Download Notes for Pathology Final at Winter 2002

Notes for Pathology Final at Winter 2002
SHOCK:
Circulatory shock – blood impairment at micro-circulatory level (state of imbalance
between supply of blood to tissue and amt of nutrients to meet metabolic needs)
- microcirculation depends on blood hydrostatic pressure and deals w/
arterioles-capillaries-venules
- hydrostatic pressure depends on two factors
o cardiac output - depends on heart contractility and heart rate
o peripheral resistance – depends on state of sphincter of precapillary
arteriole
 TPR also depends on:
 symp nerve – vasoconstriction
 epinephrine/norepinephrine – vasoconstriction
 angiotensin II – most powerful vasoconstriction
 (no parasymp influence, no vasodilation )
 (decrease symp, get vasodilate)
Primary shock aka Neurogenic shock, syncope (sudden loss of consciousness), fainting
-Developes when:  BP,  cebreal blood flow, and loss of consciousness
(because blood falls to feet)
-Due to: emotional stress sever (or severe pain)
-Results in: altered info to cord, loss of consciousness interrupts emotion and
vascular relationship so can restore normal blood circulation or can take
barbiturates which inhibits cerebral cortex
Secondary shock – 3 types
1. Cardiogenic shock –  CO   perfusion (circ of fluid thru tissues ie blood)
-Due to: heart malfxn:  HT contraction due to: pumping restriction,
impaired venous return, myocardial weakness, or arrhythmias
-Results in: cardiomyopathies ( myo strength), MI, arrhythmias,
thrombosis in HT channel, atrial/ventricular opening, venous return
thrombosis propagation (IVC to RA to RV to pulm opening = obstruction)
2. Hypovolemic shock – Normal CO,  volume,  perfusion
a. Due to:
i. lg vessel damage, hidden vessel damage (peptic ulcer, bleeding
hemorrhage, extrauterine pregnancy and related rupture of
vessel w/ abdominal hemorrhage)
ii. third degree burns where 15% of body damaged (burns expose
vessels  evaporation of fluid  inflammation and  fluid 
tissue loss of plasma and protein that escape to burn surface 
osmotic pressure from blood to exposed tissue  shock)
iii. cholera  diarrhea  fluid loss or profuse vomiting (w/
pregnancy)  fluid loss
iv. hypertrophic pylorus stenosis – in newborn, is the inability of
food absorption in duodenum  severe vomiting  fluid loss
1
3. Vascular shock – Normal CO,  perfusion ; Due tovascular lumen too big due
to widespread dilation of systemic arterioles
a. Septic shock : bacterial toxins cause inflammation and vasodilation
b. Toxic shock : associated with non-bacterial toxins that vasodilate
c. Anaphylactic shock : rxn between antigen/antibody  massive
vasodilation due to histamine release (allergic rxn)
HYPERTENSION: when BP  140/90
-hi nomal: systolic 130-135, diastolic 85-89
-affects 25% of world population, 95% of 1 and 2 hypertensions are benign and
controllable
A. Primary (essential) hypertension – 90-95% undergo full recover if problem
removed (chiropractic can help)
B. Secondary hypertension – 5% leads to MI and stroke (and death) w/in 1-2
years because are malignant and cannot be controlled thru any means
BLOOD VOLUME REGULATION:
Humoral factors: constrictors
(angiotensin II,
catecholamines,
Blood volume: Na,
thromboxane, leukotrines,
mineralocorticoids,
endothelian) and dilators
atriopeptin(prevents
(prostaglandins)
reabsorption of Na)

