Thyroid Storm

Thyroid storm is a sudden, life-threatening exacerbation of thyrotoxicosis. Some series suggest a mortality rate of between 30 and 75%. 
Its manifestations are due to the action of excess thyroid hormone. 
Fever is the most characteristic feature, with the temperature often rising above 41°C. There may be evidence of organ damage. 
The clinical picture is frequently clouded by a secondary infection such as pneumonia or a viral infection. 
Death may be caused by cardiac arrhythmia, congestive heart failure, hyperthermia or other unidentified factors. 
The diagnosis of thyroid storm is made entirely on clinical grounds. The results of thyroid function tests will rarely be available soon enough to make the diagnosis. 
Propylthiouracil followed by a stable iodine preparation (eg Lugol’s iodine) is usually given. 
Propranolol, intravenous fluids, dexamethasone and cooling are also often required. Finally, one must remember to treat the precipitating cause.

Management of Acute Heart Failure

Sit the patient upright

Oxygen
100% if no pre-existing lung disease

IV access and monitor ECG

Treat any arrhythmias, eg AF 

Investigations whilst continuing treatment

Furosemide 40–80mg IV slowly
Larger doses required in renal failure

GTN spray 2 puff s SL or 2 ≈ 0.3mg tablets SL
Don’t give if systolic BP <90mmHg

Necessary investigations, examination, and history

If systolic BP ≥100mmHg, start a nitrate infusion,
eg isosorbide dinitrate 2–10mg/h IVI; keep systolic BP ≥90mmHg

If the patient is worsening:
• Further dose of furosemide 40–80mg
• Consider CPAP—improves ventilation by recruiting more alveoli, driving fl uid out
of alveolar spaces and into vasculature (get help before initiating!)
• Increase nitrate infusion if able to do so without dropping systolic BP <100
If systolic BP <100mmHg, treat as cardiogenic shock and refer to ICU

Naso gastric Fedding

The first line test for determining the site of a nasogastric feeding tube is pH testing of aspirate from the tube. If the pH is between 1 and 5.5 feeding may be commenced. 
If an aspirate cannot be obtained (various manoeuvres can be attempted) or the pH is> 5.5 then a chest x ray should be performed to determine positioning. 
If the pH reading is between 5.5 and 6 it is recommended that a second independent reading is made to confirm. 
According to National Patient Safety Association guidance on the use of nasogastric feeding tubes feeding cannot be commenced if aspirate is obtained with a pH ≥6. 
The guidance advises that aspirate appearance, litmus paper testing and 'whoosh' testing should not be used in determining nasogastric tube placement as they are not reliable.

Hepatitis Antibodies

Presence of HBsAg in the serum is indicative of active HBV infection, either acute or chronic. 
Antibodies against hepatitis B core antigen (anti-HBc) are only detected in individuals who have been infected with HBV. As with other antibodies generated in response to infection IgM is present during the initial immune response, this is replaced over time by IgG antibodies. 
Anti-HBc IgG is produced from around 14 weeks after exposure, in the absence of anti-HBc IgM it may indicate cleared or chronic HBV infection. 
Presence of hepatitis C antibodies indicates exposure to the virus, if detected a viral RNA load is required to determine whether there is active infection. 
Persistence of viral RNA in the bloodstream more than six months after exposure (or acute illness if symptoms develop) indicates chronic infection. 
Antibodies against hepatitis B surface antigen (anti-HBs) indicate a vaccinated individual (the vaccine is based upon the HBsAg protein) or previous infection with HBV (seroconversion to produce anti-HBs in the setting of HBV infection indicates the infection has been cleared). 
Anti-HBc IgM is detectable between six and 32 weeks after exposure and indicates acute HBV infection. 
Acute hepatitis C infection is asymptomatic in 60-70% of cases, infection is chronic in around 85% of individuals.

Maturity-onset diabetes of the young (MODY)

It is characterised by the development of type 2 diabetes mellitus in patients < 25 years old. It is typically inherited as an autosomal dominant condition.

It presents most commonly in early adulthood and is associated with severe hyperglycemia in some cases and frequent microvascular complications.
Ketosis is not a feature at presentation
Over six different genetic mutations have so far been identified as leading to MODY.

