includes Hydatidiform mole, Choriocarcinoma
375
What is Hydatidiform mole
– developmental abnormality of placenta
– trophoblastic proliferation, hydropic degeneration of chorionic villi
– enlarged uterus with no fetal movement, high HCG
376
Complete Hydatidiform mole vs. Incomplete Hydatidiform mole
Complete
– no identifiable fetus, abnormal fertilization (46XX, all paternal)
Incomplete
– usually some fetal parts, abnormal fertilization (69 chromosomes)
377
What is Choriocarcinoma?
– rare highly malignant tumor of placental origin, treat with methotrexate
378
Define abortion
– interruption of pregnancy prior to fetal viability (< 500 g, 20 wks)
379
What is a spontaneous abortion? How common?
– abortion with no identifiable cause (1/3 of all pregnancies)
380
What is a complete abortion?
– fetus and placenta expelled, normal function returns
381
What is a incomplete abortion?
– retention of some fetal or placental material
382
What is a missed abortion?
– death of fetus in utero, passed several weeks later
383
What is a threatened abortion?
– cervical os closed , spotting of blood
384
What is endometriosis? malignancy?
– endometrial tissue (uterine glands + stroma) located outside the uterus
– various locations, typically ovary, peritoneum
– benign, self-limited disorder that does not progress to cancer.
385
What it the pathogenesis involved in endometriosis?
* retrograde flow (reverse mensral flow - into ovaries e.g.)
| * traumatic implantation
386
What is a risk of endometriosis?
Infertility
387
What is acute mastitis? cause?
– acute inflammation of the breast
– lactating female
– bacterial infection
– abscess may develop
388
What is chronic mastitis?
inflammation of the breast
– rare disease of unknown etiology
– may mimic breast cancer
389
Describe a fibrocystic change in breast tissue. Age?
– benign changes in breast tissue due to various factors including hormonal influences and age
– fibrosis of intralobular stroma (stroma between lobes)
– cystic dilation of epithelial ducts
– epithelial hyperplasia
– various symptoms
- Females of reproductive age
390
What is Gynecomastia?
– increased proliferation of male breast due to various factors
391
What is fibroadenoma? Age?
– benign neoplasm of breast epithelial and stromal elements
– well circumscribed, firm, mobile mass
– young females
392
What is the most common cancer in females?
Breast cancer
393
What influences likelihood of breast cancer?
– hormonal, environmental and genetic influences
• familial breast cancers
– BRCA-1, BRCA-2 tumor suppressor genes
– increased incidence of other cancers
394
What are some risk factors of breast cancer?
```
• genetic predisposition
• hormonal factors
– prolonged estrogen exposure
» early menarche, late menopause
» nulliparous (woman who has never given birth)
• other malignancies
– contralateral breast carcinoma (breast cancer on other breast)
– endometrial carcinoma
• premalignant changes
– carcinoma in situ, atypical hyperplasia
• Age (white, 50-70 most common)
• Race
```
395
What is the most common breast cancer?
infiltrating ductal carcinoma
396
What is infiltrating ductal carcinoma?
* adenocarcinoma
* desmoplastic response of stroma
* lymphatic spread (axillary nodes drain most of the breast)
* presents as mass
397
How to detect breast cancer early?
– breast self-examination
| – mammography
398
What is therapy for breast cancer?
```
• Surgical resection
– lumpectomy
– mastectomy
– axillary dissection
• radiation
• chemotherapy
– tamoxifen
– herceptin
```
399
What is the prognosis for breast cancer?
Staging is most important
• histologic subtypes
• histological grading
• estrogen receptor status
400
What are osteocytes?
mature bone producing cells that maintain bone
401
What are osteoblasts?
bone forming cells that synthesize organic matrix
402
What are osteoclasts?
bone resorbing cells
403
What are the components of a synovial joint?
* ligamentous capsule
* synovial lining
* joint fluid
404
What is synathrosis?
an immovably fixed joint between bones connected by fibrous tissue
405
What is Achondroplasia? How is it inherited?
genetic disease
– autosomal dominant defect of bone formation resulting in dwarfism
– defective formation of long bones which do not lengthen
– normal trunk, short limbs, relatively large heads
– 80 % have normal parents (ie. new mutation)
406
What is Osteogenesis imperfecta?
developmental disease
– group of inherited diseases resulting from defective collagen type I
– results in production of osteopenic bone which is weak
– severe forms present with multiple fractures in fetus, usually fatal
– mild forms present with stunted growth, prone to fractures
407
What is Osteopetrosis?
genetic disease
– group of inherited diseases resulting from defective osteoclast function
– bones grow but not remodelled resulting in thick but brittle bones
408
What is Osteopenia?