BP
=
CO

Cardiac factors:
HR, contractility

x
TPR 

Local factors:
autoregulation
and CO2
Neural factors: 
(dilators) and 
(constrictors) adrenergic
receptors
BLOOD PRESSURE REGULATION:
A. primary regulator = kidney and requires spec BP for normal filtration in
glomerulus.  BP stimulates renin secretion which is produced in
juxtaglomerular cells peri afferent arterioles
B. Renin in blood circulation  cascade angiotensinogen  angiotensin I
travels to lung  angiotensin II (powerful vasoconstrictor)  directly:
contracts smooth muscle of arterioles and indirectly: increased aldosterone
from adrenal cortex  increased blood volume
THEORIES OF HYPERTENSION:
A. Genetic – increased Na leads to hypertension ( ECF,  CO)
B. TPR – fxnal vasoconstriction   vascular sensitivity and  TPR and
hypertension
C. Vascular smooth muscle defects (growth and structure of lumens) – narrow
lumens, increased wall thickness leads to hypertension
2
NUTRIONAL DISORDERS:
I. Vitamins: All vitamins except B2 have nerve system involvment
A. Fat Soluble: ADEK
a. Vit A
i. maintain normal vision in reduced light, makes rhodopsin
(accepts light in rods via iodopsies which are 3 main
colors/pigments of cones)
ii. potentiating the differentation of specialized epithelial cells,
mainly mucous secreting
1. deficiencies lead to:
a. keratinization of: cornea, bronchial wall, kidney
stones, nidus (“nest” of epithelial cells
precipitating calcification of renal pelvis or
bladder)
b. xerophthalmia (dry cornea and conjunctiva) 
Bitot’s spots (debris of epithelial cells)
c. Keratomalacia – softening of corneal epithelia
leading to ulcerations of cornea and to blindness
iii. enhancement of immunity to infection
1. deficiencies lead to:
a. infectious diarrhea, pneumonia, measles, and
death
b. congenital def: increased IC pressure
(vomiting and stupor); hyperkeratosis (of skin);
damage of LV (megaly)
b. Vit D
c. Vit E – alpha tocopherals
i. Scavenger of free radicals (stabilize esp cell membrane)
(nervous system most vulnerable if fat metabolism is impaired,
there is interference w/ ADEK absorption)
1. Deficiencies lead to:
a. Problems w/ neural axon membranes – degen of
axons in post column, loss of DRG cells, myelin
degen of sensory nerves, and degen of
spinocerebellar tract  ataxic gait and
decreased sense of position, vibration, pain
perception
b. RBC membranes  anemia
d. Vit K
i. Coagulation rxn – formation of clotting factors, development
of prothrombin (precursor to thrombin) which converts
fibrogen to fibrin
ii. Promotes calcification of bone
3
iii. Deficiencies:
1. Hemorrhagic disease of newborn – due to maternal lack
of vit K, in infant results in intracerebellar hemorrhage
of subarachnoid space and stroke
2. Pregnant women may hemorrhage during birth
B. Water Soluble vitamins:
a. Thiamin = B1 , fxn = neural membrane , neural conduction
i. Deficiencies:
1. hypothiamin – chronic alcoholics, polished rice (poor in
Asia), pregnancy, diarrhea
2. Beriberi - degen NS, demyelinate long axons
a. Dry beriberi – degen and demyel  neuron
conduction impairment, decreased reflex arc
response, extremity drop manifestation
b. Wet beriberi – cardiovascular: vasodilation 
inc arterial-venous shunt  inc heart load
hypertrophy of 4 HT chambers  heart muscle
thinning  failure
c. Wernicke-korakoff syndrome
i. Wernicke encephalopathy
1. opthamoplasia – abnormal eye
mvmt
2. nystagmis
3. ataxia
4. disorientation
ii. Corscophycosis - retrograde amnesia
b. Niacin = B3 aka Nicotinic acid (syn from tryptophan in body)
i. Deficiencies: Pellegra = skin roughness, 4D’s, discovered by
Joseph Goldburger in prisons w/ prisoner diets
1. Dermatitis – sun exposed areas, “Casel’s necklace”
around neck
2. Diarrhea
3. Dementia – weakness, dizziness, degen of cord 
paralysis, may be irreversible
4. Death
c. Riboflavin = B2 – upper GI tract absorption
i. Deficiencies:
1. Cheilosis – at angle of mouth and pallor, cracking
infection
2. Glossitis – severe atrophy of tongue
3. Superficial interstitial keratitis – growth of vessels into
cornea, ulcerations of corneascar tissueblindness
4. Dermatitis – in face, groin at labial folds(butterfly look)
4
d. Pyrydoxine = B6 (cooking destroys this)
ii. Same pathway as B2
iii. Deficiencies:
1. uncommon; drug use may cause and seen w/ alcholics
2. when do occur, result in: glossitis, seborrheic
dermatitis, keratosis
d. Cobalamine = B12
i. Fxn – diet and microflora of gut
ii. Absorption: B12 bound to proteinstomachpepsin
separates B12 and proteinB12 binds to R binder of
salivaduodenumseparation of B12 and R binderB12
binds to IFblood
iii. Deficiencies
1. B12 not bound to R binder will destroy ST and epi
cellsno IF bindingno blood absorption
2. Pernicious anemiano production of RBC’s, WBC’s
platelets
3. CNS pathology – myel degen of post column
e. Vit C = ascorbic acid
i. Fxn: promotes procollagen formation, scavenger of free
radicals, decreased prod of LDLP, cannot be syn in body
ii. Deficiencies:
1. scurvy
a. inc permeability of vesselshemorrhages and
petechiae
b. skeletal changespectus excavatum, leg bows
c. gingivitis due to non stable alveoli
d. subperiosteal hemorrhages
e. cartilage degenrheumatoid arthritis
f. retrobulbar hemorrhageblindness
g. subarachnoid hemorrhagedeath
h. improper wound healingscar tissue can’t
close wound
PROTEIN MALNUTRITION:
General notes
- 25% of children in 3rd world countries due to inadequate dietary intake
- somatic protein compartment – skeletal muscle
- visceral protein compartment – in visceral organs, mostly liver
Marasmus (wasting)
- loss of skeletal muscle mass, head appears abnormally big
- listlessness, death
Kwashiorkor (first,second)
- improper source of proteins
- baby taken off breast and lose protein intake
- decrease of visceral protein compartment and blood protein (albumin)
- face and belly swelling
5
Reversible Tissue Formation:
Neoplasia:
- Tissue formation and involves the overgrowth of a tissue to from
neoplastic mass , of neoplasm which is called a tumor.
- most common killer in US of people under 15 yrs old, widespread abnormality,
no limit to cell growth
Hypertrophy: Is the process of cell and organ enlargement that occurs in response to
increased demands
- reversible
Regeneration: healing from wounds
Hyperplasia: increased mitosis produces new cells but only in quantities needed to meet a
particular demand
- reversible
Metaplasia: Is a change of the cell type
- less reversible
- more serious than hyperplasia.
Dysplasia: Is a loss in the uniformity of the individual cells as well as a loss in their
architectural orientation
- less reversible
- if all cells change  neoplasia, uncontrolled tissue growth
- assoc w/: Pleormorphism - is characterized by: variability of the cell size/shape
and larger, darker nuclei in contrast to the regularity of the cell structure seen in
normal tissue
Aplasia: lack of organ development
- not reversible
Hypoplasia: inadequate development, so that the resulting structure is immature and
functionally deficient.
- not reversible
I.
ONCOLOGY: the study of Neoplasia
a. Benign
b. Malignant – crab appearance due to invasive nature
c. Two characters of tumors
1. Pattern growth:
Benign tumor
Grow relatively slow
Growth is orderly
Tumor remains localized
Malignant tumor
More rapid growth
Disordered growth
Aggressive invasion into
normal tissue
2. Tissue of Origin:
A. Benign Tumor - an root word indicating a type of tissue that
has become neoplastic and suffix - oma
Ex: Osteoma (from bone tissue)
Adenoma (from glandular tissue)
6
Malignant tumors *
according to their embryonic origin
*
derived from ectoderm or endoderm 
carcinomas
*
derived from mesoderm’s  sarcomas
*
Ex: fibrosarcoma (from fibrous C.T.)
Chondrosarcoma (from cartilage)
B.
Sound benign but are NOT BENIGN (Note Well for test)