● MODY 3
60% of cases
due to a defect in the HNF-1 alpha gene

● MODY 2
20% of cases
due to a defect in the glucokinase gene

●MODY 1
mutation of HNF4alpha
is much less common and presents later.
it is responsive to sulphonylureas although insulin may be required.

●MODY 5
mutation in HNF1beta
leads to renal cysts and proteinuria as well as diabetes.

● MODY 4
IPF1 mutation

●MODY 6
NeuroD1 mutation

Management

One third of patients require insulin therapy and around one-third may be controlled on oral hypoglycaemic drugs.
Sulphonylureas would be the initial oral therapy of choice.

Important Points with Definitions to Remember in General Pathology

1. Hyperplasia is an increase in the number of cells in an organ or tissue, usually resulting in increased volume of the organ or tissue.
2.   Hypertrophy refers to an increase in the size of cells, resulting in an increase in the size of the organ.
3. Atrophy is the shrinkage in the size of the cell by loss of cell substance.
4.  Metaplasia is defined as a reversible change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type.
5. Cell swelling is the earliest sign of a reversible cell injury.
6.  Free radical is a chemical species that have a single unpaired electron in an outer orbit.
7. Necrosis is a spectrum of morphological changes that follow cell death in a living tissue largely resulting from the progressive degradative action of enzymes on the lethally injured cell.
8.  Necrosis has six major type; coagulative, Caseous, Liquefactive, fibrinoid,gangrenous and Fat.
9.  Apoptosis (Greek falling off) is defined as a pathway of programmed cell death that is aimed at a highly regulated intracellular programme in which cells destined to death by activated enzyme that degrade the cell’s DNA and nuclear and cytoplasmic proteins.
10.  Morphologically an apoptotic cell shows: a) cell shrinkage, b) chromatin condensation c) formation of cytoplasmic blebs and apoptotic bodies, d) phagocytosis by macrophages.
11. Apoptosis has two phases a) Initiation phase   extrinsic and intrinsic pathways b)Execution phase c)phagocytosis of dead cell.
12. Genes promoting apoptosis are: bax,bak,bim
13.  Genes inhibiting apoptosis are bcl 2 family.
14.  Initiator caspase are 8 & 9, while executioner caspases are mainly 3 & 6
15.  Dystrophic calcification is always seen in damaged tissues while metastatic calcification may occur in normal tissues whenever there is hyperplasia.
16.  Inflammation is a complex reaction to injurious agents such as microbes and damaged, usually necrotic cells that consists of vascular responses, migration and activation of leukocytes, and systemic reactions.
17.  Inflammatory response consist of TWO main components: vascular & cellular, and divided into TWO main patterns: Acute and Chronic.
18.  Vasodilatation is one of the earliest manifestation of acute inflammation, if follows a transient vasoconstriction of arterioles lasting few seconds.
19.  Increased vascular permeability leading to the escape of a protein-rich fluid (exudate) into the extravascular tissue in the HALL MARK of acute inflammation.
20.  Formation of endothelial gaps in venules is the most common cause of vascular leakage.
21.  Leukocytes Adhesion molecular families have a major classes: a) Selectins (E,L & P types), b) Integrins, c) Immunoglobulin family of adhesion molecules and d) Mucin like glycoproteins.
22.  Selectins mainly involved in rolling of leukocytes, PECAM in transmigration and immunoglobulin family in adhesions.
23.  Chemotaxis is defined as uni directional migration of leukocytes towards the site of injury under chemical gradient action.
24.   Most important chemotactic agents are C5a,LTB4 and bacterial products.
25.  Major opsonins are: C3b & Fc fragment of IgG protein.
26.  H202-MPO-Halide systein is the most efficient bactericidal system in neutrophils.
27. Chediak-Higashi Syndrome is an autosomal recessive condition characterized by failure of fusion of phagosome with lysosome.
28.  Chronic granulomatous disease of childhood results from inherited defects in the components of NAPDH oxidase which generates superoxide, leading to body infections.
29.  Vasoactive amines are histamine and serotonin which are the main players of early inflammation.
30.  Plasma Proteins are: Complement system proteins, clotting system and fibrinolytic system.
31.  Prostaglandins are vasodilators.
32.  MAC (C5B6789) is the membrane attack complex, which finally kills the bacteria.
