Patho SU Final

Leukopenia

low WBC -below 5,000 -risk of infection

Stimuli for increasing erythropoiesis

low levels of O2 (hypoxemia) high altitude, increased exercise, loss of lung tissue in emphysema

metabolic acidosis (normal anion gap)

What fluid imbalance will result from cholera?

d-dimer which means there was a clot

What is a good test for DIC, PE, MI, CVA, DVT?

leukemia

cancer of hemopoietic tissue usually producing a very high number of circulating leukocytes

iron def anemia= low iron, high TIBC, low ferritin chronic disease=low iron, low TIBC, high ferritin

how can iron deficiency and anemia of chronic disease be differentiated?

respiratory, fecal-oral, or sexual routes

Most pathogens are transmitted from person to person by...

pathogenic, non-commensal organisms, which exhibit a wide range of virulence

Most infectious diseases are caused by...

3-5 days

RBC development takes how many days?

mononucleosis

S/s? -fever -sore throat -generalized lymphadenopathy -splenomegaly -*atypical activated T cells targeting B cells*

- petechiae - epistaxis - intracranial bleed treated with transfusion of platelets

What are complications of thrombocytopenia?

-lung disease -high altitude -cyanotic heart disease

What are some examples of secondary polycythemia?

both have high HCT look at EPO if low EPO = primary if high EPO = secondary

how can you tell the difference between primary and secondary polycythemia

HUS/TTP would have normal ptt/pt and no d-dimer

how could to you tell the difference between HUS/TTP and DIC?

-how much Hgb -saturation of Hgb

What determines the O2 on Hgb?

CD4, gp120

What does HIV bind to?

they might be anemic, so divide pt HCT by normal HCT

What does a corrected retic take into account?

blocks iron release from ferritin

What does hepcidin do?

TPA

What drug activates plasminogen to plasmin?

elevated in B12 deficiency -De-myelination in spinal columns -loss of proprioception and vibratory sensation

What effect does methylmalonic acid have on the body?

fresh frozen plasma due to clotting factors

how could you correct the effects of warfarin within 24 hours?

take out spleen

how could you fix spherocytosis (hemolytic anemia)?

plasma

What part of blood? -remainder of volume -47-63% -complex mixture of water, proteins, nutrients, electrolytes, hormones, nitrogenous waste, gases

WBC and platelets

What part of blood? 1% total volume, buffy coat

Erythrocytes (Hematocrit)

What part of blood? heaviest and settle first (37 to 52% of total volume)

factor 12

Which factor is associated with no bleeding disorder?

extravascular hemolysis

Which hemolysis uses C3b and IgG?

extravascular hemolysis

Which hemolysis? -jaundice due to too much bilirubin -kernicterus -normal haptoglobin levels -no hemoglobinuria

-leiomyoma = benign -leimyosarcoma = malignant

Which is malignant and which is benign? -leiomyoma -leimyosarcoma

sepsis

________ can lead to significant coagulation through direct action on factor 12 and endothelial activation

primary, secondary

_________ tuberculosis occurs in the nonimmune host and __________ tuberculosis occurs in the host who is immune to M. tuberculosis.

heparin

activate antithrombin III

What is methemoglobin?

an oxidized form of hemoglobin (Fe2+ --> Fe3+) that does NOT bind O2 as readily

120 days

average lifespan of RBC

direct coombs

does a patient have IgG antibody or c3b coating their RBC in their body

indirect coombs

does a patient have antibody floating in their plasma against foreign antigen

Spirochetes

double-membrane) bacteria, most of which have long, helically coiled (corkscrew-shaped or spiraled, hence the name) cells

significantly increase it.. therefor the heart has to generate higher pressure in order to produce same Cardiac Output

higher than normal HCT does what to blood viscosity?

vitamin K

how are effects of warfarin corrected after 24 hours?

latency

is defined as the persistence of viral genomes in cells that do not produce infectious virus

transferrin

main role of what? deliver iron from absorption centers in the duodenum and WBC macrophages to all tissues

macrocytic hyperchromic anemia

often stem from abnormalities that impair the maturation of erythroid precursors in the bone marrow -MCV >100 -cant divide

Clostridium botulinum

the cause of botulism, grows in inadequately cooked foods and releases a potent neurotoxin that *blocks synaptic release of acetylcholine and causes flaccid paralysis* of respiratory and skeletal muscles.

sickle cell trait

sickling in hypoxia (altitude, exertion, renal medulla)

microcytic anemia; normal ferritin; normal TIBC

thalassemias

MCV

the average volume of red cell expressed in femotilters

Transmission during birth.

this mode of transmission is caused by contact with infectious agents during passage through the birth canal (ex: HIV, chlamydia, gonorrhea)

leukemias

those arising from *blood-forming cells (WBCs)* are designated or Lymphomas (tumors of lymphocytes or their precursors)

anemia

too few RBCs

anemia

too few red blood cells

Polycythemia

too many RBCs

Polycythemia

too many red blood cells

daltons law of partial pressures

total pressure exerted by mixture of gases = sum of pressure exerted by each gas

Pleomorphism

variation in size and shape

-methylene blue (primary emergency treatment) -vitamin C (antioxidant)

what is the treatment for methemoglobinemia?

phlebotomy to drain of some blood and more importantly decrease iron levels

what is the treatment of iron overload

Stasis, endothelial injury and hypercoagulability

what is virchows triad

deficiency in b12

what leads to buildup in methylmalonic acid that is toxic to neuron>> eventually irreversible neurologic damage

direct coombs test looking for antibodies sitting on red blood cells.

what test would you do for autoimmune hemolytic anemia?

indirect coombs test looking for antibodies in blood

what test would you do to check moms Rh?

microcytic anemia

what type of anemia is due to a problem making hemoglobin?

Establishing latency

what type of immune invasion? during which viruses survive in a silent state in infected cells.

Suppressing the host adaptive immune response

what type of immune invasion? e.g. by interfering with cytokines or inhibiting MHC expression and antigen presentation. (especially MHC1 in all cells)

Resisting phagocytosis

what type of immune invasion? e.g. by producing a capsule •resistance to intracellular killing in phagocytes, including mycobacteria Tuberculosis

Inflammatory Responses to Infection

while generally beneficial, the host immune response to microbes can sometimes be the major cause of tissue injury in what?

kidneys

what is EPO controlled by?

Sarcomas

(cancers of mesenchymal tissue)

Secondary hemostasis

-coagulation with fibrin

bacterial overgrowth

Schilling test: give radioactive B12 + antibiotics and see it in urine?

-folic acid -amino acids -iron

What nutrients are necessary for making Hgb?

liver

Where are procoagulants made?

Dysplasia

disordered growth

folate deficiency

macrocytic anemia normal neuro exam and methymalonic acid levels

Epstein-Barr virus

•causes infectious mononucleosis, a benign, self-limited lymphoproliferative disorder, and is associated with the pathogenesis of several human tumors, most commonly certain lymphomas and nasopharyngeal carcinoma •transmitted by close human contact, frequently through the saliva during kissing • people with X-linked agammaglobulinemia (lack of B cells), who lack B cells, do not become latently infected with it or shed virus •*lymph nodes are typically discrete and enlarged* throughout the body •The *spleen is enlarged in most cases and at high risk of rupture*!!