– radiological term for a decreased amount of bone on x-ray
409
What is osteoporosis?
– form of osteopenia characterized by decreased bone mass
– may be localized (eg. immobilization of limb) or generalized
– may be primary or secondary
410
What is primary osteoporosis?
* an age related, accelerated bone loss, with no obvious cause
* the most prevalent bone disease
* multifactorial disease due to interplay of hormones, exercise, calcium
411
What is secondary osteoporosis?
* osteoporosis is secondary to a defined cause
| * causes include hormonal imbalance, diet, immobilization, drugs, tumours
412
What are some risk factors for osteoporosis?
* age (osteoporosis increases with age)
* genetic factors (osteoporosis runs in families)
* sex (females have accelerated bone loss after menopause)
* hormones (deficiency of estrogen results in accelerated bone loss)
* nutritional (inadequate Vitamin D, calcium)
* physical activity (inactivity promotes osteoporosis)
* environmental factors (smoking, alcohol promote osteoporosis)
413
What is type 1 primary osteoporosis? Who does it affect?
• typically occurs in post menopausal women
• due to increased osteoclast activity, affects bones with high percentage of cancellous bone (eg. Vertebrae- compression
fracture)
414
What is type 2 primary osteoporosis? Who does it affect?
(senile osteoporosis)
• affects both men and women
• pathogenesis not understood, affects cortical portion of long bones (eg. Femur - femoral fracture)
415
How do you diagnose primary osteoporosis?
* usually asymptomatic, found incidentally or after fracture
* recognizable on x-ray only after bone loss exceeds 30-40%
* bone density studies more effective
* usual bone markers are normal
416
What is Osteomalacia?
osteomalacia is a disease of adults due to inadequate mineralization of bone matrix in mature bones
417
What is rickets?
rickets is a disease of children due to inadequate mineralization of bone matrix in growing bones
418
What is the major cause of inadequate mineralization? and another cause
Vitamin D deficiency; hypophosphatemia
419
What are the causes of a Vitamin D deficiency?
– inadequate intake
– inadequate sunlight
– malabsorption
420
What is hypophosphatemia?
- decreased phosphate levels
causes of decreased phosphate include
– inadequate absorption
– excess loss
421
What is the pathogenesis of Osteomalacia and rickets?
* decreased absorption of Ca, PO (phosphate) from intestine
* increased Parathyroid hormone which causes increased bone resorption
* compensatory bone formation occurs in setting of inadequate minerals
422
How does inadequate mineralization manifest in children vs. adults?
Children - soft bones, deformity (bent)
Adults
• vague skeletal pain, gradual deformity of weight-bearing bones
• osteomalacia is reversible if supplement vitamin D, normalize calcium homeostasis
423
What is renal osteodystrophy?
renal osteodystrophy refers to bone changes that occur in patients with chronic renal failure (CRF)
– CRF results in ↓ phosphate excretion, ↓ decreased activation of vitamin D
– changes include osteomalacia, osteofibrosis, and osteitis cystica
424
What's the difference between Osteomalacia and osteoporosis?
- osteoporosis, the bones are porous and brittle, whereas in osteomalacia the bones are soft
- Osteoporosis, bones broken down faster than they can reform
- Osteomalacia - bones form, but don't mineralized well so they are weak
425
What is Paget's disease?
– chronic disease of unknown etiology characterized by irregular restructuring of bone with resulting thick and
deformed bones
– characteristic mosaic pattern on histology in osteosclerotic phase
426
What are the 3 phases of Paget's disease?
First, the destructive phase - by bone resorption.
Second, mixed phase -bone resorption is counterbalanced by new bone formation. Third, osteosclerotic phase - trabeculae appear irregularly thickened and the normal compact bone is replaced by wide, sclerotic, dense bone.
427
What is osteomyelitus and most common cause?
– inflammation of bones, most commonly due to bacterial infection
– bacteria reach bone via hematogenous or direct spread
• most common is Staphylococcal aureus
• mixed infections in trauma
• Mycobacterium tuberculosis infection in 1-3% of those with lung infection
• Treponema pallidum
428
What is treatment or osteomyelitis?
– treatment consists of antibiotics, +/- surgical drainage if necessary
429
What are some complications of osteomyelitis?
