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Pathology block 2

Terms in this set (682)

Mendelian disorders characteristics/examples of codominance

result from mutations in single genes with large effects

- dominant or recessive
- co-dominance: blood groups; both alleles contribute to phenotype

What are characteristics of autosomal dominance?

uta- manifested in heterozygous state

- defect in every generation

- delayed onset
- reduced penetrance and variable expressivity

What is mutated in autosomal dominant disorders?

regulatory proteins and structural proteins

Marfan Syndrome
- mutation
- inheritance pattern
- chromosome affected

CT disorder primarily in changes of skeleton, eye, and cardiovascular system

- defect in fibrillin (FBN1) major component of ECF
- chromosome 15q21

Skeletal abnormalities in patients with Marfan Syndrome

tall, thin habitus with long extremities

Dolichocephaly (head long and thin)
Arachnodactyly
Scoliosis, kyphosis

restrictive lung disease (chest wall/rib problems)

Ocular and Cardiovascular changes in patient with Marfan

ocular - lens is fine, retinal detachment

CV - mitral valve prolapse (CT weak, pushes valve into LA)

neurofibromatosis

What disease is associated with the following presentations?

Ehlers-Danlos syndrome
- defect
- presentation

heterogenous group of disorder that result from defect in collagen synthesis/structure

skin: hyper-extensible, fragile, easy bruising, very stretchy

joints: hypermobile
contortionists

Classic form (type I/II) Ehlers-Danlos Syndrome:
- mutation

mutation in the genes for Type V collagen (COL5A1 and COL5A2)

Kyphoscoliosis EDS (type VI)

- mutations
- presentation
- common inheritance

- mutation in the gene encoding lysyl hydroxylase

eyes: rupture of cornea and retinal detachment (like Marfan)

most common autosomal recessive form of EDS (exception)

body habitus more normal (unlike Marfan stature)

Neurofibromatosis define

neurofibromas; benign tumors
(-oma)

Type I Neurofibromatosis 3 major features:

1. multiple neural tumors (neurofibroma)

2. pigmented nodules of the iris (Lisch nodules)

3. cutaneous hyper-pigmented macules (cafe au lait spots)

Presentations and chromosome affected in Type I neurofibromatosis

NF1 tumor suppressor gene (17q11.2)

associated with skeletal lesions and other tumors such as malignant peripheral nerve sheath tumors, gliomas of the optic nerve, other glial hamaratomatous lesions, and pheochromocytoma

Type 2 Acoustic Neurofibromatosis
- presentation
- gene associated
- patient complaints
- aka

associated with bilateral acoustic schwannomas and multiple meningiomas

cranial nerve 8 (acoustic)

gene: NF2- tumor suppressor gene

disease of the two's (type 2, only 2/3 presentation, 2 sides affected, on chromosome 22)

presentation:
tinnitus bilateral / vertigo
cafe au lait present

von Hippel-Lindau disease
- associated diseases
- gene
- presentation

hemangioblastomas of CNS and cysts of pancreas, liver, kidney (most common in the cerebellum and retina)

VHL gene: tumor suppressor gene on chrom.3

renal cell carcinoma (multiple and bilateral)

cerebellar hemangioblastoma
- children

What is occurring?

retinal hemangioblastoma
- adults
- filled inside of blood vessels

What is pictured?

Hemangioblastomas in cerebellum associated with what presentations

common in children

child with issue balancing since compressing the cerebellum

ataxia (gait)

headaches, hydrocephalus

Hemagioblastoma of retina presentation:

common in adults
seen being filled with blood vessels

adults with visual problems; child has gait problems

Familial Hypercholesterolemia
- gene
- inheritance
- heterozygote presentation vs. homozygotes

LDL receptor gene
- defective LDL transport/ increased synthesis

one of the most frequent mendelian disorders

heterozygotes: 2-3x increase of plasma cholesterol; xanthomas; premature atherosclerosis

homozygotes: 5-6x increase of plasma cholesterol; MI before 20 y/o

Treatment for familial hypercholesterolemia
- MOA

statins to decrease cholesterol via suppressing intracellular cholesterol synthesis through inhibition of enzyme HMG CoA reductase = increase LDL receptors

Characteristics of autosomal dominant disorders

manifest in homozygous
25% chance sibling affected

uniform expression of defect

onset early in life

What are the likely mutations associated with autosomal dominant disorders?

loss of function of enzyme proteins

lysosomal storage diseases (location is key)

Tay Sachs
- mutation
- demographic
- accumulating substance
- timeframe

mutation in alpha--subunit --> hexosaminidase A deficiency

- Ashkenazi jews

- accumulation of GM2 into various tissues, including CNS

- early age onset ~ 6 months

Tay Sachs
-ballooning of neurons

Presentation of patients with Tay Sachs Disease:
- Sx and death time frame

ballooning of the neurons with whorled configuration of lysosomes (EM)

motor and mental deterioration (delayed milestones)

cherry red spot on macula

death by 2 to 3 y/o

Neimann-Pick disease type A
- deficiency
- accumulation
- death

deficiency: sphingomyelinase
most common
severe infantile form with extensive neuro involvement, marked visceral accumulation of sphingomyelin, progressive wasting

death within first 3 years

ft: hepatospenomegaly, generalized lymphadenopathy

Neimann-pick disease type B
- accumulation
- sites affected
- clinical features
- death

organomegaly but no CNS involvement

accumulation of sphingomyelin in RES, CNS, and eye

RES: lipid-laden foamy macrophages in liver, spleen, lymph nodes, bone marrow, etc.

CNS: vacuolation/ballooning of neurons

eye: retinal cherry-spot

death within first or second year

Gaucher
- deficiency
- accumulation
- demographic
- key to differentiate
- pathological change MOA

deficiency of glucocerebrosidase

- most common lysosomal storage disorder

- European Jews
- accumulation of glucocerebrosides in mononuclear phagocytes (of RES) called Gaucher cells (key)

pathological changes caused by accumulation and activation of macrophages and cytokine secretions (IL-1, IL-6, TNF)

Clinical features seen in an adult with Gaucher (commonly):

infant?

prognosis?

splenomegaly, pancytopenia/thrombocytopenia, pathological fractures (osteoporosis)

infant: neurological involvement

prognosis: progressive form is compatible with long life

PAS stain to light up glucocerebrosides in cytoplasm of macrophages

- Gaucher disease

wrinkled tissue paper in cytoplasm

Stain, features:

Mucopolysaccharidoses
- deficiency
- most associated features
- 2 subtypes

deficient in lysosomal enzymes involved in degradation of GAGs: dermatan sulfate, heparan sulfate, keratan sulfate, chondroitin sulfate

associated:
coarse facial features, clouding of the cornea. (worse prognosis)
joint stiffness, mental retardation

seen in mucopolysaccharidoses

- due to GAGs building up in different areas of the face
"gargoylism"
Graves, hypothyroidism seen too

What are the causes of coarse facial features>

Seen in hurler's --> so Hurler's has a worse prognosis than Hunter

Where is this seen?

Hurler Syndrome
- deficiency
- clinical presentation
- prognosis

(MPS I-H)

alpha-1-iduronidase deficiency

hepatospenomegaly by 6-24 months, growth retardation
death by 6-10 years

Hunter syndrome
- inheritance
- clinical features
- prognosis

X-linked recessive
no clouding of the cornea

milder clinical course

"Hunter is old school and uses a cross-bow"

Von Gierke's Disease

hepatic form
deficiency of glucose-6-phosphate

hepatomegaly and hypoglycemia (confused/disoriented)

myopathic form
deficiency of muscle phosphorylase

muscle weakness and cramps after exercise

deficiency of alpha-glucosidase (acid maltase)

cardiomegaly - glycogen builds up and causes restrictive cardiomyopathy -- unable to open well in diastole and fill --> biventricular heart failure

clear vacuoles represent glycogen inside myocardial fibers

- restrictive cardiomyopathy

What is pictured?

Characteristics of X-linked disorders
- inheritance
- carriers
- affected

usually recessive

no male to male transmission

carrier: all daughters of affected males
- female siblings of patient may have mild symptoms

sons of heterozygotes:
- 50% chance of receiving mutant

X-linked dominant --> vitamin-D resistant rickets (female)

If patient has vitamin-D resistant rickets, what occurs when they are treated with vitamin D infusions?

disorders with multifactorial inheritance:

combined action of environmental influences and 2+mutant genes

Ex: hair, eyes, skin, height, intelligence

likely of both identical twins being affected significantly <100%
(normally in twins, there is 100% concordance like in Lupus)

FISH (fluorescent in situ hybridization)

adjunct to karyotyping and cytogenic analysis

exact multiple of haploid number
ex: triploid = 69

chromosome is not an exact multiple of 23
- neoplasia importance - malignancy more aggressive

hyperploidy is better prognosis

one less chromosome via nondisjunction

- cri du chat (5p-)

one extra chromosome

most commonly associated with spontaneous abortion

Trisomy 21
- clinical features
- incidence related to:

most common chromosomal disorder/cause of mental retardation in U.S.

incidence related to maternal age (35 y/o increased chance)

extra chromosome is of maternla origiin

Clinical features:
- flat facial profile
- palpebral fissures
- epicanthic folds
- Simian creases (single palmar crease/ no opposition)
- severe mental retardation

Other diseases associated with Trisomy 21

congenital heart disease - ostium primum, atrial septal. defects (general pop. commonly ostium secondum)

Acute leukemia (ALL/AML)

Alzheimer disease

Hirschbrung disease (congenital megacolon)

Trisomy 18 (Edwards Syndrome)
- clinical features
- prognosis

micrognathia (small mandible)
prominent occiput
rocker bottom feet (also in Patau)
congenital heart defects (VSD)

death within 1 year
(child/adult has to be Down syndrome)

Trisomy 13 (Patau Syndrome)
- clinical features
- prognosis

microcephaly
micropthalmia
cleft lip and palate
rocker bottom feet
polydactyly

death within 6 months

What is the Lyon hypothesis?

One of females X chromosomes are inactivated by XIST

inactivated X chromosome seen in all cells derived from precursor cell and represented as Barr body
(#X chromosome - 1)

Klinefelter syndrome
-clinical features

male hypogonadism occurring when there are 2+ X chromosomes and one or more Y chromosomes

47,XXY (have barr body)

tall, thin eunuchoid body habitus (also in Marfan)

small atrophic testes (increased estradiol)

gynecomastia (breast development)

reduced intelligence

increased plasma FSH and estradiol levels

Barr body present

"big breasteses, small testeses"

Turner syndrome
- causes what?
- characteristic
- clinical features

complete/partial monosomy of X chromosome (no Barr)

hypogonadism in phenotypic females

most common sex chromosome abnormality in females

45, XO
short stature
webbing of neck
wide set nipples
streak ovaries
coarctation of aorta
normal mental status

True hermaphroditism

presence of testicular and ovarian tissue in same individual (extremely rare)

pseudo hermaphroditism

represents a disagreement between phenotypic and gonadal sex

Testicular feminization

male pseudo-hermaphoditism (most common form)

associated with androgen sensitivity in the male

Single-gene disorders with non-classical inheritance are classified into 4 categories:

triple repeat mutations (Fredrich Ataxia)
Mutations in mitochondrial genes
genomic imprinting
gonadal mosaicism

Fragile X Syndrome
- mutation
- distinctive feature / clinical presentation

mutation: long repeating sequence of 3 nucleotides on X chromosome mapped to FMR1 gene

2nd most common cause of mental retardation

distinctive: macro-orchidism (large testes)

other features: long face with large mandible, large everted ears

Prader-Willi Syndrome
- mutation
- presentation

micro-deletion on paternal chromosome 15

mental retardation, obesity, hypogonadism

Angelman (happy puppet) syndrome

UBE3A gene -- maternal chromosome

mental retardation, seizures, ataxia (gives appearance of puppet on string), inappropriate laughter

"all mothers are angels"

What is a hypersensitivity reaction?

- why does is it result?

excess/harmful reaction to antigen that the individual has been previously exposed to

- results from an imbalance between effector mechanisms of immune responses / control mechanisms to control responses

How is type I HSR response described?

immediate response

What is the defining characteristic of Type II HSR?

antibody mediated

Type III hypersensitivity reaction mediated by what?

immune complex mediated

Type IV is a ___ mediated reaction

Type I HSR:
- triggering event
- disorder/reaction that can occur

antigen binding to IgE antibody on surface of mast cells

systemic reaction or local reactino

What is the cause/result of a systemic reaction in a Type I HSR?

follows an injection of antigen into a sensitized individual (bee sting) or following ingestion (peanut)

What molecules can cause anaphylactic shock for the systemic vasodilation?

local reactions in HSR I presentations:

- what are the phases?

local cutaneous rash/blisters
allergic rhinitis/conjunctivitis

1. immediate phase
2. late phase

Immediate reaction in HSR I:
- physiological characteristics
- what mediates these reactions

vasodilation, vascular leakage, glandular secretions

- histamine release by mast cells

Late phase reaction in HSR I:
- physiological characteristics
- what is resulting damage
- what cells are recruited

infiltration of tissues with eosinophils, neutrophils, basophils, CD4 T cells

- leukocytes recruited
tissue damage in the form of mucosal epithelial cell damage

What are most immediate hypersensitivity disorders caused by:

excessive TH2 responses which produce IgE and promote inflammation

When does mast cell activation occur?

after IgE cross linking with antigen
-

Eosinophils liberate what substances?

proteolytic enzymes -- major basic protein and eosinophilic cationic protein
- damaging tissues

Primary mediator of HSR I reaction:

Secondary mediators of HSR I:

leukotrienes which are responsible for bronchospasms/bronchoconstriction associated with asthma (also by histamine)

Which HSR are represented in the picture?

immediate (erythema) and late phase (edema from vascular permeability)

When a HSR becomes systemic, what happens to the larynx?