Mumps

•is an acute systemic viral infection usually associated with *pain and swelling of the salivary glands* • viruses enter the upper respiratory tract through inhalation of respiratory droplets, spread to draining lymph nodes where they replicate in lymphocytes (preferentially in activated T cells), and then spread through the blood to the salivary and other glands -can cause *orchitis*

Giardiasis

•one of the most common causes of *waterborne* disease in the United States>>violent diarrhea, excess gas, stomach or abdominal cramps, upset stomach, and nausea •found in backcountry streams and lakes but also in municipal water supplies, swimming pools, whirlpool spas and wells •Boiling suspect water for one minute is the surest method to make water safe to drink •Chemical disinfectants or filters may be used

anaplasia

"to form backward," reversal of differentiation to a more primitive level

Heinz bodies

(in the corner)

prions

*misfolded proteins* • Unlike all other pathogens, they contain *no nucleic acids* • if this enters a healthy organism, it induces existing, properly folded proteins to convert into the disease-associated, prion form - *one misfolded protein can cause other misfolded proteins* • can be transmitted to humans by eating food contaminated with them • iatrogenic transmission, notably by corneal transplantation, deep implantation of electrodes in the brain, and administration of contaminated preparations of naturally derived human growth hormone Ex. *"mad cow" disease/Bovine spongiform encephalopathy (BSE) or when it has been transmitted to humans, variant Creutzfeldt-Jakob disease*

poliovirus

- causes an acute systemic viral infection, leading to a wide range of manifestations, from mild, self-limited infections to *paralysis of limb muscles and respiratory muscles* •most infections are asymptomatic, in about 1 of 100 infected persons poliovirus *invades the CNS and replicates in motor neurons of the spinal cord* •vaccines have nearly eradicated this, because it infects only humans, shows limited genetic variation, and is effectively neutralized by antibodies generated by immunization. Nevertheless, this scourge persists in parts of the developing world

Batson venous plexus

-*a route for metastasis to the spine* •a network of valveless veins in the human body that connect the deep pelvic veins and thoracic veins (draining the inferior end of the urinary bladder, breast and prostate) to the internal vertebral venous plexuses -*the reason why breast and prostate cancer spreads to the spine* •Because of their location and lack of valves, they are believed to provide a route for the spread of cancer metastases • Sluggish flow • Reflux due to lack of valves

TP53: Guardian of the Genome

-*controls DNA repair* a tumor suppressor gene that regulates cell cycle progression, DNA repair, cellular senescence, and apoptosis, is the *most frequently mutated gene in human cancers*.

Paraneoplastic Syndromes

-*make hormones* Some cancer-bearing individuals develop signs and symptoms that cannot readily be explained by the anatomic distribution of the tumor or by the elaboration of hormones indigenous to the tissue from which the tumor arose; these are known as ____________ • They may be the earliest manifestation of an occult neoplasm. • In affected patients they can cause significant clinical problems and may even be lethal. • They may mimic metastatic disease and therefore confound treatment. • *Hypercalcemia is probably the most common*

teratoma

-*mixed tumor* which contains recognizable mature or immature cells or tissues belonging to more than one germ cell layer (and sometimes all three); originates from totipotential germ cells that are normally present in the *ovary and testis*

febrile non-hemolytic reaction

-MC -fever and chills, and sometimes mild dyspnea within 6 hours of a transfusion of red cells or platelets -caused by inflammatory mediators derived from *donor leukocytes*

negative feedback of EPO

-drop in RBC count causes hypoxemia detected by kidney --> kidney production of erythropoietin --> RBC count increases in 3-4 days --> stop making EPO

Haemochromatosis

-high iron -low TIBC -high transferrin saturation -high ferritin

Iron poisoning

-high iron -normal TIBC -high transferrin saturation -normal ferritin

hemolytic anemia

-high iron -normal/low TIBC -high transferrin saturation -high ferritin

Haemochromatosis

-iron overload -accumulation of iron in the body from any cause

iron deficiency

-low iron -high TIBC -low transferrin saturation -low ferritin

Anemia of chronic disease

-low iron -low TIBC -low transferrin -high ferritin

chronic illness

-low iron -low TIBC -low transferrin saturation -normal/high ferritin

Zygomycosis (Mucormycosis)

-mold •an opportunistic infection caused by bread mold fungi, which belong to the family Mucormycetes. •characterized by hyphae growing in and around blood vessels and can be potentially life-threatening in diabetic or severely immunocompromised individuals •fungal invasion into the blood vessels which results in the formation of blood clots and surrounding tissue death • Major predisposing factors are: • neutropenia • corticosteroid use • diabetes mellitus • iron overload • breakdown of the cutaneous barrier (e.g., as a result of burns, surgical wounds, or trauma)

pregancy

-normal iron -high TIBC -low transferrin saturation

Sideroblastic anemia

-normal/high iron -normal/low TIBC -high transferrin saturation -high ferritin

primary hemostasis

-platelets form plug

candidiasis/Thrush

-yeast • Residing normally in the skin, mouth, gastrointestinal tract, and vagina, Candida species usually live as benign commensals and seldom produce disease in healthy people • Most commonly takes the form of a superficial infection on mucosal surfaces of the oral cavity (thrush) • Especially in newborns, debilitated people, children receiving oral steroids for asthma, and *following a course of broad-spectrum antibiotics that destroy competing normal bacterial flora*

What is the globin make-up of adult hemoglobin?

2 alphas, 2 betas

What is the globin make-up of fetal hemoglobin?

2 alphas, 2 gammas

3 mechanisms by which infectious agents establish infection and damage tissue

3 mechanisms by what? 1.They can contact or enter host cells and cause cell death *directly*, or cause changes in cellular metabolism and proliferation that can eventually lead to transformation. 2.They may *release toxins* that kill cells at a distance, release enzymes that degrade tissue components, or damage blood vessels and cause ischemic necrosis. 3.They can *induce host immune responses* that, though directed against the invader, cause additional tissue damage.

Metastasis

3 primary routes of? •(1) *direct* seeding of body cavities or surfaces •(2) *lymphatic* spread •The pattern of lymph node involvement follows the natural routes of lymphatic drainage •In breast cancer, determining the involvement of axillary lymph nodes is important for assessing the future course of the disease and for selecting suitable therapeutic strategies •A sentinel lymph node is defined as "the first node in a regional lymphatic basin that receives lymph flow from the primary tumor." Sentinel node mapping can be done by injection of radiolabeled tracers or colored dyes •(3) hematogenous spread via *blood* •Arteries, with their thicker walls, are less readily penetrated than are veins •With venous invasion, the bloodborne cells follow the venous flow draining the site of the neoplasm, and the tumor cells often come to rest in the first capillary bed they encounter •Understandably the liver and the lungs are most frequently involved in such hematogenous dissemination, because all portal area drainage flows to the liver and all caval blood flows to the lungs

macrocytic anemia causes

megaloblastic anemia b12 or folate deficiency

What does the indirect coombs test for?

Ab (Test for maternal blood)

anaerobic bacteria

Abscesses, Clostridial Infections

-antigenic variation -inactivating antibodies or complement -resisting phagocytosis -suppressing the host adaptive immune response -establishing latency

After bypassing host tissue barriers, infectious microorganisms must also evade host innate and adaptive immunity to successfully proliferate and be transmitted to the next host. Strategies include:

What does the direct coombs test for?

Ag-Ab complex (Test for Ab bound Rh+ fetal blood in an Rh- mother)

-lymphocytes -monocytes

Agranulocytes

left shift

Alkalosis or CO2 position would do what to the curve?

25% to 2 %!!

Anti-Retroviral therapy reduces Vertical Transmission rates from

How do you differentiate between folate and b12?

B12 deficiency is gonna lead to a buildup in methylmalonic acid --> neurotoxic

Cystadenoma

Benign epithelial neoplasms producing large cystic masses(ex. in the ovary)

Papillomas

Benign epithelial neoplasms producing microscopically or macroscopically visible fingerlike or warty projections from epithelial surfaces

melanoma

Cancer of melanocytes • *Most dangerous* • *Highly metastatic and resistant to chemotherapy* • Treated by wide surgical excision accompanied by immunotherapy

obligate intracellular bacteria

Chlamydial Infections, Rickettsial Infections

Leukemia

Damage to the bone marrow, by way of displacing the normal bone marrow cells with higher numbers of immature white blood cells, results in thrombocytopenia and anemia in addition to a reduction in the number of functional leukocytes even in the presence of leukocytosis

gram negative bacteria

E coli, Neisserial, Pertussis, Helicobacter pylori, Vibrio cholera

Oncogenes

Ex of what? Point mutations of *RAS* family genes constitute the most common type of abnormality in human tumors

transforming infections

Example of what type of infection? Epstein-Barr virus & Human Papilloma Virus.

chronic latent infections

Example of what type of infection? Herpes infections

1.the growth-promoting *proto-oncogenes* •The cell growth "*gas pedal*" that gets stuck on •Only one allele of a gene needs to be mutated 2.the growth-inhibiting *tumor suppressor genes* •The cell growth "brakes" that fail •Both alleles must be mutated (brakes and emergency brake) to fail 3.genes involved in *DNA repair* •The DNA repair mechanic 4.genes that regulate programmed cell death (*apoptosis*)

Four classes of normal regulatory genes are the principal targets of cancer-causing mutations?

urine, feces, bleeding (Men: 0.9mg/day & Women: 1.7 mg/day)

How is iron normally lost daily?

