Pathoma CBSE

Hypoxia; Hypoxemia

________ is when there is low O2 delivery to tissues in general, while __________ is specifically when the cause of low O2 delivery to tissues is low O2 saturation in the BLOOD.

hemoglobin

Carbon monoxide poisoning results in “cherry-red” skin because CO binds to ____________ more avidly than O2.

Methemoglobinemia

_________________ is when oxidative stress (from sulfa or nitrate drugs) cause the iron in heme to be oxidized from the Fe2+ form to the Fe3+ form. This means it can no longer bind O2, and the oxidized iron in the blood turns it into “chocolate-colored blood.”

Liquefactive; Microglia; Coagulative

Ischemic infarction in the brain (i.e. stroke) leads to ___________ necrosis because the brain is the only tissue that contains ____________ cells (they release hydrolytic enzymes that lyse the necrotic brain tissue). This is opposed to how ischemic infarction in ANY other organ leads to _____________ necrosis.

Calcium

Fat necrosis usually presents with a “chalky-white” appearance because dead fat can undergo saponification, in which __________ deposits in the tissue.

c-Myc

Bcl2 is an anti-apoptotic protein that works by trapping _______ in the mitochondria. If it is released from the mitochondria, then it stimulates caspases and subsequent apoptosis.

CD95; target

FAS ligand can bind to FAS death receptor (________) on the __________ cell.

Perforin; Granzymes

CD8+ T-cells mediate apoptosis by secreting _________ to create pores in the membrane of the target cell. Then they secrete ___________ to enter the cell and activate caspases.

NADPH Oxidase; Chronic Granulomatous Disease (CGD)

___________________ is the enzyme responsible for converting O2 into superoxide (O2-) during an oxidative burst killing. A defect in this enzyme results in ________________________, which renders patients particularly susceptible to infection with catalase-positive organisms.

Superoxide Dismutase

___________________ is the enzyme responsible for converting superoxide (O2-) into hydrogen peroxide (H2O2).

Myeloperoxidase; Candida

______________ is the enzyme responsible for converting hydrogen peroxide (H2O2) into bleach (HOCl). Deficiency in this enzyme (i.e. MPO Deficiency), results in increased risk of ____________ infections.

PGE2 and Bradykinin

What are the two mediators of PAIN?

Willebrand Factor and P-selectin

Weibel-Palade bodies are found in endothelial cells, and they contain what 2 important proteins?

CD18 Integrins

Leukocyte Adhesion Deficiency (LAD) is due to an autosomal recessive defect of ___________________. Without it, neutrophils have impaired adhesion to endothelial cells (resulting in delayed umbilical cord separation, increased circulating neutrophils, and recurrent bacterial infections WITHOUT pus formation).

Chediak-Higashi Syndrome

_______________________ is an autosomal recessive protein trafficking defect that results in impaired fusion of the phagolysosome. It also presents with albinism and peripheral neuropathy.

IL-8; IL-10 and TGF-Beta

Macrophages secrete _______ to recruit more neutrophils and prolong the inflammatory response, but they secrete _________ and _________ to initiate the healing response.

B7; CD28

The “second activation signal” for CD4+ Helper T-cells consists of ____ on the antigen presenting cell (APC) binding to _____ on the Helper T-cell.

CD40L; CD40

The “second activation signal” for B-cells consists of ____ on the Helper T-cell binding to the _________ on the B-cell.

Epithelioid histiocytes

__________________ are the defining cell type present within a granuloma.

22q11 microdeletion

DiGeorge Syndrome is due to a _______________ that results in failure of the 3rd and 4th pharyngeal pouches to form. So, they have T-cell deficiency because they have NO THYMUS.

Adenosine deaminase

SCID is when both B-cell and T-cell immunity is impaired, and one possible etiology is a deficiency in _________________, as adenosine buildup is toxic to lymphocytes.

BTK; 6 months

X-Linked Agammaglobulinemia is due to a mutation in _______, which means pre- and pro-B-cells can no longer mature. Thus, they will have a complete LACK OF ANTIBODIES, but will really only present after _________ of life (once maternal antibodies are gone).

IgA Deficiency; mucosal

____________ is the most common immunoglobulin deficiency, and patients are at an increased risk for __________ infections. It is common in patients with Celiac Disease.