- what do you need to do to the patient?

laryngeal edema -> patient needs to be intubated

systemic vasodilation leads to:
- Sx

shock
- skin warmth (A,S,N shock)

HSR II
- mediated by:
- Ab association
- classic cell

mediated by cytotoxic antibodies (IgG, IgM)

- antibody binding to antigens on cell surface

classic cell = RBC

Which reactions fall under HSR II?

1. transfusion reaction
2. drugs that bind to RBC (penicillin)

3. hemolytic anemia (SLE)

Steps of a type II HSR:

1. form cytotoxic antibodies
2. antibody binding to antigens on cell surface
3. complement dependent phagocytosis or lysis
4. complement independent (ADCC)

Erythroblastosis fetalis
- characteristics
- which HSR

type II HSR
- hemolytic disease of the newborn; lots of erythroblasts being produced by baby in liver and spleen

Autoimmune hemolytic disease
- HSR?
- characterisitics

HSR II
- certain drug reactions

Which HSR is Graves disease?
- what is affected

HSR II
TSH receptor antibody
- Graves is a result of up-regulation

Which HSR is Myasthenia Gravis?
- what is affected

HSR II
- Ach receptor antibody
- a result of decreased activity

How can you differentiate Myasthenia Gravis from Lambert Eaton?

MG: muscle weakness, worse through the day

LE: muscle weakness gets better
- Ab to Ca channels at pre-synaptic membrane

Which cancer is associated with Lambert Eaton?

small cell/oats carcinoma of the lung

How is Type III HSR mediated?
- Preferential sites and their associated diseases

immune complexes

glomerulonephritis (kidney), arthritis (joints), vasculitis (small vessels)

What is an example of a local Type III HSR reaction?

Arthrus
- booster shot associated; reaction to horse Ab

What type of necrosis is associated with Type III HSR?

Fibrinoid necrosis (from neutrophils releasing enzymes) --> thrombi

EX: SLE

In active SLE infection, where is complement taking place and what are the consequences in serum?

all complement occurring in wall of the blood vessels
- serum complement levels will be low

What is affected in vasculitis?
- predominant cell type?

The entire wall involved in necrosis
- dark cells would be neutrophils

What is an example of a local immune complex reaction?

arthrus reaction
- experimental vasculitis

Type IV HSR is __ mediated. and is considered a ___ type hypersensitivity.

cell mediated
- delayed type HSR (DTH)

Steps of a type IV HSR:
- example of type IV HSR

1. CD4 T cell recognition of antigen associated with MHC
2. Lymphokine production (IL-2, IFN-y)
3. recruit and activate macrophages
4. granuloma formation

Ex: TB

When would a reaction occur in a type IV HSR?
- what type of test is an example of this

occurs within 1-3 days (24-72 hours)

- Tb test pt comes back wihtin 48 hours

Target cells of cytotoxicity in Type IV HSR
- example of this reaction

virus-infected cells, tumor cells, transplanted cells

contact dermatitis with Poison Ivy (severe form in pic)

What will react against graft antigens that will destroy tissue grafts?

The major antigenic difference between a donor and recipient that results in a rejection of transplants are differences in:

Direct graft recognition:
- attacks
- cells involved

most attacks the graft parenchyma/tissue in general

- dendritic cell of graft to T cell of the host

Indirect graft rejection:
- attacks
- cells involved

APC of host present to T cell
- get more humoral immunity which attacks blood vessels --> vasculitis

- attack of blood vessels = different prognosis and therapy

2 mechanisms of graft rejection:

1. T cell mediated cytotoxicity (direct)
- destruction of graft interstitial cells

2. Antibody mediated reaction (indirect)
- destruction of graft vasculature

Hyperacute transplant rejection

- occurs within minutes to hours
- due to pre-formed antibodies to transplant

Ig and complement deposited in vessel wall --> endothelial injury/thrombi (normally type III)

kidney cortex undergoes necrosis

What are the typical serum levels/urine characteristics in a patient with kidney failures?

rise in creatinine and BUN
- oliguria (decreased output of urine)

What type of infarct occurs in Type IV associated kidney failure?
- MOA

Ab attack blood vessel --> damage endothelium --> thrombi --> white/pale infarct--> kidney will NOT survive

Acute transplant rejection (pathogenesis)

within days of transplantation/suddenly months or years later (after immunosuppression is tapered/terminated)

Clinical signs of acute transplant rejection:

sudden onset fever
graft tenderness
acute renal failure

Which immune mechanisms predominate in acute transplant rejection?

cellular or humoral

If there is a a graft infarct, which transplant rejections could be presenting, and what distinguishes between them?

acute or hyperacute

time frame distinguishes (hyper = min-hrs; acute = days/mo/yrs)

Cellular immune mechanism (transplant rejection)
- how can you test to see if this is the mechanism occurring?

extensive interstitial inflammation (lymphocytes)

- can give high dose immunosuppressive therapy and they respond

Humoral Immune mechanism (transplant rejection)
- how can you test for this?

associated with deposition of the complement breakdown product C4d (preceded during activation of ADCC)

- results in infarct -- will not respond to high dose immunosuppressive therapy

What is the histological presentation of acute cellular rejection?

a lot of lymphocytes
- attack the parenchyma (like tubule)

What will the outside of the kidney appear as if there is acute rejection?

dark areas that may be areas of hemorrhage

What are the defining characteristics of chronic transplant rejection? How would the patient present?

years later
- presents clinically with progressive renal failure manifested manifested by a rise in serum creatinine (over 4-6 months)

What is the morphology that occurs in chronic transplant rejection?

dominated by vascular changes
1. intimal thickening
2. glomerulopathy (duplication of BM)
3. peritubular capillaritis (mulitlayering of BM)

What is the histology presentation of a patient with chronic transplant rejection?
- MOA

cell mediated
- lymphocytes involve the blood vessel
- slow narrowing of the lumen --> ischemia --> atrophy

endothelial cell hyperplasia
- tubules below the blood vessels are atrophic

PIC:
dots are lymphocytes that release cytokines to stimulate cell proliferation (= multiple glomeruli)

What is the mechanism of cyclosporine?

blocks the activation of TF for cytokine genes (IL-2)

- block proliferation in BM; prevent host system from attacking the graft

Mechanism for Azthioprine as an immunosuppressive agent

inhibits leukocyte development from bone marrow precursors

mechanism for monoclonal anti-T cell Ab as immunosuppressive agent:

opsonize and eliminate T cells

Mechanism for mycophenolate mofetil as immunosuppressive agent

inhibits lymphocyte proliferation

Mechanism for Tacrolimus (FK506) as immunosuppressive agent

used a lot
- inhibits T cell function

Which opportunistic infection is a classic presentation in transplant patients on immunosuppressive therapy?

CMV is classic for transplants

What is the appearance of the kidney if a patient presents with chronic renal failure/ end-stage renal disease?

appear as if they have benign chronic HTN

atherosclerosis (AAA risk) seen in the aorta

Where is a transplanted kidney placed?

more anteriorly as a precaution, for better access

Graft vs. Host
- when it occurs
- classic patient
- classic transplant

when immunologically competent cells or their precursors are transplanted into immunologically crippled patients

- AID/SCID patients = classic

- site = hematopoietic stem cell transplantation

Injuries that occur in a graft vs. host rejection:

1. skin (rash) -- burn-like appearance

2. GI (diarrhea and abdominal pain)

3. liver (increased enzymes: ALT, AST) + jaundice

When will a bone marrow transplant rejection appear?

EX: tissue + mechanism of damage

very fast - within days

- begins to attack patient tissues -- liver biopsy = cholestasis = conjugated bilirubin building up from liver failure = jaundice

What is an example of a single organ disease?

What is an example of a multi-systemic disease?

Theories of autoimmunity

clonal anergy
clonal deletion

Theories of autoimmunity MOA and processes

- decreased suppressor T cell function
- increased helper T cell function
- release of sequestered antigen
polyclonal B cell activation
self-antigen modification by drugs/microorganisms
cross reaction (antigen with similar makeup to normal tissue)

Examples of autoimmune release of sequestered antigen:

lens crystallin
sperm

What is the genetic factor HLA-DR3 associated with?

Type I DM
SLE, Sjorgen syndrome, graves, MG

What is the genetic factor HLA-DR4 associated with?

Type 1 DM, Rheumatoid arthritis

What is the genetic factor HLA-B27 associated with?

ankylosing spondylitis
- bony fusion of the spine (young males); extraintestinal manifestation of IBD

Homogenous (diffuse) nuclear pattern
- MOA

in certain disease, Ab against a portion of the nucleus so immunofluorescence shows which is involved to help diagnose

Rim (peripheral) pattern ANA
- disease association

sometimes in ds DNA

seen in homogenous; common for person with autoimmune disease to get another one

Speckled nuclear pattern

speckling of RNA and DNA

Nucleolar pattern on immunoflouresence

Antibodies to RNA

ANA- anti-nuclear antibody; sensitive but not specific so cannot be used to make a diagnosis

systemic lupus erythematosus (SLE)
- demographic commonly affected
- timeframe presentation

chronic; remitting and relapsing illness characterized by injury to skin, joints, kidneys, and serosal membrane

- common and severe in African American women
~20-30s

What is the etiology of SLE?

failure of regulatory mechanisms that sustain self-tolerance

- ANA sensitive but nonspecific for SLE

- Abs to dsDNA and Smith antigen = virtually diagnostic for SLE

- anti-phospholipid Abs
- Abs against RBC, WBC, platelets

What is the mechanism of anti-phospholipid antibodies?

bind to cardiolipin causing biological false positive test for syphillus (VDRL)

May alter in vitro clotting test of PTT (Lupus anti-coagulant)

Pathogenesis of SLE
- genetic
- environment
- immunological factors

1. Genetic factors:
- increase risk in family members

2. environmental: certain drugs, sex hormones, UV light

3. immunological factors: helper T cell-dependent B-cell response, Type III HSR (fibrinoid necrosis)

What is the effect of SLE on the skin?

erythema of facial (butterfly) area exacerbated by sun -- aka maculopapular rash, facial, malar

liquefaction of epidermal basal layer with vasculitis

deposit of Ig and complement at derm-epidermal junction on IF

What will you see in immunofluorescent staining of skin in SLE patient?

liquefaction of epidermal basal layer with vasculitis

- above line is epidermis
- below line is dermis (BM / basal layer of the epidermis)

What is the result of SLE on the kidney?

renal lesions

1. minimal / no detecable Ab
2. mesangial lupus nephritis

3. diffuse proliferative glomerulonephritis

4. membranous glomerulonephritis

What is the diffuse proliferative glomerulonephritis?

type IV
most common and worst prognosis for SLE patients
- causes nephrotic syndrome = compression on capillaries = HTN and hematuria

Membranous Glomerulonephritis (Wire loop)
- HSR type
- pathogenesis

loops are open but the walls of the loops are thick due to complement and IG deposition

thickening of BM --> nephrotic syndrome

What is the classic appearance on immunofluorescence of the glomerulus undergoing glomerulonephritis?

- give an Ex of disease

granular/lumpy-bumpy appearance

- outline the capillaries

- Ig and complement are lit up

Ex: good pasture syndrome (Type IV)

Which is the only syndrome associated with glomerulonephritis that has linear immunofluorescence?

good pasture syndrome

- seen in young males

What is the effect of SLE on the cardiovascular system?
- what will be a clinical feature

primarily = pericarditis = usually fibrinous pericarditis
- "friction rub" on auscultation

- myocarditis
- endocarditis (Libman-sacks) -- vegetations on both side of valve leaflet (anterior and posterior )

- Coronary artery disease

SLE effect on joints:

nonerosive synovitis

- joint pain but no joint deformity

(Rheumatoid arthritis also joint with no deformity )

SLE is an example of what type of hypersensitivity

Type 2 HSV presentations (hematological effects)

Other effects: Type III HSR

Clinical course of SLE (chronic history)

variable presentation
renal involvement

characterized by flare-ups and remissions

exacerbation associated with hypocomplementemia + treated with corticosteroids

What is the most common cause of death in SLE patient?

renal failure and recurrent infections (between flare ups)

Variant of Systemic erythematous

1. discoid lupus erythematous - negative dsDNA ab test, plaque-like skin lesion and visceral involvement

2. drug induced lupus: positive ANA, negative dsDNA

Drugs that are associated with drug-induced lupus:

- RX?

Procainamide (arrythmia)

Hydralazine (HTN)

Rx: stop giving the drug!!!

Sjorgen syndrome is the results of:

lymphocytic infiltration and fibrosis of the lacrimal and salivary glands

- unilateral or bilateral swelling by the mandible or angle of the jaw

Primary form of Sjogren's Syndrome presents with:

dry mouth (xerostomia) and dry eyes

Secondary form of Sjogren's syndrome is:

rheumatoid arthritits
- seen in 75% of patients

serological markers that are seen in 90% of Sjogren's patients:

SS-A (Ro) and SS-B(La)

What is the typical demographic for Sjogren syndrome?

older women
- 50s to 60s

(much older than Lupus)

What can result is the tears do not protect the cornea?

