exam 1- pathology

Hypoxemic hypoxia

Partial pressure of O2 is not enough to reach the alveoli due to environmental reasons or respiratory disease

ex. pneumonia or high altitudes or pulmonary embolism

Ischemic hypoxia

tissue does not receive enough O2 because of decreased perfusion due to cardiac or vascular disorder

ex. stroke or heart attack

Anemic hypoxia

problem with the O2 carrying capacity of the RBC like anemia + carbon monoxide poisoning + transport issues + lack of hemoglobin

Histoxic Hypoxia

tissue unable to use O2 because it has been poisoned

ex. cyanide poisoning

Dysoxia

inability to make full use of the oxygen available; histotoxic hypoxia is a type of dysoxia

- after less O2, the cells switch to anaerobic resp--> mito can become dysfunctional--> cells will no longer prefer/ use O2 after time

-increased oxygen demand

hyperplasia

inc. cell number

atrophy

decreased cell size

Metaplasia

conversion of once cell type to another

ex. cigarette smoke can turn columnar to simple squamous

hypertrophy

increased cell size

dysplasia

disorderly growth --> tumor/cancer/ neoplasm

Resolution

short time after minorly damaged tissues --> cells returns to normal

Regeneration

occurs in mitotic tissues; dead cells are replaced by neighboring cells = perfect repair

Replacement

Occurs in tissues that cant mitoticly regen (ex. muscle cells); dead cells are replaced with CT (fiber) and forms a scar, loss of function.

4 cardinal signs of Acute inflammation

- redness

-heat

-swelling

-pain

Glucocorticoids in the HPA axis

inhibits the arachidonic acid pathway by inhibiting phospholipase A2 which basically starts it

What type of WBC mainly in AI

Neutrophils

What type of WBC mainly in CI

Monocytes, Macrophages, Lymphocytes

Central lymphoid organs

-Bone marrow

-Thymus

An environment for prod and maturation of immune cells composed of a CT called reticular tissue (?)

Peripheral lymphoid organs

-lymph nodes

-tonsils

-appensix

-peyer's patches

-GI and Reproductive systems

Recognize and process antigens; promote cellular interactions necessary for development of adaptive immune responses

Cell death that does not have CM rupture

Apoptosis--> planned

-usage of macrophages / phages--> no inflammation

-intrinsic and extrinsic pathway

Cell death that CM does rupture

necrosis

-can occur due to unregulated enzymatic digestion of cell components, loss of CM integrity, lysosome eruption, high levels of Ca2+ and lysing of cells

Can be induced by ;

-ischemia

-infection

-trauma

-toxins

Cellular senescence

inability of cell to divide due to aging

Aging and its effect on cells

-telomere shortening

-less resistant to ROS--> free radical injury

-Apoptosis

-impaired protein homeostasis

-defective nutrient sensing

-accumulation of damaged DNA

-deterioration of integrity and structure of nucleus

Which cell can co-stimulate T-cytotoxic cells and B cells

Lymphocytes T-helper cells

Symptoms of anaphalactic shock

-Vascular shock

-Widespread Edema

-difficulty breathing

- swelling

-redness

-weak pulse

-decreased blood pressure --> will kill u

Latex gloves can induce ______ hypersensitivity

Type 4

Feature of malignant cells

poorly differentiated or has a wide range of cellular changes

What changes in client's cells have occurred to allow metastasis

- cytoskeleton lose fibronectin and cellular matrix ( cytoskel) they become more amenable to proliferation

TNM characters used in staging system

T- primary tumor

___X - cannot be evaluated

___0-- no evidence of

--is -->carcinoma in site but not spread

__1

__2

__3-->size or extent of primary tumor

Regional Lymph nodes (N)

x- cant be eval

0-no regional lymph node spread

1-2-3 -->involvement of regional lymph nodes + number and extent

M- Metastasis of cancer cells

Potential chronic side effects of chemo

cardiotoxicity--> occurrence of heart electrophysiology dysfunction or muscle damage

+Loss of skeletal muscle mass

Hematologic cancers

arising from abnormal cells in hematopoetic system --> varies according to specific cell line of origin

Hematopoesis

formation of blood cellular components

Leukemia

Malignancies originating in bone marrow or blood

Lymphoma

Malignancies originating in lymphatic tissues

Classifications of Leukemia

Myelogenous

Lymphocytic

Acute

Chronic

Myelogenous

Neoplastic (cancerous) changes in myeloid cell line

Lymphocytic

Neoplastic changes in lymphoid cell line

Acute leukemia

blocks in precursor hematopoeitic cells

Chronic leukemia

Block in later stages of maturation and differentiation of hematopoietic cells

Leukemia vs normal blood cells

higher number of WBCs

4 major types of leukemia

Acute Myelogenous leukemia (AML)