CD40 or CD40L

Hyper IgM Syndrome is due to mutated __________________, and it means B-cells can no longer receive the second-signal to class switch their antibodies. So, they will have high IgM levels, but low levels of IgA, IgG, and IgE.

WASP; Thrombocytopenia, Eczema, and Recurrent Infections

Wiskott Aldrich Syndrome is due to mutations in the _______ gene, which is X-linked. The triad of symptoms include: ______________, _____________, and _______________.

Hereditary angioedema

C1 Inhibitor Deficiency results in ____________________ (especially periorbital) because the complement cascade is overactivated and leads to widespread edema.

AIRE; Hypoparathyroidism, Adrenal failure, Chronic candida infection

Autoimmune Polyendocrine Syndrome is due to mutations in the ________ gene. It is typically responsible for upregulating transcription of self-antigens for central tolerance, but without it, autoimmune cells get out into the periphery and target endocrine glands. The resulting symptoms include: ______________, _____________, __________________.

FoxP3; Immune Dysregulation, Polyendocrinopathy, and Enteropathy

IPEX Syndrome is due to _________ mutations. It results in impaired Treg function, and subsequent 1) _________________, 2) ___________________, 3) ________________, and it is X-linked.

Antibody-Antigen Complexes; anti-dsDNA and anti-Sm

Systemic Lupus Erythematosus is due to the formation of ___________________ (type 3 HSR) that deposit in tissues and cause damage. These complexes originated from UV damage and poorly-cleared apoptotic debris activating self-reactive cells. Specific antibodies include ___________ and ___________.

Sjogren’s Syndrome

_________________ is characterized by lymphocyte-mediated destruction (type IV HSR) of salivary and lacrimal glands.

Sjogren’s Syndrome

Neonatal lupus can develop when pregnant women with _________________ pass on the anti-SSA antibody.

Calcinosis, Raynaud Phenomenon, Esophageal Dysmotility, Sclerodactyly, Telangectasia’s

Systemic Sclerosis is characterized by CREST Syndrome. CREST stands for:

Fibroblasts (depositing type 3 collagen), Capillaries, and Myofibroblasts (to contract the wound)

Granulation tissue consists of what 3 elements?

3; 1; Zinc

Collagenase is the enzyme that replaces type ____ collagen in granulation tissue with type ____ collagen. It requires _______ as a cofactor.

>6:1

The normal kappa:lambda light chain ratio is 3:1, but in lymphoma, the ratio becomes _____________ because the cancer cells are MONOCLONAL.

Adenoma or Adenocarcinoma

Tumors of epithelium that produce GLANDS are called either _____________ or _______________.

Papilloma or Papillary carcinoma

Tumors of epithelium that produce PAPILLARY GROWTHS are called either _____________ or _______________.

Chondroma or Chondrosarcoma

Tumors of Cartilage Mesenchyme are called either ___________ or ________________.

Osteoma or Osteosarcoma

Tumors of Bone Mesenchyme are called either ___________ or ________________.

Lipoma or Liposarcoma

Tumors of Fat Mesenchyme are called either ___________ or ________________.

Angioma or Angiosarcoma

Tumors of Blood Vessel Mesenchyme are called either ___________ or ________________.

hepatocellular carcinoma

Aflatoxins generated by Aspergillus are known to cause what kind of cancer?

Leukemia/Lymphoma

Alkylating agents used in chemotherapy are known to cause what type of cancer?

Squamous cell carcinoma of the skin and lung cancer

Arsenic is known to cause what two types of cancer?

Stomach carcinoma (intestinal type)

Nitrosamines found in smoked foods are known to cause what type of cancer?

Angiosarcoma of the liver

Vinyl Chloride used in PVC pipe manufacturing is known to cause what type of cancer?

Nasopharyngeal carcinoma and Burkitt Lymphoma

EBV is known to cause what two types of cancer?

Kaposi Sarcoma

HHV-8 is known to cause what type of cancer?

Hepatocellular carcinoma

HBV and HCV are known to cause what type of cancer?

Adult T-cell leukemia/lymphoma

HTLV-1 is known to cause what type of cancer?

Squamous cell carcinoma of the vulva, vagina, anus, and cervix.