Keratoconjunctivitis
- gets scarred

Dryness of the mouth caused by reduction of saliva

____ gland is enlarged in half patients with Sjogren's syndrome

Do patient's with Sjogren have any other disease presentations?

most commonly another autoimmune disease (rheumatoid arthritis)

Mikulicz syndrome

lacrimal and salivary gland inflammatory involvement

Mikulicz disease

lacrimal and salivary gland enlargement (like is Sarcoidosis or lymphomas)

Biopsy of the lip is essential for diagnosis of which disease? why?

Sjogren

- looking for salivary gland involvement

There is an increased risk for development of ______ in Sjogren

marginal zone lymphoma (MALToma)

How can a MALToma be treated and which infection is it associated with?

Steroids
- H. pylori

Histological biopsy of the parotid in Sjogren's

corners = normal tissue; middle = problem of lymphocytes attacks the large and small ducts

If there are atrophic ducts being attacked by lymphocytes in Sjogren's the CT present will eventually be:

What is scleroderma (systemic sclerosis)?

fibrosis in skin and multiple organs

What are the 2 major categories of scleroderma, and what syndrome is associated?

1. diffuse
2. limited

- CREST syndrome

What is a trigger for excessive fibrosis?

abnormal immune responses and vascular damage

Autoantibodies that are found in patient's with Scleroderma:

1. ANA (screen)
2. anti-Scl-70 (diffuse form)
3. anti-centrometric (CREST syndrome)

What is the morphology of the limited form of Scleroderma (CREST)

CREST syndrome
1. calcinosis
2. Raynaud phenomenon

3. Esophageal dysmotility (dysphagia)

4. Sclerodactyly

5. Telangiectasia (dilation small vessels)

Morphology of the diffuse form of Scleroderma:

worse prognosis than CREST
1. thinning of epidermis
2. GE reflux
3. kidney - obliterate lume --> malignant HTN
4. Lung interstitial fibrosis
5. heart = pericarditis with effusion.myocardial fibrosis

What is the pathogenesis of the development of malignant HTN in patient's with diffuse Scleroderma?

obliterating the lumen in kidney --> decrease blood flow to the JG cells (tricking body that there is low blood volume/ hypotension) --> MALIGNANT HTN
because blocking the larger blood vessels (benign in Lupus)

A patient with scleroderma will complain of:

tightness in skin; lack of appendages (no hair follicles)
- microstomia
- autoamputation (falls off on its own)

Dermis with no appendages, will have thinned out bundles of __, which makes the histology similar to that of a ____.

collagen

- keloid

Clinical features of diffuse Scleroderma:
- demographic
- presentation
- manifestation

- primarily seen in women; peak in 50-60 age group

- Raynaud phenomenon, dysphagia, respiratory difficulties, arrhythmias, cardiac failure

- ominous manifestation: malignant HTN with subsequent renal failure

What is the typical demographic for a primary immunodeficiency?

X-linked Bruton Agammaglobulinemia
- gene mutation
- age manifestation
- risk
- absence of:

BTK gene = no pre-B cell differentiation

males at ~6 mo. when maternal Ig depleted

recurrent pyogenic bacterial infection

Absent: - germinal centers
- plasma cells throughout the body

What type of infection can patient's with X-linked Bruton agammaglobulinemia handle?

viral fungal infections since they have intact T-cell immunity

Which bacterial infections are Agammaglobulinemia patients most frequently infected with?

Strep, Staph, Haemophilus

Common Variable Immunodeficiency (CVID)
- mutation
- onset
- risk

hypogammaglobulinemia -- B cells fail to mature to plasma cells
- B cells become hyperplastic to try to make more plasma cells

Defective CD4

onset childhood/adolescence

increased incidence of autoimmune disorder

Isolated IgA deficiency:
- characteristic
- demographic
- Sign/sx
- risk

most common of all primary immunodeficiency disorders

- European descent (Caucasian)

- failure of selective IgA B cells to become plasma cells

- recurrent sinopulmonary infections + diarrhea
most are asymptomatic

anaphylaxis to IgA-containing blood products (transfusion from rare donor pool)

DiGeorge Syndrome (Thymic Hypoplasia)
- mutations
- lacking:
- results
- susceptibility

- undeveloped 3rd and 4th pharyngeal pouches (abnormal facies, thymic and parathyroid hypoplasia)

= selective deficiency of T cells

susceptible to viral fungal infections

SCID
- defect
- susceptibility
- inheritance

defect in humoral immunity/T-cell immunity

- bacterial, viral, fungal infections

AR and X-linked

AR manifestations of SCID:

ADA deficiency --> accumulation of toxic products in B and T cells = defective lymphocyte function

X-linked manifestations of SCID:

50%
associated with mutation

SCID is associated with a mutation that affects a protein shared by the receptors for :

IL-2, IL-4, and IL-7

What the main treatment for patient's with SCID:

- what is a possible complication

bone marrow transplant

- complication = graft vs. host disease

acquired immunodeficiency syndrome (AIDS)
- cause
- demographics

caused by retrovirus (ssRNA; reverse transcriptase) of the lentivirus family

- caused by HIV 1 and 2

homosexual, IVDU, contaminated blood products, hemophiliacs, passage of virus from mom to baby (parturition, breast milk, transplacental)

With the HIV-1 infection being a possible cause of AIDS, the virus has to have___ entry

CD4 T cells have an affinity to which receptor in AIDS?

gp120
- infective receptor with high affinity

Which cells in HIV are responsible for latency period?

macrophages and follicular dendritic cells

Macrophages are used to transport the HIV virus to:

Screening test and confirmatory tests for AIDs:

screening is ELISA - test for Abs (3-7 weeks for enough ab to be produced)

confirm: Western Blot to look for the viral particles

With an inversion of CD4:CD8 ratio, how can the CD4 cells die:

- results in CD4 count going down

PIC

1. cytopathic effect of virus

2. apoptosis

3. killing by CTLs

Acute phase of viral-host interaction in HIV/AIDs:
- Sx
- CD4 count
- viral replication levels

initial 6-12 weeks
high viral replication
- CD4 count going down
- asymptomatic/nonspecific symptoms

Chronic phase of HIV/AIDs
- Sx
- CD4 count
- viral replication levels

Cd4 cells that are infected migrate to the lymph nodes

months = years
low level viral replication

asymptomatic/lymphadenopathy

Crisis stage of AIDs
- Sx
- CD4 count
- viral replication levels

increased viral replication with decreased CD4 count (<200)
- long lasting fatigue, weight loss, diarrhea (STDs help the virus)

macrophages release the virus

What are differentials that can be associated with AIDs?

HIV
Reactive TB
Hodgkin Lymphoma

Patient with full blown AIDS is susceptible to:
-Sx

opportunistic infections

- respiratory infection
-blindness
- fungal infection from pigeon droppings

- cat feces
diarrhea (Cryptosporidium)

What is the oral lesions that are seen in a patient with AIDs

- What is a more severe form that can result in?

oral candidiasis (scrapes off )

Leukoplakia: white patches involving the oral mucosa --> squamous cell carcinoma of oral cavity

Candidasis can disseminated and cause:

esophageal candidiasis
- more severe

Kaposi's sarcoma
- association
- demographics

associated with AIDs in aggressive and metastasis

- associated with Herpes type 8

- homosexual =/bisexual males

Multiple KS lesions
involving the liver/stomach
- begins where

biopsy of Kaposi's lesion

sarcoma so it should be spindle shaped

extravasation of RBCs (not in true blood vessels

Non-Hodgkin's Lymphoma
- virus-associated

high grade B cell lymphoma

- seen in brain

- associated with EBV

Carcinoma of the cervix:
- viral association
- what is seen in homosexual/bisexual patients

HPV

see squamous cell carcinoma of anus associated with HPV

Neurologic disease/ Sx associated with AIDs:

meningoencephalitis
aspectic meningitis
vacuolar myelopathy
peripheral neuropathies
AIDs-dementia complex

AIDS complications

MAI
CMV = blindness/retinitis

Amyloidosis
- characterisitcs

eosinophilic extracellular protein that builds up in organs = dysfunction

Congo red stain

Amyloidosis

- pink with this stain

If you put congo red stain under polarizing light, what is the appearance?

apple green birefringence

The best way to monitor patients with AIDs is using:

the viral load
- better indicator of the CD4 levels

Pathogenesis of amyloidosis
- what are the 2 major types:

1. AL
- amyloid of light chains

2. AA- amyloid association

Amyloidosis: AL

1. Plasma cell dyscrasia : causing deposition of protein derived from immunoglobulin light chains
2. Associated with multiple myeloma : Bence Jones proteins

Amyloidosis
AA (secondary):

chronic inflammatory condition like TB or rheumatoid arthritis

- liver will start kicking out amyloid as phase response for buildup

Kappa or lambda light chain derived

- associated with immune dyscrasia (primary)

non-immune globulin; associated with chronic infection (secondary type)

Localized dialysis-associated amyloidosis from beta-2-microglobulin (from MHC-1); usually presents as carpal tunnel syndrome (or other joints/tendon sheaths)

seen in Alzheimer disease

seen in older patients
- systemic senile amyloidosis and familial amyloid neuropathies

Calcitonin- associated with medullary carcinoma of the thyroid

Parafollicular C cells make up this tumor and secrete calcitonin - amyloid produced

islet amyloid peptide, associated with type II diabetes

plaque accumulation, can get so large the patient cannot breathe

Congo red stain in the liver of a patient with amyloidosis

amyloid deposits in blood vessels

- involves the space of disse (between hepatocytes and sinusoids)

ito cells (associated with vit A) found there

Amyloid under polarized light:

- since stained with congo red, the light will present the tissue as apple green with birefringence

Congo red biopsy of the kidney:

- deposits in the glomeruli involves the BM --> nephrotic syndrome

- albumin coming out = edema

nephritic syndrome:

compression of blood vessels

Apple green birefringence occurs:

under polarized light after tissue is stained with congo red

- glomerulus and other blood vessels

Clinical features of amyloid:
- tongue
- heart
- kidney
- GI tract

Demographics?

tongue: macroglossia

heart: restrictive cardiomyopathy

kidney: nephrotic syndrome

GI: malabsorption

Demographics:
- over 50 y/o

If you suspect that the amyloid is systemic, what should you biopsy?

abdominal fat, anal area (easy access)

What is the vaso vasorum?

small vessel networks that supply the outer media of large arteries

What are characteristics of elastic arteries?

high elastin content of the media
- allows blood to be propelled throughout the body
- if less compliant = raises systolic blood pressure (expand in systole + recoil in diastole)

What are characteristics of a muscular artery?

smooth muscle
responds to autonomic and metabolic factors --> vasoconstriction or vasodilation
= regulates regional blood flow and blood pressure

Small artery and arteriolar function

within tissues and organs
control blood flow to capillaries

Capillaries are ideal for:

What is the histological presentation of a small muscular artery?

reduced media thickness
- in tissue and organs

What the histological appearance of an arteriole?

1-2 layers of smooth muscle
- controls flow to capillaries

___ flowing through the capillary

Venous circulation carries ____ of the blood volume

veins with thinner, and less ridged walls =

compression, infiltration by inflammation and tumors

Reverse in blood flow is prevented by:

liver and renal endothelial cells are =

fenestrated for filtration

How do endothelial cells regulate resistance?

by regulating smooth muscle tone

What are some factors that can influence the endothelial cell regulation

drugs
virus
cytokines

During anaphylaxis, mast cells cause:

endothelial cytoplasm contraction

What can occur after endothelial cytoplasms contraction has taken place?

intravascular fluid moves to extravascular space = edema = reversible (no injury)

blood pressure (BP) measures:

systolic (max pressure) /diastolic (minimum)

During HTN, the arterioles are:

a point of principal resistance to blood flow

If you 1/2 the diameter, what is the effect on resistance?

increases resistance by 16-fold

Sustained diastolic pressures above ____mmHg or sustained systolic pressure above ____mmHg are associated with increased risk of atherosclerotic disease

89 mmHg; 139 mmHg

140/90

Threshold for patients at risk of cardiovascular disease?

there is no rigidly defined threshold

Increased pressure in a patient, will result in:

increased risk and detrimental effects

HTN can be asymptomatic and remain clinically silent for years, what are other symptoms that can be a sign?

headache, vision changes, chest pain, nosebleed

What are secondary effects that HTN can lead to?

- risks?

LV hypertrophy, cardiac failure, cardiac failure, benign nephrosclerosis

Risk: ischemic heart disease, stroke

What percentage of HTN is idiopathic?

- what are other names for idiopathic HTN?

85-95% idiopathic

AKA essential/primary HTN (cause unknown)

Secondary HTN is related to which processes?

renal or adrenal disease, renal artery stenosis, or other identifiable causes, genetic

If Primary (Essential) Hypertension is untreated it can result in:

hypertensive retinopathy -- flame hemorrhages

cotton wool spots "copper wiring" -- "AV nicking" and papilla edema

headaches

Genetic factors that contribute to primary/essential HTN?