33.  Activated Hageman factor initiates FOUR systems involved in inflammatory responses Kinin, Clotting, fibrinolytic and complement system
34.  SRS-A (slow releasing substance of anaphylaxis) constitutes LTC4, LTD4 & LTE4 promote vasoconstriction, bronchospasm & increased vascular permeability.
35.   Lipoxins are bioactive products generated from transcellular biosynthetic mechanisms involving neutrophils and platelets.
36.  IL-1 & TNF are two of the MAJOR cytokines that mediate inflammation.
37.  Major chemokines include: IL-8, MCP-1, eotaxin, MIP-1, Lymphotactin and RANTES.
38.  Nitric oxide plays major role in production of vasodilation by relaxing vascular smooth muscle in ischemic conditions.
39.   The major mediators of pain are Bradykinin & Prostaglandins
40.  Potent vasodilators are : Vasoactive Amines, Prostaglandins & NO.
41.  Acute inflammation is defined as a rapid response to an injurious agent that serves to deliver mediators of host defense – leukocytes and plasma proteins to the site of injury.
42.  Chronic inflammation is defined as an inflammation of prolonged duration, in which active inflammation, tissue destruction and attempts at repair are proceeding simultaneously.
43.  Neutrophils are the main cells of acute inflammation (exudates) while Mononuclear cells (with one nucleus are the main cells of chronic inflammation .Mononuclear cells include Lymphocytes, Monocytes, Macrophages and Plasma cells.
44.  Macrophages are the prima donna (main working cell) of chronic inflammation, while lymphocytes are present in increased number.
45. Granuloma is a focus of chronic inflammation, consisting of microscopic aggregation of macrophages that are transformed into epithelium like cells surrounded by a collar of mononuclear leukocytes. Don’t confuse it with Granulation tissue which has capillaries, fibroblasts, and a variable amount of inflammatory cells.
46.  Classical tuberculous granulomas is composed of epithelioid cells, Langhan’s multinucleated giant cells, caseation necrosis and collar of lymphocytes. There are two types of Granulomas: Immune & foreign body.
47.  There are 3 types of cells in the body: Continously dividing labile cells, Quiscent or stable cells and Permanent Non-dividing cells.
48.  Stem cells are cells characterized by their prolonged self renewal capacity and by the asymmetric replication. They are of two types: embryonic & adult stem cells.
49. VEGF & fibroblast Growth factor are mainly involved in angiogenesis.
50. TGF-B is a growth inhibitor for most epithelial cells and leukocytes, potent fibrogenic agent and  a strong anti-inflammatory effect.
51.  Extracellualr matrix is formed of these groups of molecules : a) fibronectin b) adhesive glycoproteins and c) proteoglycans & hyaluronic acid.
52. Collagens is the most common protein in the animal world, with 27 types discovered so far. Types I, II, III, V & X) are fibrillar and most common while type IV is non fibrillar.
53.  Healing by 2^nd intention differs from 1^st intention in three ways; a) inflammatory reaction is more intense, b) Much more granulation tissue forms and c) wound contraction phenomenon.
54.  Accumulation of excessive amounts of collagen may give rise to a hypertrophic scar while if scar tissue grows beyond the boundaries of the original wound and does not regress, it is called keloid.
55.  Edema is defined as accumulation of fluid in the interstitial tissue spaces and body cavities.
56.  Local increased volume of blood in a particular tissue leads to Hyperemia and congestion. Hyperemia is an active process, resulting from augmented tissue inflow because of arteriolar dilation while Congestion is a passive process resulting from impaired outflow from tissue.
57. Heart failure cells are hemosiderin laden macrophages seen in chronic pulmonary congestion.
58.  Petechiae are minute 1 to 2 mm hemorrhages into skin, mucous membranes or serosa surfaces, while >3 mm hemorrhages are called Purpura and more larger > 1 to 2 cm subcutaneous hematomas are called Ecchymoses.
59.  Virchow’s triad include: a) Endothelial injury b) Stasis or turbulent blood flow & c) blood hypercoagulability.
60.  Of the inherited causes of hypercoagulability, mutation in the factor V gene and prothrombin gene are the most common.
61.   Lines of Zahn are laminated lines produced by alternating pale layers of platelets admixed with some fibrin and darker layers containing more red cells.