High-risk HPV subtypes (16, 18, 31, and 33) are known to cause what types of cancer?

RAS

______ is an oncogene that is active when bound to GTP, and when it gets mutated, it loses its intrinsic GTPase ability and is constitutively active → cancer.

BAX; Bcl2

Normally functioning p53 activates ______ when it detects DNA damage, which then leads to _______ degradation. Remember that “____” is what stabilizes the mitochondrial membrane and keeps c-Myc contained, so it’s degradation leads to c-Myc release and subsequent apoptosis of a damaged cell.

BAX; Bcl2

Mutated p53 can no longer activate ______, which means _______ is constitutively active and preventing apoptosis of cancer cells.

Li-Fraumeni Syndrome

____________________ is when someone inherits a germline mutation in p53, so they are prone to developing carcinomas and sarcomas because they only need one “hit” to lose their other working copy of p53.

E2F; CyclinD/CDK4 complex

Normally functioning Rb binds to ________ and inhibits it from stimulating the G1 → S transition of the cell cycle. If the cell wants to progress through the cell cycle, then the _________________ must phosphorylate Rb, causing it to release E2F.

PDGFB

__________ oncogene overexpression is associated with development of an astrocytoma.

RET

______ oncogene mutation is associated with development of MEN2A, MEN2B, and sporadic medullary carcinoma of the thyroid.

VWF; GP1b; GPIIb/GPIIIa; Fibrinogen

In primary hemostasis, _____ binds to exposed collagen, and then platelets bind to that VWF via _______. The platelets then upregulate surface expression of ____________, and then they aggregate using _________ as the linking molecule between GPIIb/GPIIIa.

Platelets; Skin and Mucosal

Disorders of PRIMARY hemostasis are usually due to defects in _____________, and they present clinically with excess _______ and _________ bleeding.

Immune Thrombocytopenic Purpura

______________________________ is due to autoimmune production of IgG antibodies against GPIIb or GPIIIa, leading to platelet destruction by splenic macrophages.

Thrombotic Thrombocytopenic Purpura

________________________________ is due to autoantibodies against ADAMTS13. ADAMTS13 usually cleaves VWF, so its destruction leads to excess VWF and excess platelet consumption (i.e. microthrombi formation).

Schistocytes

TTP/HUS are known to produce what type of RBC on peripheral smear?

Hemolytic Uremic Syndrome

_______________________ is due to E. coli O157:H7 production of verotoxin, which damages endothelial cells (particularly in the kidney) and results in the formation of platelet microthrombi.

Bernard-Soulier Syndrome

_____________________ is due to a genetic GP1B deficiency, so platelet adhesion to VWF is impaired. It presents with enlarged platelets on blood smear (mnemonic: “Big Suckers”)

Glanzmann Thrombasthenia

_______________________ is due to a genetic GPIIb/GPIIIa deficiency, so platelet aggregation to each other via fibrinogen is impaired.

COX; Thromboxane-A2

Aspirin impairs platelet aggregation by irreversibly inactivating ______, thus decreasing production of _______________.

Coagulation Cascade; deep tissue, joint, and postsurgical bleeding

Disorders of SECONDARY hemostasis are usually due to defects in the _____________, and they present clinically with __________________________________.

8; 9

Hemophilia A is due to a genetic factor ____ deficiency, while Hemophilia B is due to a genetic factor _____ deficiency.

Platelet adhesion; stabilization of factor 8

Von Willebrand disease is due to a genetic VWF deficiency. It affects both PRIMARY AND SECONDARY hemostasis because it is needed for 1) ________________, but also 2) _________________ in the coagulation cascade.

Increased; Increased; Normal

Von Willebrand Disease will present with (increased/decreased/normal) bleeding time, (increased/decreased/normal) PTT, and (increased/decreased/normal) PT.

2, 7, 9, 10, and Protein C and S

Vitamin K is required to activate factors:

PF4; Heparin-PF4

Heparin-Induced Thrombocytopenia occurs when heparin forms a complex with _______ on platelets, and then IgG antibodies can target that _____________ complex and lead to platelet degradation.