- demographic common

decreased sodium excretion = increasing systolic + diastolic BP

- more common in black Americans than white Americans

What are potential effects of HTN on the heart?

1. ventricular hypertrophy
2. reduced CO due to less BV in ventricle (end diastole) = increased atrium P and V

3. can lead to kidney damage
4. heart failure and myocardial infarctions

Which cells produce renin and where?

JG cells
- around glomerular afferent arterioles

Renin is released in response to:

1. low BP
2. low Na+ levels

* increased Na+ resorption

Which enzyme leaves plasma angiotensinogen to angiotensin I?

Angiontensin II function:

1. vasoconstriction
2. stimulate aldosterone secretion
3. tubular sodium resorption

goal: retain fluid

function of aldosterone is to

inhibit sodium resorption = excretion = diuresis

- systemic vasodilation = lower BP

Function of aldosterone is to

increase sodium absorption (and water with it)

Primary aldosteronism
aka..
- cause
- effects
- Sx:

Conn's syndrome

adenoma in adrenal cortex

Sx: hypernatremia, hypokalemia, increased BP

shuts off RAAS = low plasma renin

Hypoaldosteronism
- effects on urine
- serum levels
-

"salt wasting"

hyponatremia --> hyperkalemia

increased urine sodium and decreased urine potassium

water follows salt = hypotension

What is malignant HTN?
- BP value indicating this
- common predisposition
- prognosis
- kidney appearance

rapidly rising pressure, usually young African American males

200/120

- usually in patients with pre-existing HTN

death within 1-2 yrs = CHF, renal failure, CVA

"flea-bitten kidney"

What are the 2 types of atherosclerosis?

1. hyaline
2. hyperplastic

Hyaline atherosclerosis:

hyaline thickening in arteriolar walls from increased protein deposition

(hyaline deposition in arteriole wall)

What are causes of hyaline atherosclerosis?

1. long standing HTN
2. diabetes

Hyperplastic Atherosclerosis
- results in
- caused by

caused by malignant HTN

results in:
- malignant nephrosclerosis "flea bitten kidney"

An acute increase in BP in a patient with malignant HTN is caused by:

basement membrane duplication/smooth muscle hyperplasia

What are the 2 types of histological presentation of hyperplastic atherosclerosis?

1. fibrinoid necrosis (fibrin deposits in vessel wall)

2. hyperplastic arterioles "onion skin" appearance of arterioles

Hyperplastic atherosclerosis can also be described as

necrotizing arteriolitis

What are some causes of secondary HTN?

1. adrenal- hyperaldosteronism (Conn)

2. Renal- atherosclerosis/stenosis

** 3. renal artery stenosis

4. aortic coarctation
5. drugs
6. pregnancy
7. pheochromocytoma

Effects of secondary HTN caused by renal- atherosclerosis/stenosis:

reduced BF = increased renin
- increased BP

The most common cause of secondary HTN:

Renal artery stenosis

What is the effect of aortic coarctation on BP?

decreased BF to the kidneys = increased Renin = decreased aortic elasticity

increased BP above coarctation

A common cause of HTN in young women is:

drugs
- oral contraceptive increase angiotensin

Types of arteriosclerosis

1. Monckeberg medial sclerosis
2. Arteriolosclerosis
3. Atherosclerosis

Monckeberg medial sclerosis

usually found in radial/ulnar artery

- calcification of muscular arteries (not cause of stenosis)
- no clinical significance, older patients

- dark purple = calcification

Ateriolosclerosis

small artery/arteriole disease

thickening and narrowing of lumen - ischemia with HTN

1. hyaline
2. hyperplastic

Atherosclerosis
- complications

intimal fibrofatty plaque = atheroma

complications:
ischemic heart disease (IHD) with MI, strokes, gangrene of extremities

50% of deaths in western world

Framingham Heart Study (1948)

Longitudinal cohort study designed to identify risk factors associated with cardiovascular disease
-Term "risk factor" was popularized after repeated use in this study

Risk factors for ischemic heart disease (IHD)
- why they are risk factors

1. age
2. gender
before menopause-estrogen protective

after menopause - loss of protective estrogen = major risk increase = atherosclerosis related disease increase = catch up to men

3. genetics - most important risk factor
- family history of hypercholesterolemia, HTN, diabetes

LDL vs. HDL
- function

LDL = bad cholesterol; transports cholesterol to tissues

HDL = good cholesterol; mobilizes cholesterol from plaques

If there is increased serum cholesterol or LDL, what is the risk of atherosclerosis?

increased risk of atherosclerosis

If there is an increased HDL, what is the associated risk with atherosclerosis?

decreased risk of atherosclerosis

Modifiable risk factors for ischemic heart disease:

1. hyperlipidemia
2. HTN
3. DM
4. smoking
5. lack of physical activity
6. stressful life (type A)
7. use of oral contraceptives

C-reactive protein (CRP)
- what does it assess
- marker for:

good test to perform for risk assessment
- circulating marker of inflammation

20% of all heart disease events occur in the absence of

known risk factors

What does the vascular response to injury cause?

thickening of the intima = stenosis and vascular obstruction

How does thickening of the intima occur in vascular injury?

1. smooth muscle proliferation
2. matrix deposition
3. intima thickening

What is the earliest event/trigger for atherosclerosis?

Earliest pathological change of atherosclerosis?

dysfunction from endothelial injury
(not seen but present)

intimal thickening- earliest thing that can can be seen with a microscope

Pathogenesis of atherosclerosis is characterized by:

intimal plaque thickening (atheroma) and weakening of underlying media

Endothelial injury leads to what in the vessel wall?

leukocyte adhesion and vascular permeability

What is the role of cytokines during endothelial injury?

call the smooth muscle cells to the intima

Which cells engulf lipid (oxidized LDL) during atherosclerotic formation?

macrophages and smooth muscle

Oxidation of LDL by which cells can cause the formation of foam cells?

macrophages and smooth muscle cells

LDL is needed to create the foam cells

Collagen and ECM is deposited in the wall by:
- which one only creates ECM?

smooth muscle cells

- only smooth muscles create ECM

Major components of an atherosclerotic plaque

1. fibrous cap
2. necrotic center (constantly changing, not always present)
3. media

2 stages of an atherosclerotic plaque

1. Fatty streak (reversible) = earliest intimal thickening
- intimal aggregation of foam cells (macrophage only at this point)

2. Atheromatous plaques = intimal thickening and lipid accumulation

3 parts of atheromatous plaques:

1. Cells - smooth muscle, macrophages, T cells

2. ECM - collagen, elastic fibers and proteoglycans

3. Lipids -

Are fatty streaks reversible or irreversible?

reversible
- first noticeable sign of damage of foamy macrophages

Mild atherosclerosis features:

smooth muscle hyperplasia, some lipid deposition in atheroma/plaque

- commonly in aorta

Clot disruption in atherosclerosis can cause

Severe atherosclerosis
- demographics

plaque formations are normally seen in patients who are in 70s-80s who may not have other risk factors

Most common location of atherosclerosis:

abdominal aorta

Complications that can occur from atherosclerosis:

1. vessel occlusion/thrombosis

2. HTN from renal artery stenosis (RAAS- secondary HTN)

3. peripheral vascular disease (PVD)

What are symptoms associated with peripheral vascular disease?

Claudication = pain, weakness, numbness, cramping with activity (indication of atherosclerosis)

- Acute peripheral artery occlusion sx (5P's)
pain, pallor, paraesthesia, paralysis, pulseless

ischemic necrosis - gangrene

vessel weakness
cerebral atrophy (circle of willis)
atheroembolism (release debris into blood stream)

What is the most common atherosclerosis clinical disease?

abdominal aorta - large elastic arteries are most affected

When is atherosclerosis classified as critical stenosis?

70% decrease of lumen cross-sectional area
- chest pain with exertion = stable angina

What are the 2 types of plaques:

1. stable plaque:
- increased smooth muscle cells = extracellular matrix

2. unstable plaque:
- increased inflammatory cells = breakdown matrix

Components of an atherosclerotic stable plaque:
- histology
- clinical presentation of patient

fibrous cap
necrotic core with cholesterol clefts

Not acute changes, but pain with exertion/increased demands

not meeting increased O2 demand (with exertion)

"stable angina"

Acute change of unstable plaque:

1. plaque erosion/rupture = partial/complete vascular thrombosis
- MI/Cerebral infarct

2. acute plaque change = sudden onset
- rupture/fissuring
- erosion/ulceration
- hemorrhage into atheroma

Histological features of an unstable/complicated plaque

-sudden outcomes

thin caps, large lipid cores, dense inflammation

sudden and fatal outcomes:
- acute plaque rupture
- thrombosis
- embolization

MI and death

What are aneurysms?

- most important causes?

localized abnormal dilation of the blood vessel/heart

1. atherosclerosis
2. HTN

What are the morphological types of aneurysms?

1. fusiform
- ovoid configuration/circumferential dilation

2. saccular
- bubble-out pouching "berry aneurysm"

3. Dissecting
- column of blood separating media (aortic dissection, tunnels between layers of wall)

vessel wall intact or thinned ventricle wall of heart

defect in the wall causing blood to collect outside the vessel

- bound by extravascular tissue

Atherosclerotic aneurysm location

predominantly abdominal aorta

Syphilitic aneurysm location

ascending and arch of aorta (tertiary syphilis)

Berry aneurysm location
- disease association?

cerebral arteries at circle of willis

- associated with polycystic kidney disease

Mycotic aneurysm:

damage of the wall of any blood vessel by infectious agents

Hypertensive aneurysm location

ascending or thoracic aorta

Abdominal aortic aneurysm is due to:

- usually located at
- demographic
- clinical presentation

atherosclerosis
- medial destruction of vessel

located usually below renal arteries and above the bifurcation of iliac

over 50, usually males, more commonly smokers

Clinical: abdominal bruits/pulsatile mass
- new onset of cold, pale lower limb = atheroembolism of AAA

How are AAA discovered?

clinical presentation suggestive?

normally asymptomatic

pulsating abdominal mass/bruit

can present as low back pain/abdominal pain

- embolism form atheroma/mural thrombus to extremities or kidney

In a AAA what is the rupture triad?

sudden severe left flank pain, hypotension, pulsatile mass

Thoracic aortic aneurysm
- causes
- disease associated
- Sx

usually due to HTN

Marfan's syndrome - idiopathic cystic medial necrosis

SX:
- respiratory difficulties
- difficulty swallowing
- cough due to compression of laryngeal nerve

Syphilitic aneurysm/aortitis is a complication from:

tertiary syphilis (Treponema pallidium)

What does treponema pallidium infect?

vaso vasorum of the ascending and transverse aorta

Vasculitis is called ____ which will lead to ___

endarteritis obliterans ; medial necrosis

Weakness and dilation of the aorta wall and valve ring will lead to which cardiac features?

left ventricular overload and hypertrophy

What is it called when there is irregular intimal wrinkling and scarring from inflammation?

tree bark / syphilitic aortitis

Berry aneurysm
- what it is
- location
- most common

saccular dilation usually around circle of willis and base of brain
- junction of communicating branes with the anterior cerebral artery (ACA)

Why is there a risk with junction of communicating with main cerebrals?

no internal elastic lamina/smooth muscle of the split/junction '

has area of natural weakness = vulnerable to increased tension

What is the classic onset of a berry aneurysm?
- which disease process is it normally associated with?

"worst headache i have ever had"

- associated with polycystic kidney disease

What is a dissecting aneurysm of the aorta? (dissecting hematoma/aortic dissection)

false aneurysm with intimal tear allowing blood to enter media

An intimal tear is secondary to:

1. HTN - increased pressure + poor vascular perfusion= medial degeneration

2. Marfan Syndrome
- idiopathic medial necrosis = weakness from Marfan's pathology

Mechanism of a dissecting aneurysm of aorta:

1. cystic medial degeneration (HTN, Marfan's, pregnancy)

medial ischemia = increased ground substance = medial "degeneration"

Major risk factor of dissecting aortic aneurysm:

**HTN**
- atherosclerosis is risk factor

Marfan syndrome, Ehlers Danlos

Clinical Sx of dissecting aortic aneurysm:

severe "ripping" pain in anterior chest radiating to back

new onset of diastolic murmur of aortic insufficiency = dissection near heart/aortic valve

widened mediastinum on CXR

hypotension bad sign

Where are most aortic dissections talking place
- types
- common cause of death

most proximal ascending (worst) with/without descending aorta involvement (type A)

Type B = distal to subclavian

common cause of death = pericardial tamponade-- rupture through adventitia into surrounding cavity

What can an aortic dissection also cause?

aortic insufficiency
- new diastolic murmur
- MI
- ischemia of bowel, limbs

Type B aortic dissection
- location

distal to subclavian

What is getting damaged in the aorta during a type A aortic dissection?

dissection and hemorrhage in false lumen

cusps of aortic valve rupture

opened aorta

What is seen on the histology of an aortic dissection?