Melanoma (malignant melanoma)
Sound malignant but are NOT MALIGNANT
 Lymphoma (lymphoscarcoma)
 Hepatoma (Hepatocellular carcinoma) Chiro. U.C. adjustment two
people cured!!!
 Basal cell carcinoma (deep layer of the skin)
 Squamous cell carcinoma depends on depth of cancer (deep skin layer
origin)
Structure of tumors:
 Parachymia – neoplastic tissue, does not resemble normal org tissue
 Benign tumor – resemble tissue of origin, almost norm size/shape
 Malignant - least resemblance to normal tissue. (cell differentiate from
the normal cells/ don’t look like normal cells due to high mitotic rate)
 Anaplasia – look likeembryonic cells, lack of differentation or
reverse of normal differentation (the higher the degree of
anaplasia, the more malignant the tumor)
 Stroma - C.T. skeleton ; different degree of tissue saturation of blood
 Tumor factor: increased vascular permeability, increased
nutrients, increased stroma  Scirrhous (e.g. stomach Ca.
Thick walls, no elasticity = leather bottle disease)
Behavior of tumor
 Vascularization –
 Tumor angiogenesis factor – development of vessels for needs of
tumor. Vessels are not stable (b/c have no basement membrane and
have loose endothelial jxns). Prevents tumor from growing too fast,
and causes tumor to explodetumor necrosis
7