-Basophils -Eosinophils -Neutrophils (MC)

Granulocytes

Human Papilloma Virus

High-risk _______ are by far the most important factor in the development of *cervical cancer*!! Worldwide, cervical carcinoma is the third most common cancer in women, with an estimated 530,000 new cases in 2008, of which more than half are fatal

kill infected cell, not virus

How do you kill virus?

PTT

How do you monitor heparin (intrinsic pathway)?

PT

How do you monitor warfarin (extrinsic pathway)?

since it is water insoluble it must be bound to protein

How does bilirubin travel in blood?

Both alleles must be mutated (brakes and emergency brake) to fail

How many genes must fail for the growth-inhibiting *tumor suppressor genes* •The cell growth "brakes" that fail to be affected?

Only one allele of a gene needs to be mutated

How many genes must fail for the growth-promoting *proto-oncogenes* •The cell growth "*gas pedal*" that gets stuck on to be affected?

1.5 % in plasma -plasma goes out to cells 98.5% on HGB -storage

How much O2 is carried in the plasma and on Hgb?

spleen: recycles iron bleeding: loses iron

If RBCs are broken down in spleen what happens to iron vs if RBCs are lost in bleeding?

low grade

If you *can determine what tissue* the cancer originated from upon microscopic examination the tumor is well differentiated and it is

No -T helper cells produce IFN gamma that enables macrophages to contain TB infection

In TB test will someone who is HIV positive have a rxn to TB antigen?

caseous necrosis

In addition to stimulating macrophages to kill mycobacteria, the TH1 response orchestrates the formation of granulomas and

Na follows Cl and H20 through CFTR channel causing dehydration

In cholera what happens?

ohm's law of pathogenesis

Infectivity = Virulence/Resistance

tumor suppressor genes

Insensitivity to growth-inhibitory signals. Tumors may not respond to molecules that inhibit the proliferation of normal cells, usually because of inactivation of tumor suppressor genes that encode components of these growth inhibitory pathways. *The brakes have failed*

other morphologic changes

Lack of differentiation, or anaplasia, in malignant tumors is often associated with

#1 prostate #2 lung #3 colon

MC cancers in men?

#1 breast #2 lung #3 colon

MC cancers in women?

iron deficiency anemia

MC nutritional disorder in the world and results in clinical signs and sx that are mostly related to inadequate hgb synthesis

Sarcomas

Malignant tumors arising in solid *mesenchymal (connective) tissues* Greek sar = fleshy

nearly all penicillin and cephalosporin antibiotics

Methicillin-resistant S. aureus (MRSA) are resistant to what abx?

Men: 4.7-6.1 million Women: 4.2-5.4 million

Normal RBC lab values

4,500-10,000

Normal WBC lab values

Chlamydia and rickettsiae

Obligate intracellular bacteria -proliferate only within host cells, although some may survive outside of cells

Syphilis

Proliferative endarteritis *affecting small vessels* with a surrounding plasma cell-rich infiltrate is characteristic of all stages. Much of the pathology of this can be ascribed to the *ischemia produced by the vascular lesions*

sx of anemia

S/s for? pale, *fatigue*, weakness, malaise, increased CO; fatty change in the liver, myocardium, and kidney; HA, dimness in vision and faintness

hemolytic disease of the newborn

Rh antibodies attack fetal blood causing severe anemia and toxic brain syndrome

lung cancer

Risk factors for what? •smoke. Smoking cigarettes. • breathe tobacco smoke. • are exposed to radon gas. • are exposed to asbestos. • are exposed to other cancer-causing agents at work. These include uranium, arsenic, vinyl chloride, nickel chromates, coal products, mustard gas, chloromethyl ethers, gasoline, and diesel exhaust.

intestinal problem

Schilling Test: give radioactive B12 + enzymes + intrinsic factor + antibiotics and don't see it in urine?

then pernicious anemia (No intrinsic Factor)

Schilling test: -give radioactive B12 + intrinsic factor and see it in urine?

Don't have enzyme to work = pancreatic enzyme deficiency

Schilling test: -give radioactive B12 + pancreatic enzymes and see it in urine?

if you see radioactive B12 in urine: Dont have a problem with absorbing B12 if you dont see radioactive B12 in urine: cant absorb B12

Schilling test: -give radioactive B12 and see it in urine?

Oncogenes

Self-sufficiency in growth signals. Tumors have the capacity to proliferate without external stimuli, usually as a consequence of oncogene activation. *The gas pedal is stuck on*

gram positive bacteria

Staphylococcal, Streptococcal, and Enterococcal

spirochetes

Syphilis, Lyme Disease

secondary pulmonary tuberculosis

Tb that occurs in apex of upper lobes bc that is where the most O2 is? -ventilation and perfusion is low in the top of the lung but ventilation is greater than perfusion = lots of O2

Primary pulmonary tuberculosis

Tb that occurs in lower part of the upper lobe or the upper part of the lower lobe

cancer in developed vs non developed countries

There is remarkable geographic variation in the incidence of specific cancers that is believed to stem mainly from differences in exposure to environmental carcinogens (discussed later), suggesting that many (and perhaps even most) cancers are preventable. (ex. Kaposi Sarcoma has highest incidence among cancers in sub-saharan Africa due to AIDS) -*The incidence of breast cancer is much higher in the "developed" world*

lead to cancer

Transforming Viral Infections lead to what?

mycobacteria

Tuberculosis, Mycobacterium avium Complex Leprosy

Measles (Rubeola)

Two or three days after the start of symptoms, small white spots may form inside the mouth, known as *Koplik's spots*

-A = A antigen -B = B antigen -AB = A and B antigen -O = NO antigen

What antigens are present on? -A -B -AB -O

1. chronic microbial infections -ex: osteomyelitis, endocarditis 2. chronic immune disorders -ex: Rheumatoid arthritis 3. neoplasms -ex: lung/breast carcinoma, Hodgkin's lymphoma

What 3 groups can anemia of chronic disease be grouped into?

- blood vessels - platelets - coagulation

What 3 things usually cause hemorrhagic disorders?

abnormal bleeding time (but not a decrease in platelets) prolonged PTT (factor 8)

What abnormal blood tests will be seen in Von Willebrand disease?

cushings

What may small cell carcinoma secreting ACTH cause?

-A = B antibody -B = A antibody -AB = NO antibody -O = A and B antibody

What are the antibodies present for? -A -B -AB -O

decrease platelet aggregation and increase vasodilation

What are the effects of prostacyclin?

increase platelet aggregation and vasoconstriction

What are the effects of thromboxane A2?

1) culture (grow it out) 2)biochemical or serologic identification •Ex. the presence of antibodies •The use of specific stains and microscopy 3)molecular diagnosis PCR, POLYMERASE CHAIN REACTION, e.g., viral "LOAD" amazingly specific and sensitive (*take primers and look for DNA/RNA*)

What are the gold standards for diagnosis of infections?

causes of mechanical damage to RBCs -form schistocytes from smashing RBCs -DIC -Running: smash cells in feet -Valve disease: smash cells against valve

What are these causes for? -DIC -Running -Valve disease

DIC

What are these causes for? -septicemia, rattlesnake bite, incompatible blood transfusion

ways inflammatory response can be bad for the body

What are these examples of? •The *granulomatous inflammatory reaction to M. tuberculosis* sequesters the bacilli and prevents their spread, but it also can produce tissue damage and fibrosis •damage to hepatocytes following *hepatitis B virus and hepatitis C* virus infection is mainly due to the effects of the immune response on infected liver cells •Following infection with *S. pyogenes*, antibodies produced against the streptococcal M protein can cross-react with cardiac proteins and damage the heart, leading to *rheumatic heart disease* •*poststreptococcal glomerulonephritis* is caused by immune complexes formed between antistreptococcal antibodies and circulating streptococcal antigens

factor 12

What can be the link btw infection and coagulation (DIC)?

DNA mutations

What causes cancer?

No ATP, so Na/K ATPase pump doesnt work -sodium builds up in cell

What causes cell swelling in hypoxia?

killed by NK cells

What happens if a cell stops expressing MHC 1?

if you make a bunch of hepicidin you wont absorb iron and you block release iron from ferritin... leads to iron deficency (AKA anemia of chronic disease)

What happens if you make too much hepcidin?

excessive activation of platelets -platelet plugs for all over

What happens in HUS/TTP?

decreased blood O2 content triggers secretion of EPO

What happens in acute blood loss when pt given fluids?