62.  Fate of thrombus include: propagation embolization, dissolution, organization and recanalization.
63.  Embolus is a detached intravascular solid, liquid or gaseous mass that is carried by the blood to a site distant from its point of origin. The phenomenon is called embolism.
64.  Infarct is an area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage in a particular tissue.
65.  The most dominant histologic characteristic of infarction is ischemic coagulative necrosis.
66.  Shock is the systemic hypoperfusion caused by reduction either in cardiac output or in the effective circulating blood volume, and resulting in hypotension followed by impaired tissue perfusion and cellular hypoxia.
67.  Major types of shock include: cardiogenic, hypovolemic, septic, neurogenic and anaphylactic.
68.  Mutation is defined as a permanent change in the DNA.
69. Marfan’s syndrome is a disorder of the connective tissue of the body, characterized by changes in the skeleton, eyes and cvs. Mainly cause by defects in an extracellular glycoprotein Firbillin-1.
70.  Ehlers-Danlos Syndrome comprise a clinically and genetically heterogenous groups of disorders that result from some defect in the syntesis or structure of fibrillar collagen.
71. Amyloid is a pathologic proteinaceous substance deposited between cells in various tissues and organs of the body in a wide variety of clinical settings.
72.  Neoplasm is an abnormal mass, the growth of which exceeds and in uncoordinated with that of the normal tissue and persists in the same excessive manner after cessation of the stimuli which evoked the change.
73. Tumor has two basic components: Parenchyma & stroma, while tumors are of two types: Benign and Malignant.
74.  Benign tumors are well differentiated, grow slowly and don’t show invasion and metastases, while Malignant tumors range from well to undifferentiated, grow fast and show invasion and metastasis.
75.  Single most important feature to differentiate benign from malignant tumor is METASTASIS.
76.  Carcinomas mostly use lymphatic routes and sarcomas mostly use hematogenous routes of spread.
77.  Four types of genes are normally working in human body: a) proto-oncogens b) antioncogenes, c) apoptotic genes and d)DNA repair genes
78.  Proto-oncogenes are changed to oncogenes by three processes: mutation, translocation and amplification.
79.  Major oncogenes are; RAS, ERB-B1, RET, KIT, ABL, C-MYC & N-MYC.
80. Major antioncogenes are: RB, TP53, W.-1, NF-1, BRCA-1, APC.
81. Oncogenic viruses include; Human Papilloma virus, Hepatitis B virus, Epstein Barr virus ,Kaposi Sarcoma Herpes viruses & Human T-Cell leukemia virus (The only oncogenic RNA virus).
82.  Chemical carcinogenesis is a multistep process, divided into initiation and promotion phases.
83.  Major chemical carcinogens associated as include: Asbestos with Mesothelioma, Aniline dyes with TCC, Nitrates-Gastric carcinoma, Aflatoxin with HCC, Vinyl chloride with Angiosarcoma Liver.
84. Radiation induced malignancies include leukemias and papillary carcinoma thyroid.
85.  Major paraneoplastic synbdromes include, Cushing syndrome, ADH secretion by small cell carcinoma lung, Hypercalcemia by Squamous cell carcinoma lung, hypoglycemia by Fibrosarcoma and HCC, Polycythemia by RCC and hypertrophia osteoarthropathy by CA lung.
86. Major tumor markers included : HCG for Choriocarcinoma, calcitonin for medullary carcinoma thyroid, alpha fetoprotein-HCC and  Non-seminomatous germ cell tumor testis, CEA-CA colon, PAP For CA prostate, CA-125 for Ovarian CA , Ca 19-9 for CA Colon and pancreas ,CA 15-3 for CA breast.
87.  Major immunomarkers for epithelial tumors are cytokeratin, for mesenchymal tumor – vimentin, for leukocyte origin tumor – leukocyte common antigen, S100 for neural origin tumors and for skeletal muscle tumors – desmin.
88.  Type I hypersensitivity (“anaphylactic”) or “immediate hypersensitivity”) is the result of antigen binding to IgE on the surface of mast cells and basophils. These instantly degranulate and release active substances into the surrounding tissue.
89.  Type II cytotoxic hypersensitivity, antibodies attach to antigens on the surfaces of a cell and then something injures or destroys the cell.
90.  In type III immune-complex hypersensitivity reaction, “Soluble antigens” precipitate with antibodies, usually this happens 2-4 hours after exposure. This sort of tissue injury is mediated by antigen-antibody complexes (“immune complexes”).