– complications include bone deformities, fractures, squamous carcinoma
– chronic osteomyelitis results from incompletely healed or persistent suppurative acute osteomyelitis
430
What is Aseptic necrosis (avascular necrosis, osteonecrosis)?
– death of part of a bone secondary to infarct
– infarct occurs as a consequence of ischemia
– if there is no obvious cause of the ischemia then called idiopathic
431
What is Legge-Calve-Perthe?
osteonecrosis of head of femur (3-10 yo boys)
432
What is a cause is osteonecrosis in the head of the femur in adults?
chronic alcoholism
433
What are some important identifiable causes of osteonecrosis?
* trauma
* corticosteroids
* radiation therapy
* systemic diseases (eg. sickle cell anemia, SLE)
* emboli
434
Comminuted fracture vs. closed fracture
– comminuted fracture has multiple fracture lines, fragments
– open (compound) fracture communicates with external environment
435
What are some examples of pathological ("spontaneous") fracture
• eg. Tumor, Paget’s disease, osteoporosis
436
How do stress fractures happen?
repeated minor trauma
437
What fills the gap between two different pieces of bone?
callus
438
What are the various changes that a callus can undergo?
* procallus formation (granulation tissue, cartilage, osteoid)
* fibrocartilage callus (increased collagen matrix)
* fibrosseous callus (haphazard bone spicules and connective tissue)
439
What are the benign primary bone tumours?
• osteoma, chondroma, fibroma
440
What are the malignant primary bone tumours?
* osteosarcoma
* chondrosarcoma
* Ewing’s sarcoma
441
What is osteosarcoma? Where does it usually affect?
– malignant neoplasm that produces bone
– various types based on location in relation to the bone
– preferentially affects metaphysis of long bones
– 60% occur around the knee joint
– invades locally, metastasizes via the bloodstream (lungs)
442
What is the most common primary bone tumour?
Osteosarcoma
443
When does osteosarcoma generally peak?
second decade of life
444
Mortality of osteosarcomas
aggressive tumors
• high mortality if no therapy
• combined chemotherapy and surgery curative in 80 %
445
What is chondrosarcoma? Where does it usually affect?
– malignant neoplasm that produces cartilage
– affects axial skeleton (pelvis, vertebra, shoulder, proximal femur)
– prognosis depends on resectability, grade of tumor, metastases
446
When does chondrosarcoma usually appear?
– peak incidence in fifth and sixth decades of life
447
What is ewing's sarcoma? Where does it occur? What is treatment?
– unusual malignant neoplasm consisting of undifferentiated cells
– diaphysis of long bones
– metastases are common (lungs, liver, brain)
– chemotherapy has improved prognosis
448
What is osteoarthritis?
Joint disease
| – chronic degenerative disease of articular joints with loss of cartilage
449
How common is osteoarthritis, what are the causes?
– very common, age related
– primary vs. secondary (previously damaged joints)
– cause unknown in most cases
• wear and tear hypothesis, possible metabolic derangement
450
How does osteoarthritis present, how is it diagnosed?
– variable clinical presentation, relieved with rest
– monoarticular or polyarticular distribution, asymmetric
– weight bearing joints, DIPs and PIPs
– diagnose on basis clinical/radiology
451
What is rheumatoid arthritis?
– chronic systemic disease of unknown etiology characterized by inflammation of joints and variable
extra-articular features
452
What causes rheumatoid arthritis?
– pathogenesis unknown, genetic susceptibility in certain individuals
453
How does – pathogenesis unknown, genetic susceptibility in certain individuals present?
– may affect any joint, usually symmetric distribution , metacarpophalangeal joints (knuckles); proximal interphalangeal joints (PIP)
– variable clinical course
• swelling of joint, erosion of bone by pannus (granulation tissue)
• immobilization of joint, ankylosis (joint stiffening), bony deformities
– extra-articular features
• rheumatoid nodules (firm lumps), lung disease, eye disease, vasculitis, anemia
454
What is rheumatoid factor?
* autoantibody directed against part of IgG (present in 80 % of rheumatoid arthritis cases)
* not diagnostic of rhematoid arthritis (may occur in SLE)
455
What is infectious arthritis?
inflamation of the joints from a bacterial or viral infection such as lyme disease
456
What is lyme disease?
* Borrelia burgdorferi, carried by ticks
* skin rash + migratory arthritis several weeks after tick bite
* second stage may involve heart, CNS, arthritis
* in 10%, chronic arthritis develops
457
What is gout?