-bleeding = high retic -prob making blood = low retic

What happens to a retic count if bleeding vs problem making blood?

gamma falls and beta rises

What happens to the gamma and beta chains on Hgb after birth?

as temp rises, solubility decreases (ex: cold soda hold carbonation better)

What happens to the solubility of a gas in water as the temp increases?

no brakes = cancer

What happens when a virus (ex HPV) wipes out RB (brakes)?

NSAIDs

What inhibits Cox?

Gluccocorticoids

What inhibits Phospholipase A2?

Aspirin

What inhibits thromboxane A2?

HgbA1 with glucose

What is Hgb A1C?

Rh antibodies

What is Rhogam?

types of WBCs

What is a differential WBC count show?

Measles (Rubeola)

What is a leading cause of vaccine-preventable death and illness worldwide

-expressed as % of RBCs -1-3% = normal

What is a reticulocyte count?

increased RBC mass

What is absolute increased HCT?

cancer

What is neutropenia common in?

decreased plasma volume

What is relative increased HCT?

Haemochromatosis

What is seen in a Prussian blue stain?

#1 is a priming event that leads to increased sequestration and sensitization of neutrophils in the microvasculature of the lung #2 primed neutrophils are then activated by a factor present in the transfused blood product (probably antibodies in the transfused blood product that recognize MHC antigens expressed on recipient neutrophils)

What is the 2 hit hypothesis in TRALI?

SIADH

What may small cell carcinoma secreting ADH cause?

-infants = E. Coli or GBS -young adults = N. meningitidis -older adults = S. pneumoniae or Listeria -chronic meningitis = TB

What is the MC cause of meningitis in -infants? -young adults? -older adults? -chronic meningitis?

Von Willebrand disease

What is the MC inherited bleeding disorder of humans?

RBC x 3 = Hgb Hgb x3 = HCT

What is the Multiples of three rule?

desmopressin or estrogen (OCP)

What is the Tx for Von Willebrand disease?

O2 delivered = Blood flow x O2 content of blood

What is the formula for oxygen delivered to the tissue?

MC: O LC: AB

What is the most common and least common blood types?

serum ferritin

What is the most specific lab test for iron deficiency anemia?

Hgb A1 -2 alpha and 2 beta chains

What is the normal adult Hgb?

inversely related as viscosity increases, flow decrease

What is the relationship btw flow and viscosity?

100% hyperbaric chamber -CO replaces O2 on Hgb, and only have little O2 in plasma -100% O2 replaces O2 that would have been on Hgb

What is the treatment for CO poisoning and why?

recipient = AB donor = O

What is the universal recipient and the universal donor?

Hypercalcemia

What may breast or renal carcinoma that secrete parathyroid hormone related protein cause?

Aspirin

What may cause this? prolonged bleeding time with normal platelets and normal PT/PTT?

polycythemia

What may renal carcinoma or hepatocellular carcinoma that secrete EPO cause?

bleeding time

What test checks platelets?

Pap test

What test helps dx and prevent cervical cancer?

indirect coombs

What test will test for anti Rh antibodies in preg women's plasma?

direct coombs

What test will test for autoimmune hemolytic anemia?

PT/PTT

What tests check coagulation?

hemolytic, intravascular anemia

What type of anemia is Paroxysmal nocturnal hemoglobinuria?

Packed RBCs

What type of blood products will raise HCT?

acute infections

What type of infections? Measles, Mumps, Poliovirus, West Nile Virus, Viral Hemorrhagic fevers.

acute

What type of leukemia sees blasts?

Herpes Simplex Virus-1

What virus? Fever blisters/ cold sores

Epstein-Barr virus

What virus? causes mono and leads to Burkett's lymphoma by increasing the rate of B-Cell proliferation and activation

• Varicella-Zoster Virus (VZV) (AKA herpes zoster)

What virus? chickenpox then latent in neurons>>shingles

Epstein-Barr virus

What virus? mature B cells are infected

Herpes Simplex Virus-2 (Genital herpes)

What virus? vesicles on the genital mucous membranes as well as on the external genitalia

cause HCT to increase

What will dehydration/decreased plasma do to HCT?

increase drastically

What will happen to serum ferritin if pt has infection or cancer?

Polyp

When a neoplasm—benign or malignant—produces a macroscopically visible projection above a mucosal surface and projects, for example, into the gastric or colonic lumen

meat = more Fe2+ greens = more Fe3+

When eating meats or leafy greens which has more Fe2+ and Fe3+?

-comes from liver to inhibit iron absorption when iron levels are full -produced when sick/have infection so bacteria cannot feed on iron(may cause anemia)

When is hepcidin produced?

-small amount in the plasma -large amount stuck to hemoglobin (hemoglobin replenishes plasma when it is used up in tissues)

Where is oxygen in the blood?

adult hgb

Which Hgb? two alpha and two beta chains

fetal hgb

Which Hgb? two alpha chains and two gamma chains

IgA deficiency -triggered by IgG Antibodies that recognize IgA

Which antibody deficiency is most likely to cause an allergic rxn to blood?

Acute leukemia

Which leukemia is derived from stems cells; primarily affects children?

intravascular hemolysis

Which type of hemolysis? -hemoglobinuria -decrease in haptoglobin levels

because abx don't work

Why are many vaccines targeted toward viruses?

it generates free radicals from ROS via Fenton reaction

Why is free iron toxic?

high

Will homocysteine be high or low in B12/folate deficiency?

left

Will stomach carcinoma spread to right or left supra clavicular node?

hypoxemia

a decrease in PaO2 dissolved in plasma

RB: Governor of Proliferation

a key *negative regulator* of the G1/S cell cycle transition, is directly or indirectly inactivated in most human cancers The transforming proteins of several oncogenic animal and human DNA viruses also act, in part, by neutralizing the growth-inhibitory activities of RB (ex. HPV!!)

increased

a left shit in curve= what in terms of affinity for O2?

parasites

a non-mutual symbiotic relationship between species, where one species, the parasite, benefits at the expense of the other, the host

virulence

a pathogen's ability to infect a resistant host

decreased

a right shit in curve= what in terms of affinity for O2?

coagulation

a series of enzymatic reaction in blood plasma that converts a soluble plasma protein (fibrinogen) into an insoluble fibrous protein (fibrin) essentially turning blood plasma into gel

transfusion-related acute lung injury

a severe, frequently fatal complication in which factors in a transfused blood product trigger the activation of neutrophils in the lungs microvascular

Virus

a small infectious agent that replicates only inside the living cells of other organisms!!

Aspergillosis

a ubiquitous mold that *causes allergies* (allergic bronchopulmonary aspergillosis) in otherwise healthy people and serious *sinusitis, pneumonia, and invasive disease in immunocompromised* individuals

thrombosis

abnormal clotting in an unbroken vessel?

Homocysteine

accepts methyl group and causes *endothelial damage and thrombosis*

-a shortened red cell life span below the normal 120 days -elevated EPO levels and compensatory increase in erythropoiesis -accumulation of hgb degradation products that are created as a part of the process of red cell hemolysis

all hemolytic anemia share what feature:

polarity

apical surface (upper) basal surface (lower)

acute leukemia

appears suddenly, progresses rapidly, death within months

CD8+ T-Cells

are the key providers of cancer immunity by checking MHC-1 for abnormal proteins and inducing apoptosis in cells presenting abnormal proteins in MHC-1.

platelet clots treated with antiplatelets (NSAIDs) - pale clots-not hemoglobin - triggered by rupture of atherosclerotic plaque - caused by turbulence (narrow vessel)

arterial clots are what kind of clots?

increase

as O2 binds hgb affinity for O2 does what? Ex: in lungs

decreases

as O2 is released. hgb affinity for O2 does what? Ex: in tissues

scurvy, ehler-danlos, &cushings

associated with microvascular bleeding that results collagen defects that weaken vessel walls

grading

based on degree of differentiation of the tumor cells

adenoma

benign epithelial neoplasm that arises from renal tubular cells growing in the form of numerous tightly clustered small glands

thrombotic disorders

blood clots form within intact blood vessel or within the chambers: -*Clot form when they shouldn't*

no, Fe has to be in the 2+ form (Hgb) to bind O2

can oxidized hgb (methemoglobin) with Fe3 bind O2?

yes, platelets do express A, B, O antigens and there is some loss in imcomplatible transfusion

can plasma cause an issue in transfusion?