91.  Type IV Hypersensitivity reaction is called “delayed hypersensitivity”. It is mediated by sensitized CD4+T lymphocytes which process antigens in association with class II HLA molecules and release lymphokines.
92.  Immune reactions are divided into two broad categories: A) Humoral immunity-B-cell lymphocyte mediated via production of antibody and Often develops as a response to soluble antigens, and B) Cellular immunity-T-Cell lymphocyte mediated. CD4+helper lymphocytes: help B cells make antibody and also help to generate cytotoxic T cells.
93.  Major histocompatibility complex is present on all nucleated cells.
94.  The HLA system is a key factor in most Transplant rejection reactions. Reactions are mediated by either T lymphocytes or by antibody.
95. Toll like receptors are membrane proteins that recognize a variety of microbe derived molecules and stimulate innate immune responses against the microbes.
96.  CD4 molecule is a high affinity receptor for HIV
97.  Major autoimmune disease include Hashimoto’s thyroiditis, Rheumatoid Arthritis, Sjogren’s syndrome, ankylosing spondylitis.
98.  Gamma interferon is one of the cytokine to activate macrophages and also play major Role in Granuloma formation.
99.  Cytokines are mediators released from one cell and modulate the actions of another cell.
100.  Squamous cell carcinoma is characterized by sheets, groups and clusters of pleomorphic malignant epithelial cells with high N/C ratio,hyperchromatic nuclei and pale cytoplasm.Keratin epithelial pearls,intercellular bridges and individual cell keratinization are seen.
101.  Adenocarcinoma is characterized by back to back closely packed glands lined by pleomorphic malignant epithelial cells with high N/C ratio,hyperchromatic nuclei and eosinophilic cytoplasm.Wall sharing is often noted.
102. Two types of vaccines include: Live vaccines; Measles, Mumps, Rubella, Varicella, Polio etc and Killed vaccines: Rabies, Polio, Hepatitis A.
103.  Protooncogenes are converted into oncogenes.
104.  p53 works by DNA repair and promoting apoptosis.
105.  RB gene activates and Works in hypophosphorylated form.
106. RAS gene protooncogene protein is GTP bound and Works with GAP in cooridination with GTPase.
107.  Gliomas and BCC are highly malignant but dont usually metastasize.
108. AFB is acid fase bacillus ( Mycobacterium tuberculosis ) and called so because it resists decolourization by Concentrated Acids.
109.  Tigered lipid effect is seen in Herat.
110.  Major complement proteins include :
111. Opsonization by C3b
112. Chemotaxis by C5a
113. Anaphylatoxin C3a, C4a, C5a
114. Membrane breakdown and killing C5b,6,7,8,9 MAC complex
115. Enhancement of antibody production C3b
116. FNAC and biopsy are key investigations to early diagnose a tumor.
117. Active Immunity is the resistance induced after contact with foreign antigens eg microorganisms, immunization with live or killed infectious agents, exposure to microbial products (toxins, toxoids)
118. Passive immunity is resistance based on antibodies preformed in another host eg administration of antibody against tetanus, botulism, diphtheria, rabies etc.
119. Sudden death is majorly linked with embolism.
120. 24 to 48 hours post acute inflammation ,monocytes start accumulating.
121.  ubiquitin proteosome pathway & autophagic vacuoles are mainly involved in atrophy.
122. Reserve stem cells are main players in metaplasia.
123. Mechanical and trophic factors are involved in hypertophy.
124. Eosinophils are players in allergic infections.
125. Sequence of events in acute inflammation is :
126. Transient asoconstriction,vasodilation stasis, margination, rolling, adhesion, diapedesis, chemotaxis and phagocytosis.
127. Macrophages seen as a part of reticuloendothelial system include:
128. Osteoclasts – bone,microglia – brain,kupffer cells – liver,alveolar macrophages – lung.Sinus histiocytes – lymph nodes.
129. Tuberculosis is the leading cause of granuloma in Pakistan.
130. Major granulomatous causes include: sarcoidosis, leprosy, cat scratch disease, fungal infections.
131. Grading of a tumor is based on differentiation,atypia and mitoses.
132. Staging of a tumor is based on TNM – tumor,nodes,metastasis.
133. Major autosomal dominant disorders include: Skeletal – Marfan; syndrome, Nervous – Huntington disease,neurofibromatosis, Gastrointestinal – familial polyposis coli, Urinary – polycystic kidney disease, Haematopoietic – hereditary spherocytosis