– disease characterized by hyperuricemia and deposition of uric acid crystals in various tissues including joints
– multifactorial trait
– tophaceous deposits are aggregates of uric acid in soft tissue
458
Where is the most classically affected area for gout?
Big toe - monoarthritis
459
What is the age of onset for gout?
20-40; usually males
460
What are some complications associated with gout?
bony deformities with chronic disease, renal calculi most important complication
461
What is ankylosing spondylitis? What is it associated with? Who is most likely to be affected?
joint disease
(a progressive disease of unknown origin. It results in obliteration of intervertebral joints and stiffening of the vertebral column)
– seronegative arthropathy preferentially affecting spine, sacrum
– destuction of joints with fusion of spine
– limited chest expansion and back pain initial symptoms
– asymmetrical peripheral joint involvement
– > 90% have HLA B-27
- Males most likely to be affected
462
What are the 2 skeletal muscle functions?
– contraction (movement, heat, posture, breathing)
| – storage ( glycogen, fat)
463
myotonus
– continuous contraction
464
What is fibrillation?
– uncoordinated contraction of groups of fibers
465
What is myalgia?
muscle pain
466
What is neurogenic atrophy?
• Form of muscle atrophy caused by injury to nerve supplying the muscle
467
What are the some examples of upper motor neuron injuries and their complications?
* cortex lesion (stroke, amyotrophic lateral sclerosis)
* cortical tract lesion (stroke)
* spinal tract injury (trauma)
468
What are the some examples of lower motor neuron injuries and their complications?
* spinal nerve disease (poliomyelitis - polio)
* nerve root compression (ruptured disk, ankylosing spondylitis)
* axonal injury (trauma, autoimmune, toxin)
* axonal branch injury (diabetes, atherosclerosis)
469
What is myasthenia gravis? What is it characterized by?
– autoimmune disease due to immune -mediated injury resulting in decreased numbers of muscle ACh receptors
– antibodies directed against ACh receptor
– bind to receptor thereby preventing ACh from binding
– characterized by easy fatigability and weakness
– most patients have thymic hyperplasia or neoplasm of the thymus
470
How is Myasthenia gravis diagnosed?
```
– diagnosed by clinical changes
– confirmed with specific tests
• anticholinesterase test
– transient improvement in symptoms due to increased presence of Ach
• identify antibodies to Ach receptor
```
471
What are Muscular dystrophies?
Heterogeneous group of inherited primary muscle diseases characterized by progressive muscular weakness
and wasting
472
What is duchenne muscular dystrophy?
– most common dystrophy caused by deficiency of dystrophin an integral protein in cell plasma membrane
(including skeletal muscle cells)
– gene for dystrophin protein is located on X-chromosome
473
How is duchenne muscular dystrophy inherited?
– X-linked recessive inheritance, males affected
474
What are some characteristics of duchenne muscular dystrophy and how is it diagnosed?
```
– weakness by age 5, wheelchair by age 10-12, death in early twenties
– reduced intelligence
– diagnosis
• typical clinical findings
• family history
• laboratory tests
```
475
Duchenne vs becker muscular dystrophy
Becker
– same gene affected but milder disease
– less common, symptoms begin in pubery, live 40-50 yr
476
What is Myotonic dystrophy? How is it inherited?
– second most common muscular dystrophy
– mutation of myotonin protein kinase
– autosomal dominant inheritance, symptoms develop in adults
477
What are some characteristics of myotonic muscular dystrophy?
– muscle wasting, mental deterioration and diabetes
– myotonia
• sustained involuntary contraction of a group of muscles
– facial muscle weakness (“hatchet man” faces)
478
What are myopathies? Congenital vs. acquired?
disease of the muscle in which the muscle fibers do not function properly
Congenital myopathies
– group of muscle diseases characterized by onset early in life, non-progressive or slowly progressive course,
proximal or generalized muscle wasting and hypotonia (floppy baby) or severe joint contracture
Acquired myopathies
– nonspecific term for muscle weakness secondary to identifiable cause
– include muscle disease due to various metabolic and hormonal diseases
479
What are 2 examples of acquired myopathies and their characteristics?
– diabetic myopathy
• vascular, metabolic, and neuogenic components
– cancer myopathy
• paraneoplastic syndromes
480
What is myositis
infammation of muscle
481
What are some examples of infectious myositis
– viral myositis
• fleeting, self-limited (eg. Influenza virus)
• Coxsackie B associated with muscle pain, may have myocarditis
– bacterial myositis
• localized infection
• Tetanus and gas gangrene are serious complications of wounds infected with clostridia
– parasite
• Trichinella spiralis-undercooked pork
482
What is immune myositis and some examples?