Clostridium perfringens, Clostridium septicum

cause cellulitis and myonecrosis of traumatic and surgical wounds (gas gangrene), uterine myonecrosis often associated with illegal abortions, mild food poisoning, and infection of the small bowel associated with ischemia or neutropenia that often leads to severe sepsis.

delayed hemolytic reaction

caused by antibodies that recognize red cell antigens that the recipient was sensitized to previously, for example through a prior blood transfusion -usually *IgG*

microcytic hypochromic anemia

caused by disorders of hgb synthesis (MC iron deficiency) -MCV <80 -cant make Hgb

acute hemolytic reactions

caused by preformed *IgM* antibodies against donor RBCs that activate complement -MC caused by incompatible blood transfusion

malaria

caused by the intracellular parasite Plasmodium that *infects red blood cells* •90% of deaths from this occur in sub-Saharan Africa •transmitted by female Anopheles mosquitoes, which are widely distributed throughout Africa, Asia, and Latin America •Nearly all of the approximately 1500 new cases of malaria each year in the United States occur in travelers or immigrants •P. falciparum infection is associated with high levels of parasitemia, that may lead to severe *anemia (hemolytic)*, cerebral symptoms, renal failure, pulmonary edema, and death, depending on the susceptibility of the host •Several types of mutations affecting red cells (*sickle cell, thalassemia, G6pD deficiency*) are highly prevalent in parts of the world where malaria is endemic and are absent in other parts of the world>> heterozygotes have decreased infectivity to malaria probably due in part to reduced RBC life span

Methemoglobin (Fe3+)

causes a *leftward shift* of the oxygen-hgb dissociation curve, resulting in *decreased release of oxygen to the tissues*

S.aureus

causes a myriad of skin lesions (boils, carbuncles, impetigo, and scalded-skin syndrome) as well as abscesses, sepsis, osteomyelitis, pneumonia, endocarditis, food poisoning, and toxic shock syndrome

hereditary hemorrhagic telangiectasia

characterized by dilated, tortuous blood vessel (telangiectasia) within walls that bleed rapidly

Loss of polarity

cells grow in an anarchic, disorganized fashion. Especially evident in epithelial tumors or carcinomas

hematocrit

centrifuge blood to separate components

microcytic anemia; high ferritin; low TIBC

chronic disease

Secondary pulmonary tuberculosis

classically involves the apex of the upper lobes of one or both lungs.

thrombus

clot formed in an unbroken vessel?

breaks down collagen in basement membrane by tumor

collagenase

Colon>> liver then lung

common metastases: Colon to?

Breast>> lung & bone (*breaks down bone*)

common metastases: breast to?

•Lung>> brain • Actually the most common brain tumor

common metastases: lung to?

•Prostate>>bone (*builds bone*)

common metastases: prostate to?

decreased platelet production

conditions that depress marrow output marrow generally (such as aplastic anemia and leukemia) or affect megakaryocytes somewhat selectively (alcohol, HIV)

splenomegaly; autoinfarction -sickle cell

continual excessive removal of defective RBC by the spleen leads initially to ____ and then to _______ eventually resulting in large non-functional spleen

von Willebrand factor

critical for platelet adhesion in primary hemostasis (platelet plug formation)

hypoxia

decrease in PaO2 dissolved in the interstitial fluid

ischemia

decrease in arterial blood flow to a tissue

anemia

defined as a reduction of the total circulating red cell mass below normal limits

anemia

defined as a reduction of the total circulation RBC

carcinoma

demonstrates anaplasia and lack of polarity

henrys law

each gas dissolves in proportion to its partial pressure

normocytic anemia with low retic count

early chronic disease, early iron deficiency aplastic or leukemia

acute blood loss

effects are mainly due to the loss of intravascular volume, which if massive can lead to cardiovascular collapse, shock, and death

megaloblastic anemia -folic acid deficiency -B12 deficiency

elevated RDW can help diagnose what?

yeast

grow as a single cell.

cancer risk

environmental factors affecting? •*Smoking*, particularly of cigarettes, has been implicated in cancer of the mouth, pharynx, larynx, esophagus, pancreas, bladder, and most significantly, about 90% of lung cancer deaths •*Infectious agents*. About 15% of all cancers worldwide are believed to be caused directly or indirectly by infectious agents •*Alcohol* consumption (abuse) increases the risk of carcinomas of the oropharynx (excluding lip), larynx, and esophagus and, by the development of alcoholic cirrhosis, hepatocellular carcinoma •*Diet*. geographic variation in the incidences of stomach cancer, colorectal carcinoma, prostate carcinoma, and breast carcinoma has been ascribed to differences in diet. •*Obesity*. the most overweight individuals in the U.S. population have 52% (men) to 62% (women) higher death rates from cancer than do their slimmer counterparts •*Reproductive history*. lifelong cumulative exposure to estrogen stimulation, particularly if unopposed by progesterone, increases the risk of cancers of the breast and endometrium, tissues that are responsive to these hormones •A 1996 analysis of epidemiologic data from more than 50 studies worldwide by the Collaborative Group on Hormonal Factors in Breast Cancer found that women who were current or recent users of birth control pills had a slightly higher risk of developing breast cancer than women who had never used the pill •Not having children or having children later in life is a risk factor as well •*Environmental carcinogens*. Individuals may be exposed to carcinogenic factors when they go outside (e.g., ultraviolet [UV] rays, smog), drink well water (e.g., arsenic, particularly in Bangladesh), take certain medications (e.g., methotrexate), go to work (e.g., asbestos), or even while lounging at home (e.g., grilled meat, high-fat diet, alcohol).

mold

grown in multi-cellular filaments or hyphae

1: dietary lack 2; impaired absorbtion (ex:PPIs) 3 increase requirement (ex:preg) 4 chronic blood loss

etiologies of iron deficiency anemia

hemorrhagic disorders

excessive bleeding -*clots dont form when they should*

Mechanical damage Autoimmune Disease/infection

extrinsic RBC defects caused by

hemophilia B

factor 9 deficiency?

Von Willebrand Disease is associated with what coagulation factor deficiency?

factor VIII

Hemophilia A is . . .

factor VIII deficiency

apoferritin

ferritin that is not combined with iron is called what?

chords of billroth

found in red pulp of sinusoids of spleen and contain half of the human body monocytes

embolus

free floating clot?

Upper lip and above = basal cell Lower lip and below = squamous cell

general rule for squamous vs basal cell carcinoma: Upper lip and above? Lower lip and below?

bind free Hgb

haptoglobin

normochromic normocytic anemia

have diverse etiology but often include problems in bone marrow production or premature loss of erythrocytes -MCV 80-100

% RBCs

hematocrit

premature destruction of RBCs

hemolysis

production of new RBCs from bone marrow fails to compensate for loss of RBCs

hemolytic anemia

leukocytosis

high WBC -above 10,000 -caused by infection, allergy, cancer

through G6PD

how does methemoglobin get reduced back to hgb in order to bind O2?

placental-fetal tranmission

how is HIV transmitted in fetus?

bound to transferrin

how is iron transferred in the blood?

4

how many genes code for alpha

4

how many heme groups (iron) per Hgb?

4

how many protein chains (globins) in each Hgb?

ristocetin aggulatunation test

how to test for functional von willebrand factor

transferrin saturation % is the initial test of choice

how would you dx someone with iron overload?

iron deficiency anemia

hypochromic

shift to the left which would decrease O2 delivery to tissues It affects delivery bc it wont let go of O2 in tissues it is corrected because the fetus has a higher hct (polycythemia --> makes more Hgb)

if the affinity of fetal hgb is increased what direction would the shift of hgb affinity/dissociation curve? how would this affect delivery of O2 to tissues? how is the corrected in a fetus?

iron overload due to -ETOH -malignancy -inflammation

if transferrin saturation <45% with elevated Serum Ferritin

iron overload ruled out

if transferrin saturation <45% with normal Serum Ferritin

iron overload due to -HFE genotype

if transferrin saturation >45% with elevated Serum Ferritin

d-dimer which means there was a clot

if you are breaking up fibrin what will you see?