- false lumen created between media layers

- true aortic lumen

Prognosis of an aortic dissection

50% die within 48 hours
-2 week undiagnosed dissection = 75% mortality rate

Vasculitis
- types

inflammation of the vessel wall

1. immune mediated
2. infectious
3. physical and chemical injury

Clinical manifestations of vasculitis:

fever, myalgia, arthralgia, malaise

rash, petechiae, purpura

Immune mediated vasculitis mechanisms:

1. immune complex deposition (lupus, Hep B, Hep C)

2. Anti-endothelial cell Abs

3. Anti-neutrophil cytoplasmic antibodies

Immune complex deposition
- HSR
- disorders associated

type 3

- SLE, Henoch-Schoenlein purpura, cryoglobulins

drug hypersensitivities and infections

Anti-endothelial cell antibodies:
- HSR
- diseases associated

Type II HSR

1. Kawasaki disease - Ab to vascular endothelial cells

2. Good-pasture = Ab to BM

Anti-neutrophil cytoplasmic antibodies:
- what Abs react to
- cells involved

pts with vasculitis have circulating Ans that react with neutrophil cytoplasmic Ags

"ANCAS"

activate neutrophils = inflammation = endothelial cell damage

Vasculitides:
Anti-proteinase-3
- aka

PRS-ANCA previously c-ANCA

Wegener's granulomatous = granulomatous with polyangitis

Anti-myeloperoxidase

MPO-ANCA/p-ANCA

- microscopic polyangitis
- Churg-Strauss syndrome

Is polyateritis nodosa ANCA (+) ?
- association

red herring
NOT (+)

Which vessels does polyarteritis affect?

small and medium
- classified under medium vessel disease

Which diseases are classified under large vessel disease?

- histo appearance

1. Temporal Arteritis
2. Takayasu Arteritis

Wegener's Granulomatous

*Granulomatous on histo

Temporal Arteritis
- demographic
- location
- risk if untreated

most common form of vasculitis in elderly of U.S/Europe

- Segmental larger artery vasculitis, involving temporal and other cranial arteries = arteries of the head

Untreated = can lead to blindness - emergency!

Clinical presentation of temporal arteritis/giant cell arteritis:

throbbing headache (no response to NSAIDs)

tender temporal area, firm, nodular temporal artery
- visual disturbances (double vision)
- Jaw claudication
- polymyalgia rheumatica (proximal joint pain, morning stiffness)

Histology of temporal arteritis/giant cell arteritis:

segmental granulomas with giant cells and intimal fibrosis of vessel wall

- multi nucleated giant cells, histiocytes, lymphocytes

- negative results DOES NOT exclude diagnosis

Takayasu Arteritis
- demographic
- vessel involvement
- Clinical

demo: Asian women (japan) under 40 y/o

involve: large vessel; aortic arch and its major arches

Clinical:
diminished radial pulse -- subclavian artery affected (cold arms, discrepant BP between arms)

Histology of Takayasu arteritis

Granulomatous vasculitis
- extensive intimal fibrosis

NEED CLINICAL

Polyarteritis Nodosa (PAN)
- clinical
- diseases associated

Clinical:
medium to small sized arteries
exception = does not involve lungs

Renal disease- HTN = causes more deaths

Tender subcutaneous nodules and "palpable purpura"

most common = abdominal pain and mononeuritis multiplex

Polyarteritis nodosa (PAN)
- risks if untreated
- demographic
- 30% of cases associated with:

untreated = fatal = die from renal failure

common in young males

Hepatitis B surface antigen

What is the association of Hep B with PAN?

causes immune complex deposition

- can be P-ANCA positive = red herring -

drug abusers increased incidence (Hep B and C)

Polyarteritis Nodosa (PAN)
- histology

segmental, transmural. (full wall thickness) inflammation
aneurysmal nodules

fibrinoid necrosis and neutrophilic infiltrate

variable morphology/stage in the same blood vessel*** PAN FEATURE

Kawasaki disease

most common cause of acquired heart disease in children

COVID 19 causes similar vasculitis in children

"mucocutaneous lymph node syndrome"

Clinical manifestations of Kawasaki disease:

high fever for more than 5 days

red/patchy red palms and sole = peeling, genital area

conjunctivitis
"strawberry tongue"

*** Significant because of coronary vessel involvement = aneurysm

Pathogenesis of Kawasaki disease:

coronary arteries are frequently involved with aneurysm formation

1-2% die

Thromboangitis Obliterans
(Buerger disease)
- demographic
- vessels involved
- early vs advanced stage
- Histology

Rx:

demo: middle aged heavy smokers

vessels: artery, vein, perineural sheath
- tibial and radial arteries

early: intermittent claudication
late: gangrene

Histo: abscess formation in vessel

Rx: cessation of smoking

If patient has a history of intermittent claudication:
- disease
- what other associated clinical manifestations

Thromboangitis obliterans. (Buergers)

+ loss of tips of fingers or toes with bone sticking out - gangrene

Microscopic polyangitis
- sites
- presentation
- which ANCA

multiple sites, non-specific

palpable purpura on skin
lesions are the same age

***Associated with p-ANCA (MPO-ANCA)

Clinical pf microscopic polyangitis/polyarteritis:

palpable purpura
hemoptysis = cough = can be life threatening

hematuria
proteinuria - kidney inflammation = rapidly progressive glomerulonephritis

Recent new drug prescribed:

microscopic arteritis/polyangitis

Histology of polyangitis/polyarteritis

leukocytoclastic vasculitis

fibrinoid necrosis of vessel wall

nuclear dust and debris (necrotizing)

Wegener's granulomatosis
- classic sites affected
- ANCA associated

1. URT
2. LRT
3. Kidneys - renal failure

C-ANCA (PR3-ANCA)
- high sensitivity/specificity; NOT definitive

Clinical presentations of Wegener Granulomatosis:
- damage from chronic?
- Rx:

sinusitis
otitis media
nasal ulceration
eye inflammation

- URT Sx is what sets it apart from other vasculitides

chronic inflammation can cause destruction of cartilage, lung hemorrhage

Rx: steroids

Histology triad in Wegener's Granulomatous

1. necrotizing vasculitis

2. necrotizing granulomas in surrounding tissue (not vessel wall)

3. large areas of necrosis (geographic necrosis)

95% have PR3- ANCA (c-ANCA)

Churg-Strauss Syndrome
- aka
- vessel
- triad of presentation
- if cardiac involed?

eosinophilic granulomatous with polyangitis

small vessel necrotizing vasculitis

triad:
- asthma: lung infiltrates
- allergic rhinitis
- peripheral hypereosinophilia

heart (cardiomyopathy) in 60% and accounts for 1/2 of deaths from disease

MPO-ANCA in 1/2 of cases (p-ANCA)

Leukocytoclastic vasculitis
- disease
- histo features

- Churg-Strauss Syndrome

hypereosinophilia

Henoch-Schonlein Purpura

idiopathic disease of children often preceded by URT infection

clinical:
- hematuria
- purpura -- legs, buttocks, knees
- abdominal pain

immune complexes with IgA deposits in wall of affected blood vessels

Behcet's disease
- clinical presentation
- HLA involved

1. oral ulcers
2. genital ulcers
3. uveitis

associated with HLA-B51

Hypersensitivity Vasculitis
- mediated by:
- what is it
- histology

immune complex mediated

acute inflammation of small vessels (purpura, glomeruli and GI may be involved)

Histo: leukocytoclastic vasculitis

A drug vasculitis is considered:

a hypersensitivity vasculitis

Connective tissue disease vasculitis such as ____ are considered ____ vasculitis

SLE, Sjogren's;
Hypersensitivity vasculitis

Microscopic polyangitis is a separate category of which ANCA?

MPO-ANCA (p-ANCA related)

Causes of microscopic polyangitis:

1. medications
2. infection
3. collagen vascular disease (lupus)
4. malignancy
5. 50% are idiopathic

Raynaud's phenomenon

exaggerated vasoconstriction of arteries and arterioles

pallor and cyanosis

red, white, and blue color changes from proximal to distal

Primary Raynaud's
- demographic
- characteristics
- sequelae

usually young women

symmetrical

can lead to atrophy -- ulceration and ischemic gangrene are RARE

Secondary Raynaud's phenomenon
- caused by
- presentation

vascular insufficiency caused by other diseases
(lupus, scleroderma, Buerger disease)

asymmetrical involvement

Varicose veins:
- characteristics
- clinical

abnormally dilated, tortuous veins

loss of vein wall support and valves incompetent with standing

Clinical: ;
- stasis, congestion, edema, pain, and thrombosis

creates chronic congestion = causes tissue ischemia

Varicose veins can secondarily cause __ dermatitis.

stasis dermatitis

"brawny induration"

Esophageal varices
- primary disease
- risk

varices that shunt the blood through veins at gastroesophageal junction

risk: can cause fatal hemorrhage -- need to consider in alcoholic = vomiting blood

Periumbilical shunting causes:

Hemorrhoids
- cause

pregnancy, straining to defecate

can bleed (bright red blood), thrombose and ulcerate

inflammation of a vein

Thrombophlebitis
- demographic

A blood clot forming in the inflamed superficial vein

common in ppt with varicose veins, pregnant, immobilization, IV and IV drug use

Deep vein thrombosis
- predispositions

deep leg veins: site of >90% of cases of DVT

1. prolonged immobilization

2.adenocarcinomas (via hypercoagulability)
- Trousseau sign = changes location
- most commonly pancreatic adenocarcinoma

DVT
- Sx
- complication

NO reliable signs/symptoms
- may have Homan sign/pain squeezing in calf

complication:
pulmonary embolism
~15% of sudden deaths

Superior vena cava syndrome

dilation of veins of head, neck, and arms with cyanosis

via tumor/growth

Inferior vena cava syndrome

renal and hepatic carcinomas like to invade IVC

- lower extremity edema, distended and superficial abdominal veins and proteinuria if renal involved

Lymphangitis
- what it is
- common causative agents
- clinical
- complication

acute inflammation elicited when bacterial infection spread into lymphatics

common agents: group A B-hemolytic streptococci

Clinical:
- red, painful subcutaneous streaks (inflamed lymphatics)
- painful enlargement of draining lymph nodes (acute lymphadenitis)

complications:
- sepsis (vessels)
- cellulitis, abscess (tissues)

Lymphedema
- primary
- secondary + causes/results

- persistant edema = ?

primary = genetic

secondary = obstructive
- surgical procedures that remove groups of lymph nodes
= filariasis

- fluid accumulation + edema

persistant edema = peau d'orange (inflammatory breast cancer)

Lymphedema from filariasis aka

- where is fluid accumulating?

elephantiasis

unilateral leg edema

Birthmark
(Regress spontaneously)

Port-Wine Stain (Nevus Flammeus)
- results in

enlarge and thicken - do not regress

results: trigeminal nerve distribution = sturge-weber syndrome

- vascular abnormalities, seizures, mental retardation, hemiplegia

Spider telangiectasia

associated with pregnancy and liver cirrhosis = blanch when pressed

Osler-weber-rendu syndrome
- aka
- inheritance
- causes

hereditary hemorrhagic telangiectasia

AD

malformation of dilated capillaries and veins at birth

distribution: skin, mucosa, respiratory, GI tract

CAUSES EPISTAXIS (nose-bleeds)

Hemangioma
Pyogenic Granuloma
- characteristics

- rapidly growing
- can be from trauma

in skin, subcutaneous tissues, mucus membranes

Infantile hemangioma of children
- classified into:
- characteristics
- age

superficial = juvenile/strawberry hemangioma (damage if removed)

deep = large vascular spaces, can be in deep organ - cavernous hemangioma

grow rapidly for 18 months, regress by age 5-9

Congenital Hemangioma (CH)
- characteristics

rapidly involuting congenital hemangioma (RICH)

Non-involuting congenital hemangioma (NICH)

Hemangiomas can be associated with _________ disease:

Von Hipple Lindau disease

Bacillary Angiomatosis
- cause
- aka

opportunistic infection of immunocompromised persons caused by Bartonella genus (gram negative)

Bartonella henselae - cats "cat-scratch disease"

Bartonella quintana - live, caused french fever in WWI

How can you tell if an angioma is lymphatic?

simple lymphangioma

1-2 cm head and neck

Canvernous lymphangioma
- what syndrome is associated

cystic hygroma
- neck/axila of children = can get large and cause deformity

***Turner syndrome

Glomus tumors - "Glomangioma"
- what it is
- cells involved
- location

painful tumors arising from proliferation of glomus body smooth muscle cells

glomus cells - control thermoregulation

- found on distal digits - especially under fingernails

Kaposi sarcoma viral cause:

HHV-8
human herpes 8

Epidemic Kaposi's sarcoma

associated with AIDS
aggressive
- most common HIV malignancy 2-3% of HIV patients in US

Endemic Kaposi's Sarcoma

seen in africa

<40 yo
HIV negative

Epidemic + endemic Kaposi's makes KS most common tumor in ___

Classic Kaposi Sarcoma

indolent course/not aggressive - remain local to skin

older European men, Ashkenazi Jews, Mediterranean

NOT HIV related

transplant-associated kaposi sarcoma

- clinical

aggressive
solid organ transplants

Stages:
patches --> plaques --> nodules

Histology of Kaposi's sarcoma

spindle cells
- slit like spaces lined by variable atypical spindle cells with extravasation of RBCs

Angiosarcoma
- characteristics
- settings
- prognosis

highly malignant tumor from vascular endothelial cells

often on scalp of old men

Settings:
- lymphedema --> breast cancer

- radiation --> breast cancer

- chemical exposure - liver -> VAT

5 year survival ~30% BAD ACTOR

Clinical presentation of angiosarcoma

red papules/nodules

blend into tissue = hard to define/remove

Histology of angiosarcoma:

malignant spindle cells lining true vascular spaces

- very invasive into surrounding tissue

Liver angiosarcoma
- stain used
- associated

VAT of chemicals

- Vinyl chloride
- Arsenic
- Thorotrast

CD31 stain may be used to identify vessels

Cardiac output is defined as the amount of venous return to ___, since it is a ____ system.

right heart; closed system

How does blood flow through the body in terms of a gradient?

move down the pressure gradient

Which vessel is the area of greatest resistance? Why?