134. Major intracellular accumulations are :Melanin – melanoma,bile – cholestasis,carbon – anthracosis,copper – Wilson disease, lipofuscin – aging
135. Fatty change is also known as steatosis.
136.   Point mutations are often caused by chemicals or malfunction of DNA replication,  exchange a single nucleotide for another e.g RAS.
137.  Giant cells are cells containing more than one nucleus.
138.  Major giant cells are : Langhan giant cells – Tuberculosis,Tuton giant cells – xanthoma Warthin finkeldey giant cells – measles,Reed Sternberg cells – Hodgkin Lymphoma, Foreign body giant cells – foreign body.
139. IgG fixes complement and crosses placenta.
140. IgM is the most heavy antibody.
141. IgE is the allergic reaction player antibody.
142. Ig A is found in secretions.
143. ABL gene is seen translocated in CML.
144. Lines of Zahn confirms a thrombus.They are alternate layers of platelets with fibrin and RBCs’
145.  Psamomma bodies are lamellated bodies of dystrophic calcification seen in meningioma,papillary carcinoma thyroid and serous ovarian malignant tumors.
146.  Nuclear changes in a necrotic cell include: pyknosis, karyolysis, karryorrhexis and loss of nucleus.
147.  Macrophages get accumulated in chronic inflammation by continuous recruitment,proliferation and immobilization.
148.  Ischemic injury leads to coagulative necrosis.
149.  Major sensitive cell components:  maintenance of integrity of cell membrane, aerobic respiration, protein synthesis, genetic integrity
150.  Liquefactive necrosis: Usually caused by focal bacterial infections, because they can attract polymorphonuclear leukocytes.
151. Coagulative necrosis is characterised by the preservation of cellular and tissue architecture
152. Fat Necrosis: A term for necrosis in fat, caused either by release of pancreatic enzymes from pancreas or gut (enzymic fat necrosis) or by trauma to fat, either by a physical blow or by surgery (traumatic fat necrosis).
153. Caseous necrosis – cheese like : A distinct form of coagulative necrosis seen in mycobacterial infections (e.g., tuberculosis), or in tumor necrosis, in which the coagulated tissue no longer resembles the cells, but is in chunks of unrecognizable debris
154. Gangrene ("gangrenous necrosis") is not a separate kind of necrosis at all, but a term for necrosis that is advanced and visible grossly with super added putrefaction.
155.  Fibrinoid necrosis occurs in the wall of blood vessels when endothelium and smooth muscle cells are injured and dying.
156.  Unlike necrosis, where the cell dies by swelling and bursting its content in the area, which causes an inflammatory response, apoptosis is a very clean and controlled process where the content of the cell is kept strictly within the cell membrane as it is degraded.
157. The extrinsic pathway of apoptosis is initiated through the stimulation of the transmembrane death receptors, such as the Fas receptors, located on the cell membrane.
158. In contrast, the intrinsic pathway of apoptosis is initiated through the release of 
159. In males bronchogenic carcinoma and in females breast carcinoma are at the top.
160.  Preneoplastic conditions include: Cirrhosis of liver, Atypical hyperplasia of endometrium, Leukoplakia, Inflammatory bowel disease, Adenomatous colonic polyps
161. Initiator chemicals -  Cause irreversible damage to DNA, but at maximum they can cause severe dysplasia.
162. Promoter chemicals  itself cannot induce cancer,they propagate or enhance the effects of initiators
163.  Known chemical carcinogens include :A- Asbestos - Lung, mesothelioma. GI tract (esophagus, stomach, large intestine)b- Arsenic - Lung, skin, hemangiosarcomac- Beryllium - Lung d- Cadmium - prostate e. Benzene - Leukemia
164. Ionizing radiation  leads to  dysjunction à random fusion à mutation.
165. Exposure long term of radiations lead to leukemia and thyroid cancers.
166.  Initiation, Latent stage, Promotion and Malignant transformation are recognizable stages in carcinogenesis.
167. Mast cells are the main source of histamine and platelets the main source of serotonin.
168.  Thromboxane A2 (TXA2), from platelets, aggregates platelets, constricts blood vessels. Great for hemostasis.
169. Prostacyclin (PGI2), from the vessel wall, prevents platelet aggregation, dilates vessels. Great for whenever hemostasis is unnecessary.