A1

if you dont have beta globin what cant you make

blood vessel problem

if you have a patient with petechia and purpura but all test are normal what is the cause?

the spleen

if you have extravacular hemolysis what is the most common location?

decreased platelet survival -glucocorticoids or splenectomy for treatment

immune thrombocytopenia, destruction is caused by deposition and antibodies or immune completes on platelets and platelet removal by the spleen (lupus)

anemia of chronic disease

impaired RBC production associated with chronic disease that produce systemic inflammation is perhaps the most common cause of anemia among hospitalized patients in the US

pathogen

in the oldest and broadest sense is anything that can produce disease

mitoses

in undifferentiated tumors, many cells are in *mitosis/dividing*, reflecting the high proliferative activity of the parenchymal cells. • Note: cells in mitosis are often seen in normal tissues exhibiting rapid turnover, such as the epithelial lining of the gut • More important as a morphologic feature of malignancy are atypical, bizarre mitotic figures, sometimes with tripolar, quadripolar, or multipolar spindles!!

extravascular hemolysis

in which, intravascular or extravascular hemolysis would spherocytes be?

hyperplasia

increase in cell number

hypertrophy

increase in cell size

chronic blood loss

induces anemia only when the rate of loss exceeds the regenerative capacity of the marrow or when iron reserve are deplete and iron deficiency anemia appears

brith control

inhibits anithrombin III

warfarin

inhibits the vitamin-k dependent synthesis of biologically active forms of the calcium-dependent clotting *factor 2,7,9,10*

B12 deficiency

macrocytic anemia abnormal neuro exam and methymalonic acid levels

normocytic anemia with high retic count

intrinsic RBC defects - membrane defects (spherocytosis; paroxysmal nocturnal hemoglobinuria) - abnormal hemoglobin (sickle cell) - deficient enzymes (G6PD) extrinsic problems - mechanical damage - autoimmune -disease/infection

Membrane defects (spherocytosis, Paroxysmal Nocturnal Hemoglobinuria) Abnormal Hemoglobin (sickle cell) Deficient enzymes (G6PD)

intrinsic RBC defects caused by

hepicidin

iron absorption is regulated by _____, a small circulating peptide that is synthesized and released from the liver in response to increaes in intrahepatic iron levels

microcytic anemia; low ferritin; high TIBC

iron deficiency anemia (late) high RDW when early

small cell carcinoma

is *highly malignant* cancer that most commonly arises in the lung • cells in small-cell carcinomas are smaller than normal cells, and barely have room for any cytoplasm • often more rapidly and widely metastatic than non-small cell lung carcinoma • may lead to ectopic production of hormones like *ADH and ACTH*!!!

lyme disease

is a common *arthropod-borne* illness caused by the spirochete, *Borrelia burgdorferi*, which can be localized or disseminated with a tendency to cause persistent *chronic arthritis* •in endemic areas, B. burgdorferi infects up to 50% of *ticks*

location

is a critical determinant of the clinical effects of both benign and malignant tumors • Ex. A small (1 cm) pituitary adenoma, although benign and possibly nonfunctional, can compress and destroy the surrounding normal gland and thus lead to serious hypopituitarism

low grade squamous cell carcinoma

is a keratin pearl low or high grade?

N. meningitidis

is a significant cause of bacterial meningitis, particularly among adolescents and young adults

measles

is an acute viral infection that affects multiple organs and causes a wide range of disease, from mild, self-limited infections to severe systemic manifestations. •Because of poor nutrition and lack of access to medical care, children in developing countries are 10 to 1000 times more likely to die than are children in developed countries •The *blotchy, reddish brown rash* of virus infection on the face, trunk, and proximal extremities is produced by dilated skin vessels, edema, and a mononuclear perivascular infiltrate

N. gonorrhoeae

is an important cause of sexually transmitted disease (STD), with more than 300,000 cases reported each year in the United States. It is second only to C. trachomatis among bacterial STDs

carcinoma

is cancer of epithelial origin

Pertussis, or whooping cough

is caused by the gram-negative coccobacillus Bordetella pertussis

metaplasia

is defined as the replacement of one type of cell with another type •iis nearly always found in association with tissue damage, repair, and regeneration. Often the replacing cell type is better suited to some alteration in the local environment • Ex. gastroesophageal reflux damages the squamous epithelium of the esoph¬agus, leading to its replacement by glandular (gastric or intestinal) epithelium >> *Barrett Esophagus*

infectivity

is the ability of a pathogen to establish an infection

What is pernicious anemia?

lack of intrinsic factor that leads to b12 deficiency

What are the causes of decreased B12 absorption?

lack of intrinsic factor, pancreatic enzyme decrease, bacterial overgrowth, intestinal dysfunction, damage, removal

macrocytic anemia

larger red cell are always associated with insufficient number of cells and problems with DNA synthesis

increased WBCs

leukocytosis

low WBCs

leukopenia

embolism

lodging of an embolus causing a blockage?

Thrombocytopenia

low number of platelets?

myeloma

malignant tumor of bone marrow

neoplasm

means "new growth," and a new growth is called _________(Tumor now has a similar meaning); In the modern era, a _________ can be defined as "a disorder of cell growth that is triggered by a series of acquired mutations affecting a single cell and its clonal progeny"

sarcoma

metastasis? hematogenous spread

carcinoma

metastasis? lymphatic spread -(lymphatic spread will become hematogenous at some point)

methemoglobinemia

methemoglobin level >3% -cyanosis (unoxygenated blood bc stuck in Fe3+) -chocolate colored blood (very dark)

high in B12 deficiency low/normal in folate deficiency

methylmalonic acid level increase in which condition?

neurons

methymalonic acid is toxic to what?

A problem with making hemoglobin leads to?

microcytic anemia

Anemia of chronic disease

microcytic with -high ferritin -low TIBC

iron deficiency anemia

microcytic with -low ferritin -high TIBC

thalassemia

microcytic with normal ferritin and TIBC

intrinsic

most ______ RBC defects are *hereditary* (sickle cells, G6PD)

extrinsic

most ______ causes are *acquired* (antibody mediated-hemolysis and malaria)

hemophilia A

most common types of hemophilia, factor 8 deficiency -prolonged PTT, normal PT

polycythemia vera

mutations that lead to EPO independent growth of red cells progenitors

150,000-450,000

normal platelet values

blood loss < 1 week or Non hemolytic (RBC not destroyed)

normocytic anemia with corrected retic count <2%

blood loss > 1 week or Hemolytic (RBC destroyed)

normocytic anemia with corrected retic count >3%

Paroxysmal nocturnal hemoglobinuria

not able to break down complement proteins due to lack of K protein

Abnormal nuclear morphology

nuclei are disproportionately large for the cell, with a nuclear-to-cytoplasm ratio that may approach 1 : 1 instead of the normal 1 : 4 or 1 : 6. The nuclear shape is variable and often irregular, and the chromatin is often coarsely clumped and distributed along the nuclear membrane, or more darkly stained than normal (hyperchromatic)

C. difficile

overgrows other intestinal flora in antibiotic-treated people, releases toxins, and causes pseudomembranous colitis

What is the significance of heinz bodies?

oxidative damage to hemoglobin

all cells low

pancytopenia

less (CFTR channel blocked)

people with CF are more or less likely to die from dehydration due to cholera?

hemostasis

process by which blood clots form at sites of vascular injury

bacterial infections

prokaryotic Microorganisms that can be treated with antibiotics

Clostridium tetani

proliferates in puncture wounds and in the umbilical stump of newborn infants and releases a potent neurotoxin that causes increased muscle tone and generalized spasms of skeletal muscles (lockjaw) by *blocking the action of the inhibitory neurotransmitter glycine on skeletal muscle = contraction* (*glycine usually blocks contraction*) • Tetanus toxoid (formalin-fixed tetanus toxin) is part of the DPT (diphtheria, pertussis, and tetanus) immunization, and this has greatly decreased the incidence of tetanus worldwide.

thalassemia

reduced expression of one of the globin chains

aplastic anemia

refers to a syndrome of chronic primary hematopoietic failure and attendant pancytopenia -non hemolytic anemia

reticulocyte

released from a bone marrow into peripheral blood. remain detectable for 1-2 days before maturing. A good marker for the rate of erythropoiesis

Howell-Jolly bodies

remnants of nuclei that normally would be detected by splenic macrophages and removed -seen in sickle cell disease -means spleen isn't working

metaplasia

replacing one cell type with another better suited to the stress

anemia of chronic disease

results in increased interleukin 6 which stimulates an increase of hepatic production of hepcidin which inhibits ferroportin, hepcidin not only reduces iron uptake and suppress iron release from macrophages

liposarcoma

sarcoma of adipocyte?

rhabdomyosarcoma

sarcoma of muscle myoblasts?