```
– polymyositis
• limited to muscles
– dermatomyositis
• muscles + other organs including skin
– lupus associated myostis
– Sarcoidosis
```
483
What are the benign neoplasms of muscle and soft tissue?
– fibroma tumours (composed of fibrous tissue), lipoma (benign tumor made of fat tissue), hemangioma (enign tumor derived from blood vessel cell types)
484
What is rhabdomyosarcoma?
* malignant neoplasm derived from skeletal muscle cell
| * peak incidence in childhood
485
What is malignant fibrous histiocytoma?
• malignant neoplasm of undifferentiated connective tissue cells
486
What is liposarcoma?
• malignant neoplasm derived from adipocytes
487
What are 2 congenital diseases of the skin?
– nevus (mole/birthmark)
| – albinism (melanin absence)
488
What are the features of the 3 degrees of burns?
– first degree (erythema and swelling)
– second degree (blisters)
– third degree (dermis involved)
489
What are 3 examples of idiopathic and immune diseases of the skin?
– eczema (chronic inflammatory skin condition)
– seborrheic dermatitis ( a chronic form of eczema)
– psoriasis (skin condition that speeds up the life cycle of skin cells)
490
What is basal cell carcinma of the skin? prognosis?
• common malignant epithelial neoplasm, excellent prognosis
491
What is squamous cell carcinoma of the skin? prognosis?
• common malignant epithelial neoplasm,good prognosis
492
What is melanoma?
– malignant neoplasm originating from melanocytes
493
What are the different types of melanoma and their features?
* lentigo maligna (in situ that consists of malignant cells but does not show invasive growth)
* superficial spreading ( skin cancer that slowly grows horizontally across the top layer of skin before moving to the deeper layers)
* nodular ()grow more rapidly in thickness (penetrate the skin) than in diameter
* acral-lentiginous (skin cancer that appears on the palms of the hands, the soles of the feet, or under the nails)
494
What is an important prognostic factor for melanoma?
Depth
495
What clinical features are worrisome for melanoma?
* A - asymmetry
* B - border irregularity
* C - color irregularity
* D - diameter > 6 mm
496
What are mass lesion endocrine glad disorders usually caused by?
neoplasia or hyperplasia
497
What is multiple endocrine neoplasia syndrome (MEN)?
literally syndromes that are caused by multiple endocrine neoplasms
498
What is MEN I?
multiple endocrine neoplasias
| pituitary, parathyroid, pancreatic islet cell neoplasia
499
What is MEN IIa?
multiple endocrine neoplasias
| medullary thyroid carcinoma, pheochromocytoma, parathyroid
500
What is MEN IIb?
multiple endocrine neoplasias
| IIa + skin and mucosal nerve tumors
501
What re the 2 parts of the pituitary gland? Functions?
Posterior pituitary (extension of the hypothalamus)
– secretes the hormones ADH, and oxytocin
Anterior pituitary
– secretes growth hormone, thyroid stimulating hormone, adrenocorticotropin hormone, gonadotrophin
hormones
– release of hormones controlled by other hormones released by hypothalamus and various feedback loops
502
What is pituitary ademona? where do symptoms come from?
– benign neoplasm of endocrine cells in the anterior pituitary
– symptoms due to release of excess hormones or pressure effects of mass (compression of pitutary stalk and/or
optic chiasm)
– endocrine effects depend on what hormone produced by the adenoma
503
What is prolactinoma (LH)?
pituitary adenoma that produces prolactin
504
When is prolactinoma usually identified? what is treatment?
– identified earlier in young reproductive female because present with amenorrhea, galactorrhea, infertility
(microadenoma)
– surgery or medical therapy (bromocryptine) to remove
505
What are somatotropic adenomas and what are they do they result in?
Pituitary adenoma
– neoplastic cells produce growth hormone
- gigantism and acromegaly
506
Gigantism vs. acromegaly
Gigantism - results from excess growth hormone before growth plates close
• generalized increase in body size with disproportionately long legs, arms
Acromegaly - results from excess growth hormone after puberty
• enlargement of hands, feet, jaw, tongue, and soft tissue)
507
What is corticotropic adenoma? resulting syndrome?