170. Suppurative or purulent inflammation is characterized by the production of large amounts of pus or purulent exudate consisting of neutrophils, necrotic cells, and edema fluid.
171. An ulcer is a local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflammatory necrotic tissue
172. Teratoma is a tumor derived from more than one germ cell layer.
173.  Seminomas,Melanomas,Hepatomas are malignant tumors.
174.  Extent to which the tumor cell resemble its parent cell is differentiation.
175.  Ranges of differentiation include: well, moderately, poorly, undifferentiated (anaplasia).
176. A malignant cells shows: high N/C ratio,hyperchromatic nuclei, prominent nucleoli, scanty cytoplasm and pleomorphism.
177.  Carcinoma in situ is : Full-thickness dysplasia extending from the basement membrane to the surface of the epithelium.
178. Dysplasia :Atypical proliferation of cells characterized by nuclear enlargement and failure of differentiation which falls short of malignancy
179. The change that occurs in the stroma as tumor invades is called desmoplasia
180.  Benign tumors never locally invade and Malignant tumors always invade the surrounding tissues.
181. Carcinoma of the ovary spreads through seeding of body cavities.
182.  Commonest places for mets deposits are liver and lungs.
183. Perineural spread is seen by carcinoma of prostate and pancreas (2 P’s ).
184.  Nuclear damage is the hall mark of irreversible cell injury.
185. Scientific study of structural changes and functional consequences of injurious stimuli on cells, tissues and organs is Pathology.
186. Metaplasia is a two edges sword because it can lead to dysplasia and the original function of cells is lost.
187. Metaplasia can lead to dysplasia.
188.  ALTHOUGH ATROPHIC CELLS MAY HAVE DIMINISHED FUNCTION,THEY R NOT DEAD.
189.  Pathologic hyperplasia constitutes a fertile soil in which cancerous proliferation may eventually arise like bph and endometrial hyperplasia.
190.  Dysplasia can regress and does not always lead to cancer.
191.  Transudates are fluid accumulations that are essentially salt-water, accumulated because of pressure problems. Exudates are protein-rich fluid accumulations, due to leaky vessels.
192.  In disseminated intravascular coagulation, the clotting cascades are activated throughout the body. This is bad, since it tends to shut down organs due to microthrombi, and also causes bleeding due to consumption of clotting factors and activation of plasmin.
193. Some people reserve the word "thrombus" for the ante-mortem kind, and call post-mortem thrombi "clots".
194.  Arterial thrombi usually occur over ruptured atherosclerotic plaques, less often at sites of other vascular disease or old surgery.
195.  Vegetations are thrombi that occur on cardiac valves. They may be loaded with bacteria ("bacterial endocarditis"), or sterile ("marantic", "verrucous", "bland"; also the thrombi of acute rheumatic fever).
196.  Embolus" comes from the Greek for "bottle stopper".
197. Pulmonary embolization is one of the great killers of hospitalized patients, and that ante-mortem diagnosis is notoriously unsatisfactory even today.
198.  A paradoxical embolus (* crossed embolus) is one from the systemic veins that passes through a right-to-left intracardiac shunt (i.e., a birth defect), to occlude a systemic artery.
199.  Long bone fractures are the main cause of fat embolism.
200. Tumor emboli are bits of cancer that invaded a vein and then broke off. Renal cell carcinoma is famous for this.
201. White infarcts ("anemic infarcts", from "an-", not, and "-eme", blood) are usual when arteries are occluded in solid organs
202. Red infarcts ("hemorrhagic infarcts", sounds like an oxymoron but isn't) result when veins are occluded, or when arteries are occluded in loose tissues (bowel) or with a dual blood supply, or when the organ was already very congested.
203. Monocytes are the largest cells in blood stream.
204.  Histiocytes are mature tissue macrophages.
205.  Cell membrane damage is the first sign of irreversible cell injury.
206.  Lysosomal leakage confirms irreversible cell injury.
207.  Choristomas and hemartomas are not neoplasms.
208. FGF,TGF,VEGF,EGF are main growth factors.
209.  Endothelium gets leaky in acute inflammation due to: 1) formation of endothelial gaps in venules 2) cytoskeletal reorganization 3) increased transcytosis 4) direct endothelial injury 5) leukocyte dependent injury 6) delayed prolonged leakage 7) leakage from new blood vessels