Ewing's sarcoma

sarcoma of neuron?

synovial sarcoma

sarcoma of stromal cell?

"Two hit" hypothesis

since there are 2 alleles for each of the tumor suppressor genes, both need to fail to remove their normal growth inhibition

hemolytic

spherocytosis is what type of anemia

What is the significance of howell-jolly bodies?

splenic autoinfarction

sickel cell disease

spontaneous sickling -vaso-occulsion -hemolysis

Metastasis

spread of a tumor to sites that are physically discontinuous with the primary tumor, and unequivocally marks a tumor as malignant, as by definition benign neoplasms do not metastasize

promotion

steps in chemical carcinogenesis? can induce tumors to arise from initiated cell but they are non tumorigenic by themselves

initiation

steps in chemical carcinogenesis? cause permanent DNA damage -irreversible and has memory

RDW

the coefficient of variation of the red cell -how variable is the size of RBCs

1) lymphocytosis with the characteristic atypical lymphocytes (actually activated T-Cells responding to the EBV-infected B-Cells) in the peripheral blood, (2) a positive *heterophile (anti- sheep/horse RBC) antibody* reaction (Monospot test), (3) a rising titer of specific antibodies for EBV antigens (viral capsid antigens, early antigens, or Epstein-Barr nuclear antigen)

the diagnosis of mono depends on?

Resistance:

the host's ability to resist infection by a virulent organism

Primary pulmonary tuberculosis

the inhaled bacilli implant in the distal airspaces of the lower part of the upper lobe or the upper part of the lower lobe, usually close to the pleura. Lack of a rapid, previously sensitized immune response allows spread to the hilar lymph nodes -*ghon complex*

O2 saturation

the percentage of binding sites on hgb bound by O2

Extravascular hemolysis

the presence of c3b or IgG on the surface of rbc is also recognized by receptors on the surface of splenic macrophages--> phagoctosis which leads to what?

Postnatal transmission (Ex. cytomegalovirus (CMV), human immunodeficiency virus (HIV), and hepatitis B virus (HBV)

transmission in maternal milk

vertical transmission

transmission of infectious agents from *mother to fetus* or newborn child is a common mode of transmission of certain pathogens

Lymphatic filariasis

transmitted by mosquitoes and is caused primarily by the nematode *Wuchereria bancrofti* • *Non-pitting edema due to blockage of lymphatics* • In severe and long-lasting infections a chronically swollen leg may develop tough subcutaneous fibrosis and epithelial hyperkeratosis, termed *elephantiasis*

Rocky Mountain spotted fever (rickettsia rickettsia)

transmitted to humans by dog *ticks*. It is most common in the southeastern and south-central United States. It begins as a nonspecific severe illness with fever, myalgias, and gastrointestinal distress, and progresses to a widespread macular then petechial rash that can involve the palms and soles.

ferritin

what is the storage form of iron? -intracellular protein

lymphoma

tumors of lymphocytes

What is the purpose of G6PD?

turns methemoglobin back into hemoglobin

carcinoma

types of? • Squamous cell carcinoma denotes a cancer in which the tumor cells resemble stratified squamous epithelium • adenocarcinoma denotes a lesion in which the neoplastic epithelial cells grow in a glandular pattern

microcytic anemia

typically have to do with problems in hgb synthesis -iron deficiency -anemia of chronic disease -thalassemia

myeloid leukemia

uncontrolled granulocyte production

lymphoid leukemia

uncontrolled lymphocyte or monocyte production

chronic leukemia

undetected for months, survival time 3 years

Paroxysmal nocturnal hemoglobinuria

wake up in morning with hgb in urine due to spontaneous complement activation

-tissue factor activates factor 7 (extrinsic) -collagen activates factor 12 -both activate thrombin which converts fibrinogen to fibrin for clot -then factor 13 comes in and connect all the fibrin strands

what activates coagulation?

stabilzes its for coagulation -no VWF = no factor 8

what affect does von willebrand factor have on factor 8?

1.lack of intrinsic factor (pernicious anemia) 2.pancreatic enzyme decrease (used to remove R factor and attach intrinsic factor) 3. bacterial overgrowth (no intrinsic factor) 4. intestinal dysfunction/damage/removal (cant absorb intrinsic factor)

what are the causes of decreased b12 absorption?

-congenital defects in G6PD or methemoglobin reductase -oxidizing drugs (dapsone for leprosy)

what are the causes of methemoglobinemia?

normal cell percentage disrupted, impaired clotting; anemia, opportunistic infection. the rapidly dividing cancerous basically crowd out the space and resources for other "normal" cells

what are the effects of leukemia

1. 7 to 10% dissolved in plasma 2. 20% bound to globin of hemoglobin (carbaminohemoglobin) 2. 70% transported as HCO3 in plasma

what are the three forms CO2 is transported in the blood?

1) ph/CO2 2) temperature 3) 2,3-biphosphoglycerate (2,3 BPG)

what are the three important conditions that affect the oxygen-hgb dissociation curve

1. carry O2 from the lungs to cell tissues 2. pick up CO2 from tissues and bring to lungs (less important)

what are the two function of the RBC

• Viruses • Bacteria • Fungi • Parasites • Prions

what are the types of pathogens?

clots richer in fibrin and RBCs treated with anticoagulants -due to stasis (no vessel wall damage)

what are venous clots?

presence of *heterophiles antibodies* and atypical lymphocytes

what are you looking for on a mono spot test?

problems with 1.ventilation 2.perfusion 3.diffusion in lung

what can cause a decrease in partial pressure of O2 in the blood

carbonic anhydrase bc CO2 is not water soluble

what converts CO2 to HCO3 in the RBC so it can be transported in blood?

serum transferrin -high ferritin (iron) = low TIBC (transferrin)

what does TIBC measure?

platelet function

what does bleeding time measure?

the antigens present on donors RBCs

what does blood typing examine?

the compatibility of the *antigens on the donors* RBCS with the *antibodies present in the recipients* plasma

what does cross matching examine

the antibodies present in the patients/recipients plasma -aka antibody screen

what does the indirect coombs test/ indirect antiglobulin test test for?

Thromboxane A2 and ADP-brings in more platelets and causes vasoconstriction

what does von willebrand factors produce?

the enitre infected cells

what does your body kill if you have a viral infection?

-temporary damage (increased lactic acid, decreased ATP production=cell swelling-na/k atpase -permanent damage leading to coagulative necrosis (ca entry, mitochondria damage, membrane damage)

what happens during tissue/cell hypoxia?

respiratory alkalosis(breathe off more CO2)--> left shift--> increased PaO2 (daltons law)(though still lower than it would be at sea level) --> increased 2,3 BPG --> right shift (the net is right shift due ti 2,3 BPG)

what happens to curve at high altitudes?

the precent saturation of hgb

what is measured with a pulse oximeter

b12

what is required for odd chain fatty acid metabolism?

lung cancer

what is the MC cancer killer that is non sex specific?

converts fibrinogen to fibrin

what is the function of thrombin?

results in oxidative damage to hemoglobin and cell membrane of TBC

what is the issue with G6PD?

venous and arterial thrombosis

what is the issue with HIT?

-spontaneous complement activation

what is the issue with Paroxysmal nocturnal hemoglobinuria?

prevents absorption of iron leading to iron deficiency anemia -cant convert Fe3+ to Fe2+ (acid helps conversion)

what is the issue with taking PPIs?

it puts pts at risk for pneumococcus and h influenza septicemia -*infection is the principal cause of death* in pts who have sickle cell disease world wide( early diagnosis is vaccination is key)

what is the issue with the splenic dysfunction in sickle cell disease?

Eliminating endothelial integrity (causing endothelial damage)

what is the most important factor in virchows triad?

Antigenic variation

what type of immune invasion? •Influenza viruses have a complex RNA genome that allows for frequent recombination events, permitting antigenic "drift" and "shifts" •low fidelity of viral RNA polymerases of HIV and many respiratory viruses (including influenza virus)

Inactivating antibodies or complement

what type of immune invasion? •changes in net surface charge and membrane hydrophobicity that prevent antimicrobial peptide insertion and pore formation, secretion of proteins that inactivate or degrade the peptides, and pumps that export the peptides

respiratory and diarrheal infection

what types of infectious disease take the greatest toll and make infectious disease six of the ten leading causes of death in developing countries?