– neoplastic cells produce adrenocorticotropin hormone
– Cushing’s disease refers to the syndrome resulting from excess glucocorticoid release by the adrenal cortex
due to excess ACTH
508
What are the causes of pituitary hypofunction?
* congenital defect of pituitary gland (primary dwarfism)
* destructive tumor (pituitary adenoma)
* ischemia of the pituitary gland (Sheehan’s syndrome)
509
What are symptoms of pituitary hypofunction?
– weakness, ↓ appetite, ↓ weight, hypotension, amenorrhea
| – secondary hypofunction of target organs
510
What is diabetes insipidus and what causes it?
– lack of ADH
– usually due to destructive lesion in hypothalamus, pituitary
– unable to resorb water, large amounts of hypotonic urine
511
What is the role of the pituitary on the thyroid?
release of thyroid hormones controlled by TSH (from pituitary)
512
What are the hormones produced by the thyroid?
T4, T3, calcitonin
513
What causes hyperthyroidism?
– major causes are Grave’s disease (autoimmune), some multinodular goiters, tumors
514
What are the symptoms of hyperthyroidism?
restless, nervous, emotional lability, sweating, tachycardia, diarrhea, weight loss with increased appetite
515
What is grave's disease?
– autoimmune disease due to antibodies targeting the TSH receptor on thyroid follicular cells
– AB binds to TSH receptor causing release of thyroid hormones
– more common in females
– associated with other autoimmune diseases
– exopthalmos occurs in Grave’s disease
516
What is a multinodular goiter?
– enlarged, nodular thyroid may produce increased amounts of thyroid hormone (some may be euthyroid (normal levels) or
hypofunctioning)
517
What are the causes of hypothiroidism?
agenesis, surgery, thyroiditis, iodine deficiency
518
What are the symptoms of hypothyroidism? (children vs. adults) how to treat?
– cretinism and dwarfism if occurs in perinatal period or infant
– myxedema if occurs in older child or adult
• sleepy, tire easily, cold intolerance, constipation, weak
– treat with thyroid hormone replacement
519
adenoma vs. carcinoma of the thyroid
Adenomas
– benign neoplasms of thyroid follicular cells
– may produce symptoms due to mass effect
– treated by surgery (microscopic examination required to rule out cancer)
Carcinoma
– malignant neoplasm of thyroid follicular cells
520
What are the 2 major types of thyroid carcinomas and their prognoses?
* papillary carcinoma (80%)- good prognosis
| * follicular carcinoma (15%)- relatively good prognosis
521
What is the function of the parathyroid?
– produce parathyroid hormone (PTH), involved in calcium homeostasis
522
What causes hyperparathyroidism?
parathyroid adenoma and parathyroid hyperplasia
523
What are the symptoms of hyperparathyroidism?
(hypercalcemia)
| – bones, stones, moans, abdominal groans
524
What are the causes of hypoparathyroidism?
surgery, congenital hypoplasia
525
What are the symptoms of hypoparathyroidism?
(hypocalcemia)
| – muscle spasms, irregular heart beat, cardiac arrest (if severe)
526
What are the areas of the adrenal gland and what hormone do they secrete?
```
adrenal cortex
– zona glomerulosa (aldosterone)
– zona fasciculata (cortisol)
– zona reticularis (secondary sex steroids)
adrenal medulla
– secrete epinephrine, norepinephrine
```
527
What is Conn's syndrome?
Hyperaldosteronism
– syndrome due to excess mineralocorticoid hormone (aldosterone)
– causes include adrenocortical adenoma and adrenal hyperplasia
– present with hypertension and hypokalemia
528
What is Cushing's syndrome?
Hypercortisolism
– syndrome due to excess glucocorticoid hormones (cortisol)
– dramatic appearance: central obesity, buffalo hump, moon face, striae
529
What are the most common causes of Cushing's syndrome?
* adrenal hyperplasia or neoplasia
* hypersecretion of ACTH by pituitary gland (Cushing’s disease)
* ectopic ACTH (paraneoplastic syndrome)
530
What usually causes Adrenocortical hypofunction?
autoimmune destruction of adrenals, also due Tb, malignancy
531
What is Addison's disease? Symptoms?
– autoimmune destruction of adrenal gland
| – fatigue, weight loss, nausea, increased infections, low Na, high K
532
What is a neuroblastoma?
Disease of Adrenal Medulla
– malignant neoplasm of neuroblasts (primitive cells) in neonates, infant
– treatment with chemotherapy, surgery, radiation (90 % cure)
533
What is Pheochromocytoma?