Characteristic of Benign and Malignant Tumors:
Characteristic
Cell Structure
Benign
Near Normal
Malignant
Abnormal Shapes,
lg cell and nucleus
Tissue Structure
Orderly
Disordered, Irregular
Growth Rate
Above Normal
Rapid ( mitosis)
Invasive Growth
Uncommon
Typical
Metastasis
Never
Typical
Capsule
Typical
Rare, Incomplete if
present
Anaplasia
Minimal
Typical
Prognosis
Good
Poor
 Malignant and Benign Tumors may overlap = very hard to diagnosis
for doctors
 Tumor invasion (malignant) does the following:
 Sends columnar cells into normal tissue
 Compression/pressure atrophy of normal tissue
 Impairment of blood supply to normal tissue
 Replacement of normal tissue w/ tumor b/c tumor “eats” it for nutrient
 Tumor Cell Motility (malignant):
 reduced adhesiveness and tearing away from main tumor site
 tumor cells digest basement and basal membrane to penetrate tissue
beyond
 chemotaxis – metabolites of normal tissue attract tumor cells for all 3:
 tissue metabolism
 degen of basal and basement membrane
 autocrine motility factor – produced by malig. Cells
 Tumor Metastasis – tumor will go to areas of least resistance
 Areas resistant: Bones, Pleura, Pericardium, Peritoneum, Fascia
 Tumor cells to blood:
 Thin wall of veins more permeable to tumor Embolism gets into
the veins  emboli  tumor breaks down vessel wall to reach
new tissue site
 Tumor cells to lymph (most common):
 Tumor growth within lymph  obstuction of lymph flow 
spread to collateral circulation (narrowing and to other nodes) 
increased metastasis
 goes to the lungs (most common place of metastasis).
 May spread from arteries (from lungs) to kidneys and bones
 Virchow’s nodes - supra clavicular lymph nodes
 Surgery tends to spread cancer = iatrogenic metastasis
 If in abdominal cavity, easy to spread due to so many organs
 Krukenberg tumor = metastasis of stomach cancer to ovaries
8
Primary tumor
Typical site of metastasis
Carcinoma & breast adenocarcinoma=====Bone (vertebral column)
Bronchogenic Carcinoma =============Spinal Cord
Prostrate Carcinoma ================ Bone (especially vertebral column)
Neuroblastoma ==================== Bone
Compression of Soft Tissue:
 Lung Cancer pushes on pericardial space, penetrates and invades the
heart space = Necrosis
 Side note: Adenoma of pituitary gland - compressed the brain
 Tumor compression of ureters - prevent normal urination = compression of all soft
tissue areas = necrosis and death of kidney
Compression of Vessels (very painful):
 Artery able to resist and may change direction
 Vein - weak walls due to decreased pressure in veins  compression of vein
 (benign) tumor directly:
 1 - fills up open spaces or cavity
 2 - act for diff types of infection (decr WBC in circ, decr immune system, decr
infection fighting)
 3 – compromises barriers (like skin)
 4 – effect on blood – loss of blood that accompanies growth of tumor  decr
blood flow  tissue necrosis cavity that can be infected or fill w/ blood/fluid
(can see on x-ray, hemoptosis = 1st sign of tumor = blood in sputum)
 in bone marrow, - decr platelets b/c decr ability to bleed
 in clotting factor – decr w/ liver tumor b/c decr ability to bleed
 in kidney, decr erythroprotein production, incr polycythemia, incr
RBCthrombus formationthrombusdeath
 Sequela of tumor:
 Incr ability to bleed
 Decr clotting ability
 Erythropoesis impaired  anemia
 Less RBC, decr HBG
 Abnormal B12 and Fe absorption (w/ stomach tumor) absence/decr
IF production
 Pain: assoc w/ all tumors
 Cachexia: nearly always assoc w/ tumor: char by typical S&S:
 Generalized muscle weakness
 chronic high fever
 wasting
 anorexia (declined appetite)
 pallor
 liver toxication
 cachectin secreted by tumor (tumor necrosis fator – alpha) decr
weight
9