1. amount of O2 dissolved in plasma (PaO2 x Solubility) 2.% saturation of hgb with O2 3. hgb concentration level 4. blood flow to tissues or whole body (CO)

what variables affect the amount of oxygen delivered to tissues?

during mechanical rbc damage

when will you see schistocytes?

liver and mononuclear phagocytes

where are the major sites of iron storage?

in the brain to prevent bleeding

where is the most tissue factor located in the body?

Normocytic anemia

which anemia reflects an imbalance in normal RBC production vs destruction or loss

CO2 is 20x more soluble in water than O2. little N2 dissolves in water

which is more soluble in water O2 or CO2?

chronic leukemia

which leukemia is more prevalent in older people?

cellular metabolism -produce ATP

why do we need oxygen?

oxygen has very poor water solubility and the red blood cell is a large savings account for oxygen to make sure the plasma always has O2

why do we need red blood cells

the fetus must get its O2 from mom

why does fetal hgb have a higher affinity to O2 than adult hgb

anaerobic fermentation to produce ATP -so they dont use up O2

why does the RBC lack mitochondria?

no protein synthesis or mitosis -so they dont use up O2

why is there lack of nucleus and DNA in a RBC

gram positive bacteria

will retain the crystal violet dye in the peptidoglycan layer and are stained violet and while the gram negative bacteria do not and will stain pink

Two general processes are involved in cancer-associated hypercalcemia:

• (1) *osteolysis induced by cancer*, whether primary in bone, such as multiple myeloma, or metastatic to bone from any primary lesion, and •(2) the production of *parathyroid hormone-related protein (PTHRP)*, a molecule related to, but distinct from, parathyroid hormone (PTH) •In breast cancers, hypercalcemia due to PTHRP production is often exacerbated by osteolytic bone metastases. •Note; Only the second mechanism is considered to be paraneoplastic; hypercalcemia due to primary or secondary involvement of the skeleton by tumor is not a paraneoplastic syndrome

basal cell carcinoma

• *Least malignant; most common* • *Stratum basale* cells proliferate and slowly invade dermis and hypodermis • Cured by surgical excision in 99% of cases

squamous cell carcinoma

• *Second most common type of carcinoma* • Involves keratinocytes of *stratum spinosum* • Usually scaly reddened papule on scalp, ears, lower lip, and hands • Does metastasize • Good prognosis if treated by radiation therapy or removed surgically

Cryptococcosis

• *best known for causing a severe form of meningitis and meningo-encephalitis in people with HIV/AIDS* • found in the droppings of wild birds, often *pigeons*; when dust of the droppings is stirred up it can infect humans or pets that inhale the dust

ABCD rule for diagnosing melanomas

• A: asymmetry; the two sides of the pigmented area do not match • B: border irregularity; exhibits indentations • C: color; contains several (black, brown, tan, sometimes red or blue) • D: diameter; larger than 6 mm (size of pencil eraser)

renal carcinoma

• In adults, the most common type of kidney cancer is *renal cell carcinoma* • Young children are more likely to develop a kind of kidney cancer called *Wilms' tumor* • Renal cell carcinoma often invades the branches of the renal vein and then the renal vein itself, from where it may grow in a snakelike fashion up the inferior vena cava, sometimes reaching the right side of the heart • Often *produce EPO --> polycythemia and parathyroid hormone-related protein (PTHRP) --> hypercalcemia*

development of cancer

• Nonlethal genetic damage lies at the heart of carcinogenesis. • A tumor is formed by the clonal expansion of a single precursor cell that has incurred genetic damage (i.e., tumors are clonal). • Loss-of-function mutations in genes that maintain genomic integrity (ex. p53) appear to be a common early step on the road to malignancy, particularly in solid tumors. • Once established, tumors evolve genetically during their outgrowth and progression under the pressure of Darwinian selection (survival of the fittest)

Mycobacterium species

• The distinguishing characteristic of all ___________________is that the cell wall is thicker than in many other bacteria, being hydrophobic, waxy, and rich in mycolic acids/mycolates>>>which makes them *acid-fast*, meaning they will retain stains even on treatment with a mixture of acid and alcohol

local invasion

• The growth of cancers is accompanied by progressive infiltration, invasion, and destruction of the surrounding tissue, whereas nearly all benign tumors grow as cohesive expansile masses that remain localized to their site of origin and lack the capacity to infiltrate, invade, or metastasize to distant sites. • Because benign tumors grow and expand slowly, they usually develop a rim of compressed fibrous tissue called a capsule that separates them from the host tissue

i) genetic material made from either *DNA or RNA*, long molecules that carry genetic information ii) *protein coat* that protects these genes iii) sometimes, an *envelope of lipids* that surrounds the protein coat when they are outside a cell.

• Virus particles (known as virions) consist of what two or three parts:

E.coli

• a major facultative inhabitant of the *large intestine* •The *urinary tract* is the most common site of this infection, and more than 90% of all uncomplicated UTIs are caused by this nfection!!! •Shiga toxin-producing ______(STEC) is among the *most common causes of foodborne diseases*. This organism is responsible for several GI illnesses, including nonbloody and bloody diarrhea •An important cause of *meningitis in neonates*

Dysplasia

• encountered principally in epithelia • exhibit considerable pleomorphism and often contain large hyperchromatic nuclei with a high nuclear-to-cytoplasmic ratio. • The architecture of the tissue may be disorderly • *When these changes are marked and involve the full thickness of the epithelium, but the lesion does not penetrate the basement membrane, it is considered a preinvasive neoplasm and is referred to as carcinoma in situ (Fig. 7-10). Once the tumor cells breach the basement membrane, the tumor is said to be invasive.*

Helicobacter pylori

• spiral-shaped or curved bacilli present in gastric biopsy specimens of almost all patients with duodenal ulcers as well as most individuals with *gastric ulcers or chronic gastritis* •*The most common cause of chronic gastritis* •Up to 85% of people infected with this never experience symptoms or complications

Stage: TNM (Tumor Nodes Metastases)

•Cancer stage refers to the size and/or extent (reach) of the original (primary) tumor and whether or not cancer cells have spread in the body (in order of prognostic significance T<N<M)

Chlamydia

•Genital infection is the *most common sexually transmitted bacterial disease in the world* •clinical features that are similar to those caused by N. gonorrhoeae. Patients may develop epididymitis, prostatitis, pelvic inflammatory disease, pharyngitis, conjunctivitis, perihepatic inflammation, and proctitis

Abscesses

•Many anaerobic bacteria are normal flora in sites of the body that have low oxygen levels. •The anaerobic flora cause disease when they are introduced into normally sterile sites or when the balance of organisms is upset and pathogenic anaerobes overgrow (e.g., Clostridium difficile colitis with antibiotic treatment) •Commensal bacteria from adjacent sites (oropharynx, intestine, and female genital tract) are the usual cause of this, so the species found in an abscess often reflect the normal flora in that site. -prevents spread of infection to other parts of body

Host defenses against infection

•Skin: tough keratinized barrier, low pH, fatty acids •Respiratory system: alveolar macrophages, mucociliary clearance by bronchial epithelium, IgA •GI system: acidic gastric pH, viscous mucus, pancreatic enzymes and bile, defensins, IgA, and normal flora •Urogenital tract: repeated flushing and acidic environment created by commensal flora

high grade

•These tumors tend to grow and spread less aggressively and at a slower rate •If you *can't determine what tissue* the cancer originated from upon microscopic examination due to a lack of differentiation (termed Anaplasia) it is

Pertussis, or whooping cough

•an acute, *highly communicable* illness characterized by parox¬ysms of violent coughing followed by a loud inspiratory "*whoop*." •In the United States, the incidence of pertussis has risen dramatically, with large epidemics occurring in 2005, 2010, and 2012 (linked to decreased vaccination) •B. pertussis colonizes the brush border of the bronchial epithelium and also invades macrophages •pertussis toxin subunits impair host defenses by inhibiting neutrophils and macrophages and *paralyzing cilia*, among other effects. •In areas of the developing world where vaccination is not widely practiced, pertussis kills hundreds of thousands of children each year!!!!