Acute lymphocytic leukemia (ALL)

Chronic Myelogenous leukemia (CML)

Chronic lymphocytic leukemia (CLL)

WBC disorder related concepts

- unregulated proliferation of WBC

-Can be caused of environmental influences or genetics

-Proliferation of malignant cells disrupts prod. of RBCs, neutrophils, thrombocytes (platelets)= thrombocytpenia

Acute myelogenous leukemia accounts for ______ of all new cases of leukemia

30%

AML has an increased incidence in populations of ______________

60 or 60+ years old

Risk factors for AML

-Chemotherapy- from different cancer treatment

-ionizing radiation

-long term exposure to toxins

-smoking

AML is a result of

series of genetic mutations in hemopoietic precursor cells; this leads to :

-abnormal and immature hematopoietic cells

- accumulate in bone marrow and peripheral blood

- crowd out other hematopoietic cells = decrease in immunologic system

-pancytopenia

Proto-oncogenes vs oncogenes

proto-oncogenes--> normal genes that stimulate cell division and proliferation

* opposite of *

Oncogenes--> mutated normal genes that allow cels to proliferate unregulated

Pancytopenia

- result of AML

Condition where there is a decrease in all three: EBCs, WBCs (leukocytes: non-macrophages or neutrophils) and platelets

This leads to:

-anemia

-infections

-bleeding

-infiltration of other tissues

Clinical manifestations of AML

-pancytopenia

- ineffective hematopoietic cells + overcrowded hematopoietic system

-weakness+ fatigue due to anemia

-pneumonia

-upper respiratory infections

-urinary tract infections

-bleeding due to thrombocytopenia

-leukocytosis ( too many)

Treatment for AML

-restore normal hematopoeisis

-systemic chemotherapy (typically the pts. are so old that the treatment may kill the pt before it kills the cancer)

Acute lymphocytic leukemia makes up _______ of new cases of leukemia

12%

ALL typically affects children anyways, but who has better prognosis- children or adults

children

5 yr survival rate for children and adults for ALL

children: 90% Adults: 40%

if ALL is IDed before 1 yr old or past 10 yrs old = very bad or good

Bad

"blasts"

abnormal leukemia cells

Risk factors for ALL

Nongenetic:

-prenatal exposure to x-rays

-postnatal exposure to high doses of radiation

Pathogenesis for Acute lymphocytic leukemia

-clonal disease

-ineffective lymphoid cells

-overcrowding of bone marrow

-infiltration of leukemic cells into other orfans

Clinical manifestations of ALL

-infections that never goes away

-non specific early:

-constant fever, bleeding, bone pain, lymphodenopathy (swelling of lymph nodes)

-Bone pain

-enlarged lymph nodes

-CNS involvement --> head pains (uncommon)

Diagnosis for ALL

Assess for signs of :

-infection, leukemic infiltration, anemia, over bleeding, tissue diagnosis for classifying leukemia

Treatment for ALL

eradicate malignant immature lymphoid cells + chemotherapy

CML more common in _______

Adults; median age @ diagnosis= 64 yrs

Classifications of CML is based on how many dysfunctional cells you have; what are the 3 phases called?

Chronic

Accelerated

Blastic

Chronic phase of CML

blast (abnormal leukocytes) <10%

Accelerated phase of CML

blast cells 10-19%

Blastic phase

blast cells > 20%

Cause of CML

9;22 translocation (philadelphia chromosome)

Clinical manifestations of CML

-asymptomatic @ diagnosis

-depends on degree of overproduction of myeloid cells

-infection related to neutropenia

-lack of neutrophils/first line of defence=longer inflammations

-weakness + dizzyness =anemia

-bleeding bc of thrombocytopenia

Others:

-night sweats or excessive sweat

-splenomegaly --> enlargement of spleen

-Gouty arthritis--> common in leukemia

Diagnostic process of CML

-ID of CML phase

Poor prognosis factors of CML

-older age

-symptoms present @ diagnosis

-Significant weight loss

-hepatomegaly and splenomegaly

Why does the liver and spleen enlarge in CML? why not kidney too?

they take care of platelets, lymphocytes, RBCs, leukocytes while kidneys just does plasma

The most common type of leukemia is

CLL

what population is CLL common in

Older adults; inc. incidece in ppl over 50yrs old

What system of classification do we use for CLL in the USA

Rai system 0-4

What system used for classification of CLL in Europe?