– a neoplasm (usually benign) derived from adrenal medulla cells
– diagnosed on basis of dramatic clinical picture, metabolites in urine
– treated by surgery
534
What does diabetes mellitus present with?
– present with polyuria, polydypsia (excessive thirst), weight loss
535
Describe the pathogenesis of diabetes
– insulin released in response to increased blood sugar
• insulin required by certain cells for entry of glucose into the cell
– insulin decreases blood glucose levels
– lack of insulin causes hyperglycemia
• present with polyuria (osmotic diuresis) and resulting polydypsia
• also fatigue due to inability of glucose to enter certain cells
– striated muscle cells must use anaerobic glycolysis
• increased lactic acid
• decreased use of fats result in increased free fatty acids
– free fatty acids oxidized into ketones (acidosis)
536
What are some complications associated with Diabetes mellitus?
– Cardiovascular [increased atherosclerosis (CAD, CVD, distal gangrene)]
– Renal [glomerulosclerosis, pyelonephritis, papillary necrosis]
– Eyes [diabetic microangiopathy of retinal vessels, glaucoma, cataracts]
– Nervous system
537
What is the treatment for diabetes?
Depends on type
– type 1 requires insulin
– type 2 diet, oral hypoglycemics, insulin if unable to control
538
What are the meninges?
– specialized layers of connective tissue surrounding the brain
• dura mater, arachnoid mater, pia mater
539
What are brain tumours in adults genterally, why?
* brain tumors in adults are gliomas
| * loss of neurons not replaced, neural cell tumors occur in children
540
What are Dysraphic malformations?
Developmental disorders
| – group of congenital malformations characterized by incomplete closure of the neural tube, or bones protecting the CNS
541
Cranial vs. spinal dyraphism
Cranial
– group of congenital malformations characterized by incomplete closure of the neural tube, or bones protecting
the CNS
Spinal
(incomplete closure of posterior spine)
- meningocele, myelomeningocele, spina bifida
542
What is Meningocele?
Spinal dysraphism
| - defect with protrusion of meninges through defect
543
What is Myelomeningocele?
Spinal dysraphism
| protrusion of meninges and part of spinal cord
544
What is Spina bifida?
Spinal dysraphism
absence of vertebral arch, typically aaccompanied by neurologic defects affecting lower
extremities
545
What is an epidural hematoma? What is cause?
– arterial hemorrhage into space between skull and dura
| – usually due to trauma, not immediately apparent
546
What is a subdural hematoma? What is cause?
– venous hemorrhage into space between dura and arachnoid
| – usually due to repeated trauma (alcoholic, elderly)
547
What is a subarachnoid hematoma? What is cause?
– hemorrhage from vessels into space between arachnoid and pia
– usually due to trauma, also rupture of aneurysm (Berry aneurysms)
548
What is a intracerebral hematoma? What is cause?
– hemorrhage into substance of the brain from intracerebral vessels
– trauma, stroke
549
What are two major patterns of global ischemia? what are characteristics of both?
– two major patterns of injury are multiple small foci and hypoperfusion
– multiple foci of ischemic necrosis may occur due to atherosclerosis
– results in multi-infarct dementia (slow progressive mental deterioration)\
– hypoperfusion ischemia (“watershed” infarcts)
• region furthest from blood supply most susceptible to hypotension
• get infarction of the border zones
550
What is focal ischemia? How does it usually present?
– ischemic necrosis of localized part of cerebral cortex
| – usually presents as a stroke (a permanent neurologic deficit)
551
What is the most common site of focal ischemia?
middle cerebral artery
552
What is a hemorrhagic stroke? most common cause?
– strokes resulting from rupture of blood vessel no occlusion
– hypertension
• chronic severe systemic hypertension is most common cause
• usually occur in the basal ganglia
553
Concussion vs. contusion vs. laceration
– concussion is a transient loss of consciousness following blunt trauma
– contusion (“bruising”) is disruption of blood vessels due to trauma
• coup lesion (damage at site of impact)
• contrecoup lesion (damage opposite site of impact)
– laceration (“tearing”) is severe form of brain injury with tearing of brain
• motor vehicle accident
554
Hyperextension vs. hyperflexion injuries
– hyperextension injury, a force to the forehead forces head backwards
– hyperflexion injury, impact on the occiput forces head forwards
555
What are the routes of infection for CNS infections?