Treatment of tumor:
 Ionizing ratiation  decr hemopoesis  anemia
 Psychostatic therapy  loss of hair and decr erythrocyte  anemia
Paraneoplastic examples:
 Comn’s syndrome – benign tumor of adrenal cortex incr
aldosterone incr Na absorption incr H20 reabsorption
hypertension
 Pheochromocytoma- benign tumor of adrenal medullaincr
NEvacoconstrictionextreme hypertension
 exotopic secretion - some areas of the body contain neuroendocrine
cells
 Paraneoplastic syndrome- neuroendocrine tumor (in bronchial walls of
lung) produce different hormones
 Paraneoplastic syndrome:
 Tumor of endocrine gland  incr hormone from that gland
 Tumor near “ “  compress gland  atrophy
 Hypertrophic Pulmonary Osteo Arthropathy clubbing of fingers b/c:
 toxic products of tumor in circulation
 formation of antibody/antigen complex starts
immune response (which may be pathological)
 increased bone formation (hyperosteosis) ; accompanies
lung and heart problems (must rule out lung and
esophagus cancer)
 Dermatomyositis- 60% of cases; severe weakness of muscles to
atrophy; people die due to weakness of breathing muscles.
Associated w/ development of tumors:
 Type of tissue
 Heredity:
 Retinoblastoma- children (malignant)
 Polyposis Coli- malignant , multiple polyps
 Xexroderma Pigmentosum- malignant skin tumor
 Environmental Factors:
 Ionizing Radiation- destruction of DNA; improper division of cell;
depression of bone marrow = decreased RBC’s, WBC’s = loss of
ability of the immune system.
 Solar (radiation of the Sun) UV rays; carcinogenesis
 Virus- predisposition to cancer ex. A.I.D.S.- due to decreased immune
response
 Human Papalova Virus- in women 6-7 times in cervical cancer
due to birth control pills (this is due to progesterone)
 Virus
Associated Tumor
 Hepatitis B and C
Hepatocellular Carcinoma
 Human Papilloma Virus (HPV) Skin Cervical Carcinomas
10





 Human T-cell Leukemia Virus Some Leukemia
 Epstein Barr virus
lymphoma
Carcinogens Organic
 Polycyclic Hydrocarbons- Production of organic combustion
ex. Smoking: (benzppyrene) or combustion (paper burning)
 Aromatic Amines - color additive to food; promotes liver,
kidney and bladder cancer
 Nitro Amines- produced by nitrates and AA, these are artificial
preservatives
 Aflatoxin- from aspergillus- fungus on vegetables  liver
cancer
Inorganic Carcinogens- Lead, Cobalt, Cadmium, nickel- Asbestos,
Lung Cancer 5 times more likely to get with smoking, 100 times more
likely to get lung cancer w/ asbestos exposure & smoking
side note: classic way to get cancer
 radiation 2-5%
 smoking 31%
 bad nutrition 29% (2/3 of all cancers are attributed to smoking and poor
nutrition)
IMMUNITY:
Immune Systems (2 parts):
 Non specific “innate” resistance – ability to recognize self/not self
 Anatomical and physical barrier
 Skin (sebaceious glands, sweat glands)
 Mucous membranes – cover all inside and outside body
 Physioligical barriers
 Fever
 Acidity
 Various soluble factors:
 Lysosome – antibacterial, produced by saliva
 Interferon – WBC’s fight virus
 Complement – non spec resistance that activates cascade to kill
intruder
 Phagocytosis – elimination of intruder via:
 Inflammation
 Acquired “specific” immunity – cells of the immune system
 Lymphocytes = T-cells
 T- helper cells (T4) – regulate fxn of immune cells
 T-cytotoxics (T8) – bind to intruder cells:
 1- immune response against tumor cells
 2 – immune response against invader/virus cells
 3 – take part in fight against transplant/grafts
11