Arterioles

- protects capillaries and control regional blood flow

Since the arterioles have greatest resistance, what is required to maintain flow?

A drop in pressure

Since capillaries have a much larger surface area, what is the affect on blood flow?

Slows down flow for gas exchange

Large changes in pressure, proportionally cause an increase in...

flow

(2x ∆pressure = 2x flow)

Veins contain valves, which ensure:

blood return (if complaint and low resistance)

Controlling diameter of a vessel has a profound effect on what?

Examples?

blood flow

- Hypovolemic shock + Anaphylactic shock (vasodilation)

If the following changes are made to the vessel, what is the result?

2x radius = __ flow
2x radius = ___ resistance

1. 16x flow
2. 1/16 resistance

Veins are most compliant, and they hold how much of the blood supply?

What about if the veins are dilated?

hold 2/3 blood supply

if dilated, amount increases septic shock/anaphylactic shock

What disease process occurs in older patient as their arterial compliance decreases further and increased pressure?

Formula for BP:

Humoral factors that influence peripheral resistance:
1. constrictor examples
2. dilator examples

Constrictors:
- Angio II
- Catecholamines
- Thromboxane
- Leukotrienes
- Endothelin

Dilators:
- Prostaglandins
- Kinins
- NO

Neural factors that influence peripheral resistance:
1. Constrictors
2. Dilators

Constrictors:
- alpha-adrenergic

Dilators:
- beta-adrenergic

Controls vasoconstriction

Norepinephrine- Epinephrine- Angiotensin II - Aldosterone-
ADH/ Vasopressin -Thromboxane-

Controls Vasodilation

Prostacyclin-Adenosine-
Nitric oxide -Histamine-
Carbon Dioxide -Acetylcholine-
Atrial Natriuretic Peptide -
(+ water and salt excretion)

Preload

If there is increased preload, what happens to contractility?

volume of ventricle before contraction (stretch)

Increased contractility

Afterload

EX of diseases with increased afterload?

pressure/force the heart must work against to eject blood from the ventricle

HTN and aortic stenosis = increased afterload

Contractility

What factor can alter the contractility?

intrinsic strength/energy of cardiac muscle independent of preload

preload can alter contractility

If there is an increased venous return or increased ventricular EDV, what is the affect on stroke volume or cardiac output?

increased SV or CO

What is one way to increase preload that will not result in an increased cardiac output?

increased aortic pressure (increased afterload)

What are ways to increase preload?

1. increased atrial contractility
2. increased ventricular compliance
3. decreased HR
4. decreased venous compliance (vasoconstrict)

5. increased thoracic venous blood volume (respiration)

6. increased aortic pressure

Increased afterload = ___ cardiac work = ___ cardiac output

increased cardiac work; decreased cardiac output

Decreased afterload, will have what affect on the cardiac output, and why?

increased cardiac output

- less work required from the heart to eject blood

Decreased afterload = ___ cardiac work = ___ cardiac output

Decreased cardiac work; increased cardiac output

Boyle's law states that

the volume of a gas is inversely proportional to its pressure

(increased P = decreased V)

With an increased volume of the lungs, where does the air flow?

Flows in to the lower pressure lungs

is relaxation an active or passive process?

How is it possible for air to move from higher to lower pressure?

pleural surface seal created from the fluid in the pleural space

Inspiration __ the right atrium and right ventricle = what affect on the pressure?

expands RA and RV; dropping pressure

A drop in pressure during inspiration, pulls blood from ____ system into___.

venous system into the right heart

During isovolumetric relaxation, does the pulmonary valve or aortic valve close first?

aortic then pulmonary valve

- inspiration causing split of S2 (A2,P2) delaying closure of Pulmonic valve

During expiration, in which direction does everything get pulled?

towards the lungs

1. increased pulmonary flow/volume

2. transient decreased flow of blood from the lungs to LA

3. pull towards the lungs

What is happening in the left ventricle during inspiration?

filling decreases

During expiration:
lungs __ = ___ flow from lungs to LA = ___ left ventricular filling

deflate; increased flow; increased LV filling

What is the net effect of increase rate and depth of inspiration?

Increased left ventricular SV and CO

Respiration-Inhalation ___ blood flow to RA, due to...

what is happening to the left side of the heart in this case?

increases

due to pull of negative pressure in the lungs

Left side:
- decreased return to the left side of the heart for the same reason

Inspiration pulls blood towards the __

Why are right sided murmurs be increased with inspiration?

Why are left sided murmurs increased with expiration?

ex of auscultated murmur during exhalation

More volume into the left side

ex: aortic regurgitation (hold it)

Does vasoconstriction/vasodilation of the arterioles of the arterioles influence the venous return?

What will vasoconstriction of the arteriolar system due to venous return? Why?

decreases it; due to increased afterload and reduced cardiac output

Reduced output = ______

What is the effect of reduced afterload on CO and venous return?

increased cardiac output; increased venous return (VR)

Formula for cardiac output:

How can we compensated for reduced output?

1. increased HR (CO=HRxSV)

2. Increased contractility of heart muscle

3. Increased preload (volume before contraction)

Blood pools in the lower extremities due to what?

What is used to prevent this?

It is due to pull of gravity and high vein compliance

- muscular activity prevents the pooling

If fluid moves from the interstitium due to increased pressure, what presents if it is deposited faster than lymphatics drain it?

Decreased venous return has what effect on SV and CO?

What can the patient present with?

decreased SV and CO

fainting due to low output if no compensation happened when standing up

What are the steps of standing compensatory mechanisms?

1. carotid baroreceptors = sympathetic outflow

increase:
- HR
- Contractility
- TPR/SVR - increased preload

Increased:
- venous return
- BP

During exercise, what happens to the SV?

SV is increased at any level of exercise

- max HR does not change with conditioning

Coronary blood flow occurs during which phase of the cardiac cycle?

why?

diastole for both rest and exercise

heart muscle during contraction constricts the vessels between muscle (coronaries lay atop of the muscle)

Pulmonary vascular resistance and SVR/TPR during exercise have what kind of compensation?

they both decrease

SVR/TPR = large decrease, dilation of skeletal muscle vascular beds
- venous system does constrict to have an increased venous return

Mechanisms leading to cardiac dysfunction:

1. failure of the pump
2. Obstruction of flow
3. Regurgitant flow
4. Disorder of cardiac conduction (arrhythmia)
5. shunted flow (ASD, VSD..)
6. disruption of continuity of circulatory system (rupture)

Heart failure occurs when

There is an inability of cardiac output to meet the metabolic requirements of tissues or organs

Common end stage of chronic heart disease:

chronic work overload (HTN, valve disease)

ischemic heart disease (post-MI)

CO low

systolic/diastolic dysfunction

What is meant by systolic dysfunction?

insufficient ejection fraction

decreased forward flow

- MI, dilated cardiomyopathy, valve disease

What is meant by diastolic dysfunction?

stiff ventricle, cannot relax during diastole
myocardial hypertrophy (HTN, DM, obesity, bilateral renal artery stenosis)

restrictive cardiomyopathy (fibrosis/deposition)

Diastolic dysfunction leads to :

Systolic dysfunction

- common in women over 65

When does high output cardiac failure occur?

- 2 most common examples

occurs when normal cardiac output cannot meet increased oxygen demands

1. increased metabolism - hyperthyroidism
= hypertrophy/cardiomyopathy

2. decreased systemic vascular resistance direct increased flow into venous circulation

Ex: thiamine deficiency

Frequent causes of high output cardiac failure:

1. wet beri beri = thiamine deficiency
(circulatory = wet; neural = dry)

2. Graves disease (high metabolic rate)- Hyperthyroidism

3. Pregnancy (twin, triplet, etc)

4. Severe anemia

Causes of left sided heart failure (low output)

ischemic heart disease (IHD)

Systemic HTN

Aortic and mitral valve disease

Causes of right sided heart failure (low output)

Left sided heart failure

Pulmonary HTN

"Cor pulmonale"

Cardiac hypertrophy
- what it is
- 2 causes

sustained increase in mechanical work from pressure, volume overload or trophic (hormonal)

1. Pressure overload (HTN) - sarcomeres in parallel = concentric increased in wall thickness

2. Volume overload - sarcomeres increased in series = dilation of wall

Concentric hypertrophy

increase in ventricle wall thickness

Eccentric hypertrophy

increase in ventricle chamber size (dilated ventricle)

What is the best measure of hypertrophy in dilated heart?

weight, 2-4x normal

What happens to the vasculature of a hypertrophied heart?

there is NO increase in capillary number

- increased demands are NOT met with increased vasculature to supply the thicker muscle

Hypertrophy from regular strenuous exercise would be classified as what type of hypertrophy?

physiologic hypertrophy

Hypertensive heart disease
- left sided vs right sided

left sided = systemic HHD

right sided = Cor pulmonale (from pulmonary hypertension)

Systemic hypertensive heart disease needs:

1. left ventricular hypertrophy (concentric)

2. Hx of pathologic evidence of HTN in other organs (kidney)

Clinical presentation of a patient with systemic hypertensive heart disease:

- may be asymptomatic with only EKG changes of LVH

- new onset a-fib from left atrial enlargement

Outcomes resulting from systemic hypertensive heart disease:

HTN-> atherosclerosis and increased hear muscle o2 demand
- Ischemic heart disease

Normal vs hypertrophic myocardium
- histo

hypertrophied:
- enlarged myocytes
- enlarged "boxcar" nuclei

What does "right dominant heart" mean?

Right coronary supplying 1/3 of the interventricular septum
~80%

is the delay of the AV node
- allows for filling of the ventricles

ventricular depolarization

Clinical features of Left heat failure:

pulmonary congestion/edema

- orthopnea
- frothy sputum
- wheezing
- basal rales
- S3

Left sided heart failure is related to:

- passive congestion of lung
- stasis/reduced flow through left
-inadequate tissue perfusion
organ dysfunction

Left sided heart failure can have what kind of effects in the heart, lung, and brain?

heart:
- LV hypertrophy/dilation
- LA dilation and valve dysfunction

Lung:
- congestion
- edema

Brain:
- hypoxia

Hypertrophy impairs __ filling, leading to ___ with increased risk of _______

diastolic

leading to atrial enlargement with an increased risk of atrial fibrillation

Which vessel perfuses the anterior wall of the left ventricle?

Left anterior descending (LAD)

40-50% of infarcts

Clinical features of right sided heart failure:

all related to increased congestion of venous circulation
- dependent edema
- ascites
- jugular vein distension

enlarged tender liver = nutmeg liver
- could get enlarged spleen/kidney

Right sided heart failure can cause what presentations in the heart, brain, and passive congestion in which organs?

heart:
- RV hypertrophy/dilation
- RA dilation

passive congestion:
- liver
- kidney
- spleen

Brain:
- hypoxia (poor volume output)

right ventricular hypertrophy and heart failure due to primary pulmonary hypertension

NOT left sided heart disease

Acute cor pulmonale

Dilation of right heart from pulmonary thromboembolism that can lead to sudden death

chronic cor pulmonale

right ventricular hypertrophy secondary to prolonged pressure overload seen in association with pulmonary hypertension disorders

RV hypertrophy and Cor pulmonale can occur from which disease?

- what is the effect on alveolar capillaries?

Can occur from Emphysema/COPD/Smoking

alveolar capillary stretching/flattening = increased pulmonary pressure

Cor pulmonale is a ___ sided heart failure caused by a primary __ problem.

right sided; primary lung problem

NOT caused by LHF

What is the dominant cause of ischemic heart disease?

insufficient coronary perfusion relative to myocardial demand

What is present in 90% of the cases in patients who have Ischemic heart disease/CAD?

Atherosclerosis

Clinical syndromes of patients with Ischemic heart disease/ CAD?

- which are referred to as acute coronary syndrome?

1. angina pectoris "chest pain"

2. MI - frank myocyte necrosis

3. sudden cardiac death

4. Chronic IHD

angina pectoris (chest pain)
- types

not severe enough of an occlusion to cause infarct
1. stable
2. unstable (crescendo, pre-infarct)
3. Printzmetal (transient ST elevation)

Which subsets of angina pectoris may have ST depression?

stable and unstable

When is death estimated to occur in sudden cardiac death (SCD)?

within 1 hour of symptom onset

Stable/Typical angina
- duration + Sx
- exacerbation
- alleviation
- EKG

15 sec- 15 minutes
- deep poorly localized pressure, squeezing, burning with radiation to left arm or jaw

- fixed atheromatous narrowing - generally not acute plaque disruption

- exacerbation: physical activity, emotional excitement, stress

- alleviation: vasodilators

EKG:
- may have ST segment depression with exercise or may be normal

Printzmetal (variant) angina
- demographic
- cause
- Sx
EKG
- Rx

younger women, smokers, cocaine, alcohol

Cause:
- coronary artery spasm- unrelated to activity (usually sleeping)

Sx:
- pain at rest, lightheaded, excessive sweating and cannot be induced with stress test (exercise tolerant)

EKG:
transient ST segment elevation- mimics acute MI
- No Q wave or T wave inversion (as in MI)

Rx: vasodilators

Unstable (preinfarction, crescendo) angina
- Sx
- pathology
- caused by
- warning sign?
- EKG /serology

progressively decreased activity levels = eventually get to pain at rest
- progressive increase in frequency, duration and severity of pain (>20 minutes)

Patho:
- 90% obstruction of cross sectional area = inadequate perfusion at rest

Cause: disruption of plaque with superimposed thrombosis, embolus, and/or vasospasm

Forerunner of MI = imminent

EKG: +/- ST depression/T inversion
NO increase of cardiac anzymes

What is a MI?