– vascular spread (most common)
– direct extension from adjacent structures
– ascending neural route (eg. Rabies)
556
Myelitis vs. encephalitis vs. meningitis
Forms of CNS infections
– myelitis is inflammation of spinal cord parenchyma (poliomyelitis)
– encephalitis is inflammation of cerebral parenchyma (viral)
– meningitis is inflammation of the meninges
557
Leptomeningitis vs. meningoencephalitis
* leptomeningitis is inflammation confined to the subarachnoid space
* meningoencephalitis is inflammation that spreads into brain
558
What typically causes acute meningitis?
Bacterial infection
– Neisseria meningitidis, Streptococcus pneumoniae most common
• Neisseria more common in children, streptococcus in adults
559
What typically causes chronic meningitis?
* Tuberculosis
* fungal infections (inmmunocompromised)
* Lyme disease
* syphilis
560
What usually causes encephalitis?
viruses
561
How does HIV affect the CNS?
* AIDS related dementia is due to a subacute encephalitis
| * AIDS are at risk for opportunistic infections (toxoplasmosis)
562
What viruses selectively affect the CNS?
(rabies, tick borne viruses)
563
Which viruses are systemic, but also affect CNS?
(herpes, measles, rubella)
564
What are Prions?
– small infectious protein particles with unusual structure
565
What are some examples of Prion diseases?
– prion diseases include Creutzfeldt-Jakob disease, variant CJD
– Bovine spongiform encephalopathy is
prion disease in cows
- brain undergoes spongiform degeneration
566
What fungi are involved in CNS infection?
– Candida, Aspergillus, and Cryptococcus may cause CNS infections in immunocompromised individuals
567
What is multiple sclerosis?
– demyelinating disease of probable autoimmune origin
| – characterized by chronic relapsing and remitting course
568
What is prevalence of MS?
– affects 1-2 persons per 1000, usually 25 to 45 yo
569
What is the pathogenesis of MS?
– pathogenesis not known
• more prevalent in colder climates
• genetic component
• immunologic studies (t-lymphocytes, B lymphocytes)
570
What is Tay-Sachs's disease?
Inborn errors of metabolism
| • hexosaminidase (lysosomal enzyme) deficiency results in accumulation of gangliosides
571
What is Niemann-Pick?
Inborn errors of metabolism
| sphingomyelinase deficiency results in accumulation of sphingomyelin (phospholipid)
572
What does a Thiamine deficiency cause?
CNS lesions
| Wernicke-Korsakoff syndrome (ocular function, gait, mental function)
573
What does a B12 deficiency cause?
CNS lesions
| Uncoordinated movement, sensorimotor peripheral neuropathy
574
What does a Nicotinic acid deficiency cause?
cause CNS lesions
| dermatitis, diarrhea, delirium
575
What are the acute effects of alcohol on CNS?
* depressant
| * neurotoxic
576
What are chronic effects of alcohol on CNS?
```
• thiamine deficiency
• B12 deficiency
• cerebellar atrophy
• cortical atrophy
subdural hematomas
delirium tremens
```
577
What are the histological changes of Alsheimer's disease?
– atrophy of frontal and temporal lobes
| – histological changes include neuritic plaques, neurofibrillary tangles
578
What is Parkinson's disease? how does it present?
– decreased dopaminergic neurons in the substantia nigra
| – present with rigidity, akinesia, tremor
579
What is Huntington's disease?
– neurodegenerative disease characterized by involuntary, gyrating movements and progressive dementia
580
How is Huntington's disease inherited?
– autosomal dominant
581
What is Amyotrophic lateral sclerosis ?What causes mortality?
– progressive, fatal motor neuron disease of unknown etiology
– characterized by motor weakness and wasting of muscles in extremities leading to muscle loss and death
– loss of motor neurons in spinal cord
– death due to paralysis of respiratory muscles within few years
582
What are some general facts on CNS neoplasms?
– incidence is low
– account for 2% of cancer deaths in adults, 20% in children
– usually no identifiable risk factor
– some hereditary syndromes
583
What are the 2 primary CNS neoplasms?
– Gliomas (tumor that starts in the glial cells)
| – Meningiomas (neoplasm arising from meninges, usually benign, good prognosis)
584
What are the 2 types of gliomas
Astrocytoma (malignant neoplasms with appearance of astrocytes )
Medulloblastoma (cerebellar tumor of childhood, poor prognosis)
585
What is glioblastoma multiforme?
Astrocytoma
– highly aggressive, poor prognosis (mean survival 1 yr)
– irregularly infiltrative lesion
– cerebellum
Pathology 375
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