T-s suppressors (T8) – suppressor of exaggerated immune reactions

 T-m memory cells - memory of all the antigens that they had all there
entire life. Ex: mumps - will never get again due to these cells.
 T-s supplements (T8) - production of suppressant of immune reactions
 Lymphocytes = B-cells (mature in bone marrow, don’t go to thymus)
 Produce plasma  antibody formation
 Natural Killers: (NK) – neutral and kill intruders
 Antigen presenting cells (APC) – engulf intruder  divide into pieces 
present pieces to immune cells (macrophages, B-Cells, dendritic cells) for
disposal
Innate and Acquired:
 Cytokines – interleukins
 Complement system – group of proteins that undergo activation thru cascade C1C9 components  MAC (Membrance Attack Complex) directly kills intruder
Immunoglobin factors – antibodies
 IgM - primary response of intrusion
 IgG - main class immunoglobulins
 IgE - special class in allergic reactions
 IgA – primary protection of antigen invading GI membrane
 IgD – fxn unclear
Type I hypersensitivity rxn (anaphalactic type) (allergies)
 - there is release of vasoactive amines & other mediators derived from the
permeability and smooth muscle in various organs. Ex. Mast cells
 histamines
 incr permeability of vessels
 vasodilation
 bronchispasm
 incr mucus secretion
 results:
 Sensitization:
 Plasma cells in lymph release IgE
 Mast cells and basophils sensitized by IgE attachment to cell
membrane
 Reexposure to same agent
 Allergic
 Antigen reacts w/ IgE  secretion of pharmacologic
mediators  tissue swelling

Systemic Anaphylaxis Reaction
Local Anaphylaxis Reaction
 Itching, hives
Urticaria (hives)
 Bronchospasm
Hay fever
 Laryngeal Edema
atopic bronchitis asthma
 Vascular Shock
rhinitis

12



Type II hypersensitivity rxn (Antibody Dependent): Humoral antibodies participate
directly in injuring cells by predisposing them to phagocytosis or to lysis
 Complement dependent reactions- Antibody-antigens complex binding on
surface of cells
 Opsinization makes cell attractive for phagocytosis
 F-c (the heavy chain) portion of Ig kicks off complement
 Ex. Hemotransfusion rxn (incorrect blood type, antigens will lyse RBC)
 Ex. Erythroblastosis fetalis aka Reso’s conflict: Rh- found in 85% of
world population, could lead to fetus w/ hemolytic anemia, jaundice and
would need blood transfusion due to antigen binding to fetus RBC’s
 Ex. Autoimmune hemolytic anemia and certain drug rxns: antibodies
develop against RBC’s  anemia
 Antibody dependent cell-mediated cytotoxicity
 No complement participation required here
 Simply attracts the anti-killer and kills the killer
 Ex. Parasites and tumor cells
 Antibody-mediated Cellular Dysfunction:
 Ex. Myasthenia gravis - stopped at the synaptic cleft the antibody goes
into the cuff and blocks the bulb and Ex. Graves’ Disease
Type III hypersensitivity reaction – formation of immune complexes in circulation
with their further disposition into tissues which result in injury of those tissues
 Antibodies formed  meet antigenform complex (free flowing in
blood) attach to vascular wallphagocytosis of complex but result
simultaneously in digestion and inflammation of vascular wallplatelets
activatedmicro-thrombitevasculitisdeat
 Ex. Vasculitis and glomerulonephritis
 Arthus phenomena – local manifestation of type III
Type IV hypersensitivity reaction cell-mediated type: Cell mediated immune
response with sensitized lymphocytes ultimately leads to cellular and tissue injury
 Not assoc w/ humoral agents (antibodies)
 Delayed type hypersensitivity: T4 helpers activate lymphocytes w/ antigen
intrusion  try to restrict antigen w/in body  granuloma formation and giant
cells  specific necrosis (Kaseus necrosis)
 T-cell mediated cytotoxicity: assoc w/ T8 cytotoxic cell participation
 3 phenomena
 antivirus activity
 antitumor activity
 graft rejection ( in organ transplant)
 via T8 mechanism:
 release perforin (makes holes in infected cell)
 produce lymphotoxin (enters cell and results in lysosomes activiation
that are already in cell which digest the cytoplasm)
 releases gamma interferon (activates phagocytosis by attracting
macrophages)
13