Wound Healing

Three types of wound healing.

(1)        Primary intention (primary union)

•     Wounds that are closed surgically
•     Little tissue loss
•     Skin edges are close together and minimal scarring
•    Healing begins during the inflammatory phase

(2)        Secondary intention (granulation)

• Healing occurs when skin edges are not close together (approximated) or when pus has formed
• If wound is producing or containing pus (purulent) a drainage system is established or the wound is packed with gauze
• Slowly the necrotized tissue decomposes and escapes
• The cavity begins to fill with soft, pink, fleshy projections consisting of capillaries surrounded by fibrous collagen (granulation tissue)
• The amount of granulation tissue required depends on the size of the wound
• Scarring is greater in a large wound

(3)        Tertiary (third) intention

•  Delayed primary closer
•  Two layers of granulation tissue are sutured together
•  Occurs when:   Contaminated wound is left open and sutured closed after the infection is controlled  Delayed suturing of a wound.   Primary wound becomes infected, is opened, is allowed to granulate, and is then sutured.
• Results in a larger and deeper scar than primary or secondary intention

Factors promoting wound healing

(1)        Adequate oxygenation

(2)        Adequate rest or local immobilization

(3)        Sufficient blood supply

(4)        Proper nutrition

(a)        Nutrients are needed for wound repair and prevention of infection

(b)        Adequate wound healing is dependent upon the availability of essential nutrients

Factors that impair wound healing

(1)        Age - causes slower regeneration of tissue

      Physiological Effects

(1)        Alters all phases of wound healing

(2)        Vascular changes impair circulation to wound site

(3)        Reduced liver function alters synthesis of clotting factors

(4)        Formation of antibodies and lymphocytes is reduced

(5)        Collagen tissue is less pliable

(6)        Scar tissue is less elastic

       Interventions

(1)        Instruct patient on safety precautions to avoid injuries

(2)        Be prepared to provide wound care for longer period

(3)        Teach home caregivers wound care techniques

(2)     Malnutrition

       Physiological Effects

(1)        All phases of wound healing are impaired

(2)        Stress from burns or severe trauma increases nutritional requirements

      Interventions -  Provide balanced diet rich in protein, carbohydrates, lipids, vitamins A and C, and minerals

(3)       Obesity

       Physiological Effects -  Fatty tissue lacks adequate blood supply to resist bacterial infection and deliver nutrients and cellular elements

       Interventions - Observe obese patient for signs of wound infection, dehiscence, and evisceration

(4)       Impaired oxygenation

        Physiological Effects

(1)        Low arterial oxygen tension alters synthesis of collagen and formation of epithelial cells

(2)        If local circulating blood flow is poor, tissues fail to receive needed oxygen

(3)        Decreased hemoglobin (anemia) reduces arterial oxygen levels in capillaries and interferes with tissue repair

        Interventions

(1)        Diet adequate in iron

(2)        Monitor patients’ hemotocrit and hemoglobin levels

(5)        Smoking

        Physiological Effects

(1)        Reduces the amount of functional hemoglobin in blood, thus decreasing tissue oxygenation

(2)        May increase platelet aggregation and cause hypercoagulability

(3)        Interferes with normal cellular mechanisms that promote release of oxygen to tissue

        Interventions -  Discourage patient from smoking by explaining its effects on wound healing

 (6)       Presence of infection

 (7)       Drugs

      Physiological Effects

(1)        Steroids reduce inflammatory response

(2)        Anti-inflammatory drugs suppress protein synthesis, wound contraction, epithelialization, and inflammation

(3)        Prolonged antibiotic use may increase risk of superinfection

(4)        Chemotherapeutic drugs can depress bone marrow function, number of leukocytes, and inflammatory response

        Interventions  - Carefully observe patient; signs of inflammation may not be obvious

(8)        Diabetes mellitus

       Physiological Effects

(1)        Causes small blood vessel disease that impairs tissue perfusion

(2)        Causes hemoglobin to have greater affinity for oxygen, so it fails to release oxygen to tissues

(3)        Alters ability of leukocytes to perform phagocytosis and also supports overgrowth of fungal and yeast infection

        Interventions

(1)        Instruct patient to take preventive measures to avoid cuts or breaks in skin

(2)        Provide preventive foot care

(3)        Control blood sugar to reduce the physiological changes associated with diabetes