- strong correlation?

death of cardiac muscle due to severe ischemia

strongly correlated to atherosclerosis

What is protective against myocardial infarction in women?

estrogen until menopause

Sequence of pathogenesis of MI:

1. plaque changes
2. sub-endothelial collagen exposed
3. vasospasm
4. coagulation cascade = thrombus occlusion of vessel

Myocardial response to ischemia

reduced production of ATP = lactic acid

contractility ceases within a minute of severe ischemia = myocyte death takes long (20-30 minutes)

>20-30 minutes = irreversible damage/necrosis of myocytes

What can confirm MI?

myocardial. proteins

Where is ischemia most pronounced first? why?

subendocardium

more vulnerable (end of line)

Cardiac enzymes present during a myocardial infarction?

1. Troponin T or I (cTnT or cTnI)
- elevated for 6-10 days
**stays elevated after CK-MB returns to normal - not new event

has the most specificity for cardiac muscle,

elevated for 2-3 days

Clinical presentation of MI:

constricting, squeezing, pressure, choking,

Sometimes radiates to left arm and jaw

asymptomatic (10-25%) elderly and diabetics
- rapid, weak pulse, perfuse sweating

- dyspnea

Transmural Myocardial infarction:

complete blockage of epicardial/cardiac vessel

EKG:
Q wave exaggerated (more down) = myocardial death/cell necrosis

- remains on EKG, not time specific

ST elevation (STEMI)

subendocardial infarction

area least perfused - most vulnerable

1/3 of wall thickness = not full thickness

resolves before full thickness necrosis can occur

EKG for subendocardial myocardial infarction:

absence of Q wave = non-Q wave MI

ST segment depression (NSTEMI)

Severe reduction in blood pressure (ie:shock) superimposed on non-critical coronary stenosis, will result in?

circumferential subendocardial infarct - not single artery distribution

global hypoperfusion = global subendocardial effect

Change timeline in MI:
0-4 hours
4-24 hours

1-3 days
3-7 days
7-10 days

0-4 hours: NO CHANGES

4-24 hours: in order of appearance
1. wavy fibers (3-12 with edema)
2. contraction band necrosis
3. early neutrophils (12-24 hours) - coagulation necrosis

1-3 days:
- dense neutrophilic infiltrate (coagulation necrosis)

3-7 days:
- macrophages and dead cells

7-10 days:
- macrophages and granulation tissue

Acute MI of posterolateral LV

- what enzyme is preserved is some areas with nonexistent (leaked out) in other areas?

Lactate dehydrogenase preserved in non-infarcted myocardium

no LDH = white

What is seen in the myocardium 1 day post-infarct?

wavy fibers with edema + fluid in between

4-12 hours

early coagulative necrosis (6-12 hours)

What does contraction band necrosis look like on histology?

zebra-like lines

loss of nuclei

seen within 4-24 hours

What does a 3 day old infarct look like on histology?

dense neutrophilic infiltrate

- most prominent 1-3 days

What does a 3-4 day old infarct look like on histology?

- cells presents?

3-10 days macrophages remove necrotic myocytes

What does granulation tissue look like post-infarct?
- when is it most prominent?

Loose collagen (blue fibers)
- trichrome stain

Abundant capillaries

Most prominent at 1-2 weeks

Ischemic heart disease/coronary artery disease
Clinical syndromes:

1. angina pectoris

2. myocardial infection - ischemia causes frank myocyte necrosis

3. chronic IHD with heart failure/"ischemic cardiomyopathy"

4. sudden cardiac death (SCD) - unexpected death from cardiac causes

When does the myocardium stop contracting once ATP is depleted?

When does myocyte death begin when ATP is depleted?

After 2-3 hours of ATP depletion, what results in the myocardium?

myocyte death has occurred
- reperfusion here
- histology begins with the wavy fibers

During MI treatment, the goal is prompt ____.

prompt reperfusion
"Time is myocardium"

1/2 of the deaths from a MI occurs in ___.

first hour (Arryhthmias)

- many don't get to the hospital

The first 3-4 hours of MI are critical, and is diagnosed by:

clinical, lab myocardial proteins, and EKG

Contractile dysfunction from MI
- results
- prognosis

LV failure (hypotension, pulmonary congestion = pulmonary edema)

Cardiogenic shock - 70% mortality

Arryhthmia secondary to MI
- results:
- prognosis

arrhythmia is myocardial instability/conduction disturbances

most common cause of death within first few hours of MI

Myocardial rupture secondary to MI:

due to transmural necrosis

ventricle free wall - most common (anterolateral) 2-8 days after MI - wall is weakest and vulnerable

causes hemoperricardium and cardiac tamponade

Pericarditis secondary to MI:
- results (syndromes)
- timeline of occurrence

2-3 weeks to months post MI

Dressler syndrome
- patient has friction rub on PE
fibrinous pericarditis (transmural)

Ventricular aneurysm
- results possible

thromboembolism

scar tissue bulges during systole = thrombus formation, arrhythmia, heart failure

Mural thrombus secondary to MI:
- results
- how is a hx of MI related to this?

abnormal contractility = stasis

Hx of MI= can cause thrombus to embolus to brain or other organs/limbs

Papillary muscle rupture
- results
- patient presentation

papillary muscle rupture = acute mitral regurgitation

new onset murmur post MI = papillary muscle problem ! ! ! !

Progressive late heart failure secondary to MI:
- results

chronic ischemic heart disease

MI prognosis
- factors to take into account
- mortality

- compensatory mechanism

factors: infarct size, location and fraction of wall involved (transmural?)

overall 30% mortality first year and 3-4% each additional year

Compensation:
compensatory hypertrophy and dilation of non-infarcted myocytes

Ventricular remodeling is a result of:

- what are risks due to this compensation?

myocardial ischemia

- hemodynamically helpful but can increase o2 demands = increased ischemia = decreased function

Major causes of death with MI complications:

1. cardiac arrhythmia - major cause in first few hours

2. cardiogenic shock

3. CHF
4. thromboembolization

Sudden cardiac death
- caused by
- prognosis

death usually within one hour of developing symptoms

usually from lethal arrhythmia (v.fib)

How does sudden cardiac death happen?

1. 80% coronary artery disease

2. Cardiomyopathies - most common non-ischemic cause of sudden cardiac death
- dilated, alcoholic, idiopathic, fibrotic, or hypertrophic

3. genetic

[In reality] What is the most common cause of sudden cardiac death in patients that are younger than 35?

fatal arrhythmia in a structurally normal heart

[Boards]
What is the most common cause of sudden cardiac death in patients who are 14-24?

- demographic?

hypertrophic cardiomyopathy (HOCM)

- sudden unexplained death in young athletes

What is chronic ischemic heart disease clinically called?

ischemic cardiomyopathy

progressive CHF from ischemic damage and/or inadequate compensation

How does chronic ischemic heart disease show up physically on the myocardium?

discreet scars of healed infarcts

myocardial hypertrophy and ventricle dilation

endocardium is patchy fibrosis due to abnormal wall shear forces from turbulent flow

Anterior Myocardial Rupture (pic)

Mural thrombus (pic)

Rupture with hemoperricardium (pic)

Left ventricular aneurysm
- what happens to the ventricle wall, and why?

bulging of the ventricular wall due to weakness from MI

What are some associated valvular disease?

1. aortic stenosis
2. mitral stenosis
3. mitral regurgitation (mitral valve prolapse)

What valvular problems are associated with rheumatic heart disease?

aortic stenosis, mitral stenosis

What are all valve defects at risk of developing?

infectious endocarditis

What is the etiology of aortic stenosis?

congenital valve defect (bicuspid)

acquired
- wear and tear degenerative disease in elderly (calcific stenosis)
- scarring of rheumatic disease

What are the effects of aortic stenosis?

1. increased afterload
- syncope = poor blood flow to the brain

2. LV hypertrophy - working against increased pressure
- incomplete left ventricular filling

3. pulmonary congestion (backup into lung vasculature)
4. RV strain (pump against congestion)

What are symptoms of aortic stenosis?
- auscultation?

Classic triad = dyspnea, syncope, angina

Auscultation:
- harsh systolic ejection murmur (R 2nd intercostal) radiating to the carotids

What is the cause of calcific aortic stenosis?
- demographic
- clinical presentation

wear and tear - dystrophic calcification

demographic: 2% of population - seen in elderly

Presentation:
- syncope
- angina on exertion, dyspnea or CHF

If there is an elderly patient with syncopal episodes, what is the most likely diagnosis?

aortic stenosis

Calcific aortic stenosis is associated with ____.

aging

- congenital bicuspid valve (50%)
- rheumatic heart disease

Hypertrophic obstructive cardiomyopathy (HOCM)
Idiopathic hypertrophic subaortic stenosis (IHSS)
- inheritance
- mutation
- pathology

AD
Beta myosin heavy chain gene mutation

hyper contractile heart muscle with poorly compliant left ventricle

= abnormal diastolic filling, systolic function is ok

Myocardial hypertrophy
- presentation
- where is the obstruction?

usually asymmetric septal hypertrophy (free wall less) without dilation

left ventricular outflow obstruction
- subaortic thickening

LV thick walled and heavy associated with HOCM and IHSS:
- causes

1. massive myocyte hypertrophy
2. myofiber bundle disarray '
3. interstitial fibrosis

What does hypertrophic cardiomyopathy look on histology?

myocyte hypertrophy and myofiber bundle disarray

- myocytes not arranged properly

Restrictive cardiomyopathy is:
- causes

decrease in ventricular compliance, impaired ventricular filling during diastole

caused by:
- infiltrating diseases, radiation fibrosis or scarring

Causes of restrictive cardiomyopathy

1. amyloidosis
2. sarcoidosis
3. endocardial fibroelastosis - thickening of LV during first 2 years of life
- looks like endocardium covered in thick white cheese

Amyloidosis
- histo

deposition of proteins in organs and tissues

Congo Red + polarization = Apple green birefringence

Endocardial fibroelastosis is commonly seen in which patients?

fibrosis of endocardium in infants and young children

What is the most common cause of myocarditis?

viral
- Coxsackie A and B

- can lead to dilated cardiomyopathy

If myocarditis is caused by a parasitic infection, what is the disease at risk?

Trypanomas cruzi (Chagas disease)
- parasites of myofibers

- can get myocarditis that leads to cardiac insufficiency in 10-20 years

If myocarditis is caused by hypersensitivity, what type of inflammation presents?

eosinophilic inflammation

Giant cell myocarditis

multi-nucleate giant cells, end stage myocarditis = poor prognosis

Cardiotoxic drugs causing myocarditis:

chemotherapeutic agents

Myocarditis can be _____, and cause __ or evolve into _______

asymptomatic; cause acute heart failure or evolve into dilated cardiomyopathy

Viral Myocarditis
-HISTO

lymphocytic infiltrates between myocytes

no neutrophils

"Lymphocytes between myoocyte bundles" = VIRAL

Non-inflammatory pericarditis

1. hydropericardium
2. hemoperricardium

Hydropericardium

serious transudate in pericardial space
- from any condition causing edema (CHF, nephrotic syndrome)

Hemopericardium

accumulation of blood in the pericardial sac

- traumatic perforation of heart, aortic dissection, post-MI

Acute pericarditis is usually caused by:
- common type

usually idiopathic or viral cause

1. serous pericarditis - viral

Acute pericarditis symptoms
- clinical
- auscultation
- relief

sharp piercing pain in center or left chest = worse with inspiration or cough

Pericardial friction rub - 85% lower left sternal border (grating, scratching)

SOB with reclining

Relief:
- relief sitting up and leaning forward

Acute serous pericarditis
- causes
- fluid characteristics

viral, SLE, rheumatic fever

serous = clear, straw colored, protein rich exudate

Acute pericarditis
- suppurative type characteristics
- causes

bacterial infection
- cloudy inflammatory exudate or pus

- Staph, Strep, Pneumococcus (pneumonia), some fungal infections

scarring = constrictive pericarditis

Sanguinous/Hemorrhagic Pericarditis
- Causes
- associated diseases

blood inflammatory exudate

most common= tumor infiltration

TB

Fibrinous pericarditis
- associations
- fluid

fibrin rich exudate

- uremia, myocardial infarction, rheumatic fever

Caseous pericarditis
- causes

direct extension of TB in tracheobronchial lymph nodes

Primary pericarditis
- prevalence / origin

rare and almost always viral origin

Secondary pericarditis
- most frequent precursors "RUMS"

pericarditis secondary to another disease/disorder

Radiation (chest) or Rheumatic fever
Uremia
Myocardial infarction
Systemic lupus erythematous

composed of fibrinous/serous exudate

What are types of chronic pericarditis?