Disseminated Intravascular Coagulation

____________________________ would have the following laboratory findings:

1. Decreased platelet count

2. Increased PT/PTT

3. Decreased Fibrinogen

4. Increased D-Dimer

Decreased; Increased; Decreased; Increased

Disseminated Intravascular Coagulation will present with (increased/decreased/normal) platelet count, (increased/decreased/normal) PT and PTT, (increased/decreased/normal) fibrinogen, and (increased/decreased/normal) D-dimer.

Cross-linked fibrin

D-dimer is produced when _______________ is cleaved.

tPA; fibrin and fibrinogen

_______ converts plasminogen → plasmin. Then, plasmin cleaves _________ and ________ to remove thrombi.

a2-antiplasmin

____________ inactivates plasmin, so it prevents plasmin from cleaving fibrin and fibrinogen (thus prevents clot breakdown).

Protein C and S

Warfarin Skin necrosis may occur in the initial stage of warfarin therapy due to temporary deficiency of _________ and ____________ relative to Factors 2, 7, 9, and 10. Considering their job is to provide negative feedback to the coagulation cascade, their absence increases risk for thrombosis in the skin.

Factor V Leiden

___________________ is the most common inherited cause of a hypercoaguable state, and it is characterized by a mutated form of factor V that cannot be cleaved by either protein C or S.

TTP; HUS

Although they are both microangiopathic hemolytic anemias, _______ is more likely to cause CNS abnormalities, while _______ is more likely to cause renal insufficiency.

TTP

ITP and TTP differ in that _____ is the only one that will produce schistocytes due to the formation of platelet microthrombi.

ITP

Between ITP and TTP, ______ usually occurs in children a few weeks after a viral infection or immunization.

Thrombin; Fibrin

The end goal of the coagulation cascade is to produce ___________, which converts fibrinogen → __________.

Normal

DIC and disorders of fibrinolysis can present very similarly, but the fibrinolytic disorders will have a (increased/decreased/normal) platelet count.

DIC

One of the classic examples of a cause of ________ is venom from a rattlesnake bite.

Duodenum

Iron is absorbed primarily in the __________.

Ferroportin; Transferrin; Ferritin

Once absorbed by gut enterocytes, iron is transported into the bloodstream via ____________, at which point it binds to ____________. That then delivers the iron into liver and bone marrow macrophages for storage (where it is bound to ______________).

AL; AA

____ Amyloid comes from lambda (Ig) light chains, so they’re typically implicated in plasma cell dyscrasias. ____ Amyloid comes from Serum Amyloid-A protein, which is usually associated with chronic inflammation.

Beta2 Microglobulin

In dialysis-associated amyloidosis, _______________ likes to deposit in JOINTS.

Positive; Negative

Type 1 Error is a false ___________, while Type 2 Error is a false ____________.

1

The type ____ error rate is synonymous with the p-value. So, it is usually a 5% chance.

2

The type ____ error rate is equal to the power of the study subtracted from 100. So, 80% power would have a 20% error rate.

Creatinine; Inulin

_____________ is used to measure GFR as a rough estimate because it is freely filtered AND actively secreted. A better measure of GFR is __________ because it is freely filtered but NOT actively secreted or reabsorbed.

Acidic

Calcium Oxalate, Uric Acid, and Cystine crystals form in (acidic/basic) environments.

Phosphate; Secondary Hyperparathyroidism

Chronic Kidney Disease leads to a buildup of __________ in the blood, which then binds to free Ca2+ and decreases serum Ca2+ levels. This leads to __________________________. Damaged kidneys also lose the ability to activate Vitamin D, so we won’t even be able to absorb Ca2+ from the gut as well.

Ureteric bud; Metanephros

In renal embryology, the __________ forms a pouch off of the mesonephric duct, and that pouch growing into the _____________ is what results in the development of a kidney.

Common Iliac Artery

One of the most common locations for a kidney stone to get lodged is when the ureter crosses over the __________________ in the pelvic.

Minimal Change Disease; Focal Segmental Glomerulosclerosis

The two nephrotic syndromes that are due to effacement of podocyte foot processes are _________________ and ______________________.

Cytokines; Negative

Minimal change disease is due to ___________ damaging podocyte foot processes and effacing them. That said, the glomeruli will appear normal, and the immunofluorescence will be ____________.