Binet systen (A,B,C)

-based on # of affected lymphoid tissues

-axillary, cervical, inguinal lymph nodes, spleen, liver

Cause of CLL

unknown but has genetic link

Uniqueness of CLL in peripheral blood smear

B lymphocytes mature when viewed in blood smear; other leukemias u cant differentiate between T and B lymphocytes

Clinical manifestations of CLL

-accumulation of lymphatic tissue (lymph nodes mostly)

-lymphadenopathy, splenomegaly, and or hepatomegaly

Other:

-night sweats

-fever

-unintentional weight lloss

-fatigue

-other clinical findings

CLL diagnosis

-Lymphocytosis - INC lymphocyte

-Bone marrow aspirate --> ID the type of leukemia (B in this case)

-Blood chemistry --> if B then there may be more antibodies

-Leukocytosis

Does multiple myeloma have a poor or good prognosis

poor

What is Multiple Myeloma

-INC # of malignant plasma cells

-occurs primarily in ppl over 60yrs old

-2x more common in blacks vs whites

Risk factors: toxins + hazardous chemical exposure, obesity,genetics

Clinical manifestations of multiple myeloma

Anemia, pain, pathologic fractures ( Ca2+ accumulation=weak bone) + hypercalcemia, renal insufficiency or failure

Treatment of multiple myeloma

Radiation + Chemotherapy

Stem cell transplantation

Treatments for anemia

(often times, by the time u ID MM it is too late and it prob alr metastasized a lot alr)

Classifications of lymphomas

Hodgkins (good prognosis)

Non-hodgkins

leukocytosis

too many WBCs

What is Non-Hodgkins lymphoma

-heterogenous group of malignancies

- swelling in different areas in Lymph nodes and diaphragm

-originates in the lymphatic susten

-common in the US

- 6th most common cancer in males

-5th most common in females

NHL cause and risk factors

Causes: unknown/idiopathic

RF: weakened immune system (can be HIV), Viral infections, Helicobacter pylori, common stomach infection, environmental factors like pollution

Pathogenesis of NHL

-genetic mutations

-solid tumors + localized, it is malignant however, it can be stuck in the lymph node but not always so can still spread to other parts

clinical manifestations of NHL

-lymphadenopathy

-extranodal disease

- gi tract, skin, liver, breast, bone, respiratory system, oral cavity ----> this is advanced lymphoma because it has metastasized

Hodgkin lymphoma is easier to treat ( + high cure rate)because

of the splitting of lymphatic system, its organized enough to be able to predict where the next swelling lymph node is

What is the classification system used for Hodgkin Lymphoma

Cotswolds modification of Ann Arbor Staging System, which is based on location of the tumor

HL has different subtypes that are differentiated by morphology, phenotypic analysis of Hodkin Reed-Sternberg HRS cells

HL causes and riskfactors

-unknown/idiopathic

-RF: familial factors, Viral exposures, immune suppression for both HL and NHL

-Pathogenesis: neoplastic process associated most commonly with B lymphocutes

- specific cell is Reed-Sternberg cell ( enlarged cells)

Clinical manifestations of HL

-enlarged lymph nodes; usually in neck

-splenomegaly

-hepatomegaly

Other symptoms:

-fevers,night sweats, fatigue, weight loss, alcohol induced pain, pruritus (scratching)

Anemia definition

reduction in the number of RBCs + decline in ability of RBCs to carry O2

Nutritional deficits of Anemia

Iron: it forms complexes (hemoglobin) and myoglobin ((rare because iron is fortified in lots of our foods))

Concepts related to pathophys of RBCS

-hypoxia

-loss of mature RBCs

-Genetic variation: prevents formation of mature RBCs or hemoglobin, Misshapen RBCs cause cells to clump together--> ischemia/hypoxia

-excessive RBC can cause blood to thicken

Classification of Anemia

-decreased prod. of RBCs

-Reduced survival time of RBCs

-Loss of RBCs (acute or chronic)

-Functional changes in the structure of RBC (sickle cell)

Lab tests: used to classify anemia or identify cause or risk for anemia

Morphology classification of anemia : Mean Corpuscular Volume (MCV)

-reflects avg. erythrocyte size/area that RBCs occupy

-Femtoliters (fL)

-Hematocrit (HCT)--RBC count

Microcytic vs. mactocytic anemia

Inc or Dec size of RBC

Mean Corpuscular hemoglobin (MCH)

-Hypochromic--> something makes hemoglobin not functional or enough/cell pale

-Normochromic --> normal color

Hematocrit def. and values

Proportion of RBCs to total blood volume

36-52%