1. adhesive mediastinopericarditis

2. constrictive pericarditis

Adhesive mediastinopericarditis
- predisposing factors
- what happens to the pericardial sac?
- results

may follow infectious pericarditis, previous cardiac surgery, or irradiation of mediastinum

sac is obliterated and pericardium adheres to adjacent structure = functional stressors

cardiac hypertrophy and dilation

Constrictive pericarditis
- sac characteristics
- results

heart encased in a dense, fibrous, fibrocalcific scar that limits diastolic expansion and cardiac output

mimics restrictive cardiomyopathy

What are some primary benign tumors of the heart?

1. Myxoma - most common
2. Fibroma - fibrous
3. Lipoma - tumor of fat
4. Rhabdomyomas - most common primary tumor pediatric heart

What is the most common malignant primary tumor of the heart?

Myxoma
- size
- location
- histo
- complications

most common primary tumor of the heart - benign

1cm - 10cm in size

location:
- commonly in the left atrium (fossa ovalis)
Histo:
- mucopolysaccharide matrix with focal vessels and gland structures

Complications:
- can embolize or cause fever and malaise (IL-6)

Rhabdomyoma
- demographic
- associated disease
- prognosis

most frequent primary tumor of the heart in infants and children

associated with tuberous sclerosis - TSC1 or TSC2 tumor suppressor gene (50%)

often regress spontaneously (Hamartoma)

Spider cells seen microscopically

What type of tumors are more frequent than primary tumors?

malignant tumors

1. carcinoma of the breast
2. bronchogenic carcinoma
3. lymphomas
4. leukemias
5. melanomas

Carcinoid heart disease
- what is it
- commonly affected site

cardiac manifestations caused by bioactive compounds

GI carcinoid with hepatic metastasis

Right side of heart affected (lung capillary bed protects the left heart = intimal plaque-like thickening = subendocardial fibrosis of the right heart

Associated finding from carcinoid syndrome (Sx)
- clinical
- serum

- episodic cutaneous flushing
- diarrhea
- cramps

serum:
- elevated serum Serotonin (5HT) and urine metabolite (5-HIAA) - follow disease severity

Infective/Bacterial endocarditis
- Sx
Acute stage
- causative agent
- serum
- risks
- prognosis

SX: fever, Janeway lesions, Osler nodes

ACUTE: highly virulent and destructive
Staph Aureus
previously normal vales
death can occur within days to weeks

IV drug users (tricuspid, pulmonic)

Subacute endocarditis
- characteristic
- Sx
- causative agent

Subacute = less virulent, less destructive course

- previously damaged valves

- Streptococcus viridans (50-60%)

Non infective thrombotic (Marantic) endocarditis
- demographic
- clinical presentation
- serum levels

malnourished and cancer patients (especially adenocarcinoma)

STERILE clots on valve - not destructive

presents as new onset stroke in a cancer patient
Blood cultures are negative

What is cardiomyopathy?

Non-inflammatory disorders of the myocardium; not caused by HTN, Congenital heart disease, valve disease or CAD

What is the typical patient who would be presenting with cardiomyopathy?

younger age of the patient and progressive deterioration

Dilated cardiomyopathy
- likely causes
- associated mutations

usually unknown cause, but alcoholism, viral, and drugs can cause it

- can be associated with certain protein mutations

Restrictive cardiomyopathy
- results
- best example

infiltrative process within the myocardium = stiffening of the heart muscle - interfere with proper pumping/contraction

Best example = cardiac amyloidosis

Hypertrophic cardiomyopathy
- inheritance
- effects seen on the heart

AD inheritance (different protein mutations)

hypertrophy of all chamber walls especially the septum
disoriented, tangled, and hypertrophies myocardial fibrils

Types of pulmonary HTN:
- defining characteristic of each

1. Left heart failure type
- "pulmonary venous HTN" due to increased volume

2. Hypoxia induced
- constrict areas not being well ventilated to maintain V/Q ratio
- improve with O2

3. Remodeling type "pulmonary arterial hypertension"
- irreversible = deadly
- can be end result of #1 or #2 or anything that causes congestion/volume over time

Congenital Cardiac malformations with cyanosis:

5T's

Tetralogy of Fallot
Transposition of the great arteries
Truncus arteriosus
Total anomalous pulmonary venous return (connection)
Tricuspid atresia

What is the most common type of heart disease in children?
- causes/etiology

Congenital heart disease (CHD)

multifactorial factors; etiology only in 10% of cases
- sporadic genetic abnormalities are major known causes

What are some major congenital defect categories?

1. obstructive defects
2. shunt defects

Patent ductus arteriosus may be needed in congenital heart defects for _____

- what can be used for this?

survival

Prostaglandins delay closure
Indomethacin promotes closure

Right to Left shunt vs. Left to Right shunt:

Left to right = non-cyanotic

Right to left = cyanotic

Obstructive congenital heart disease

-Examples
- results on heart muscle

coarctation of the aorta, aortic valvular stenosis, and pulmonary valvular stenosis produce abnormal narrowing of chambers
-complete obstruction is called atresia

may cause low volume and low muscle mass

In obstructive congenital heart disease, when would hypoplasia occur vs. atrophy?

hypoplasia = occurs before birth
atrophy = develops postnatally

What is the most common congenital heart disease, with a left to right shunt?
- results on the heart
- results long term

***ventricular septal defect

chronic elevation of pulmonary pressures = pulmonary HTN
- medial hypertrophy and vasoconstriction on pulmonary vasculature

Can lead to long term permanent changes seen in systemic htn
- atherosclerotic lesions
- right ventricular hypertrophy

Right to left shunt congenital heart disease
- clinical presentation
- causes of ___ heart disease:

Right --> Left = cyanosis from early on
- creates hypoxemia and dusky blue skin/mucus membranes
- paradoxical embolism
- hypertrophic osteoarthropathy
- polycythemia = due to chronic low o2 levels

Causes of cyanotic heart disease (5T's)

Large left --> right shunt that increases ___ blood flow.. = __ HTN = __ RV pressure = ___ to ___ shunt

pulmonary

pulmonary
increased RV pressure
right to left shunt (SWITCH)

What is the syndrome that develops when a large left --> right shunt becomes a right --> left shunt over time?

- is there cyanosis?

Eisenmenger Syndrome
BAD

- cyanosis

What are causes of the left to right shunt?

How do the patients with a left to right shunt present?

- what is the cause of their presentation??

start out ok (pink) then eventually with time and increased pulmonary HTN they get blue
due to Pulmonary HTN ***

- have a murmur that is untreated --> fatigue, cyanosis

Ventricular septal defect (VSD)
1. membranous
2. muscular

- pathology of the shunts:
- presentation in childhood:

most common overall type of CHD
- if in pediatrics, there are likely other anomalies
- adults, it is likely isolated defect

1. Membranous VSD = usually single and large (90%_ = most common congenital heart disease

2. Muscular = small and multiple = can close spontaneously via proliferation of cardiac stem cells

starts as left-right shunt = increased pulmonary blood flow = RV hypertrophy

reversal of shunt = tardive cyanosis (Eisenmenger complex)

***presents with a holosystolic/pansystolic murmur

Atrial septal defect (ASD)
- presentation
- path

incomplete tissue formation
communication of blood between left and right atria

usually asymptomatic until adulthood

NOT same as patent foramen ovale since FO is not considered a congenital defect

What is the most common CHD discovered in adults?

- pathology of this
- heart sounds
- presentation

ASD **

Path:
Left - right shunt due to P gradient and RV compliance

Right side atrial overload = increased pulmonary blood flow

murmur from excess pulmonary valve flow or flow through ASD

fixed S2 split of heart sounds (delayed closure of pulmonic valve) = delayed closure due to increased RV volume

generally well tolerated - often asymptomatic before age 30

What are some different ASD classifications?

1. Septum secundum deficient growth = Secundum ASD
most common type
- usually not associated with other abnormalities

2. Ostium primum = seen in Down syndrome - due to endocardial cushion defects

3. Sinus venosum = near entrance of SVC

Patent ductus arteriosus
- intrauterine function
- newborn function

intrauterine = blood flow can bypass unoxygenated lungs

newborn = closes in 1-2 days, complete obliteration = ligamentum arteriosum

- closes due to oxygenation, reduced prostaglandin E2 (natural), lower pulmonary pressure (first breath)

Result of delayed closure of the patent ductus arteriosus

hypoxemia
acidosis
prematurity
congenital defects - VSD (increased pulmonary P)
congenital rubella
complete transposition of the great vessels
tetralogy of fallot

Clinical presentation of patent ductus arteriosus:
- shunt type
- cyanosis?
- heart sounds?

machinery murmur throughout systole and diastole

initially left -- right shunt = no cyanosis

- large shunts = increased pulmonary pressure = HTN = reversal of shunt

Congenital malformation, ____ _____ _____, may be life saving.

- which drugs are associated with this process?

Patent ductus arteriosus may be life saving

Medication:
1. Prostaglandin = delays closure
2. Indomethacin = promotes closure

Tetralogy of Fallot

key characteristics that classify TOF

What determines the prognosis?

most common form of cyanotic CHD = NOT CH2 signaling pathway

Four components:
1. Subpulmonic (infundibular) stenosis (most common) or valvular stenosis
2. Dextraposition of the aorta
3. VSD
4. RV hypertrophy (secondary)

** degree of pulmonic/ subpulmonic stenosis: determines prognosis ***

What is the problem and solution to Tetralogy of Fallot:

Problem:
- restriction of blood flow into the pulmonary artery due to stenosis = minimal amount of blood getting oxygenated

Solution:
- if stenosis is severe they must have PDA (patent ductus arteriosus) to get blood to pulmonary artery to get blood oxygenated

VSD allows blood entering right heart to get to the left heart (otherwise minimal return from pulmonary vein into LA)

What are the clinical findings in a patient with Tetralogy of Fallot?

Complications?

****boot-shape heart on x-ray - from right ventricular hypertrophy

Pulmonary hypotension
- can have complete atresia of pulmonary valve/arteries
= blood flow through PDA and/or dilated bronchial arteries = survival

right sided aortic arch present in 25%

Complications:
- infective endocarditis
- cerebral abscess
- secondary polycythemia increasing likelihood of thrombosis
- clubbing of the fingers (cyanosis)

What are the outcomes of tetralogy of fallot?

depends on the extent of pulmonary obstruction

mild sub-pulmonary stenosis = right shunt (like VSD) = pink tetralogy

more severe RV outflow obstruction= right - left shunt = cyanosis

MOST = cyanotic soon after birth

What are tet spells?

cyanotic with crying, fever, hypotension --> squatting reverses the shunt

- subpulmonic stenosis protects from pressure overload = no right sided heart failure

pressure relieved from shunt to LV and aorta

What is the most common form of transposition of the great vessels?

problem associated with TGA

complete
1. aorta - arises from the RV
2. pulmonary artery - arises from the LV

problem:
- RA/ventricle receives venous blood and pumps venous blood into aorta and LA/ventricle receives oxygenated blood and pumps it back into the lungs
2 separate system (systemic + pulmonic) = not compatible with life!!

Solution to transposition of the great vessels.

survival requires a PDA or septal defect (to have mixed systems for o2 to get to tissues)

Heart characteristics of patients with transposition of the great vessels:
- associated abnormalities
- physical properties of the heart
- shunt?

35% VSD
65% have patent forman ovale or ductus arteriosis

need shunt to survive (keep open with prostaglandins)

RV hypertrophy prominent because supplies systemic circulation

Heart shaped like an egg

Truncus arteriosus is the failure to separate the truncus arteriosus into the ___ and ______

- blood received into ___
- clinical presentation
- blood flow effect?

aorta and pulmonary artery

blood received into a single great artery (like an elephant trunk)

presence of early cyanosis - mixed blood anyways

increased pulmonary blood flow

Tricuspid atresia is the complete ___ of the tricuspid valve orifice.

- Associated with:
- Problem:
- Solution:

complete occlusion

associated with:
- hypoplastic RV
- atrial septal defect
- VSD

problem: no tricuspid valve = no blood to RV or pulmonary system = no oxygenation of blood

solution: Must have ASD or VSD to allow blood to circulate through other chambers into RV

In which anomaly do all four pulmonary veins connect to the SVC?

total anomalous pulmonary venous return

- dumping into the venous side and not returning to the LA

Preductal coarctation
- location
- clinical Sx
- disease associated

proximal to PDA

PDA supplies deoxy blood to lower extremities because of lower aortic pressure after coarctation

Clinical:
- early cyanosis in lower extremities only
- HTN in upper extremities
- LV hypertrophy
- Difference in upper/lower BP - weak distal pulse

Associated with Turner syndrome

Postductal coarctation
- Clinical manifestations

Clinical:
- HTN involving upper extremities
- diminished or absent femoral pulses, cold lower extremities
- LV hypertrophy
- difference in upper and lower BP
- notching ribs on xray

What is the most common CHD overall?

Membranous VSD

- then ASD, PDA

What is the most common cyanotic CHD, while the patient is generally not cyanotic at birth?

Tetralogy of Fallot

What is the most common CHD with cyanosis immediately at birth?

Transposition of the great vessels

(PDA needs to remain open)

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