Cardio, Respi, Renal Block Flashcards
What are the different kinds of RNA polymerases seen in eukaryotes and prokaryotes?
Eukaryotes:
RNA polymerase I
-function restricted to nucleolus
-synthesize template for rRNA
NB: nucleolus is primary site of ribosomal subunit maturity and assembly. In malignant cells, large nucleus composed of prominent basophilic nucleoli seen
RNA polymerase II
-most regulated of all RNA polymerases by transcription factors
-synthesizes mRNA, snRNA, miRNA
RNA polymerase III
-synthesizes small RNA e.g. tRNA, 5s rRNA
Prokaryotes:
JUST RNA polymerase (multisubunit complex)
-makes all 3 kinds of RNA
Which drugs influence RNA polymerase functions?
A-amanitin in death cap mushrooms
- blocks RNA polymerase II
- causes severe hepatotoxicity
Rifampicin
-blocks RNA polymerase (multisubunit complex) in prokaryotes
Actinomycin-D (antitumor and antibacterial)
-blocks RNA polymerases in both prokaryotes and eukaryotes
How does silicosis present?
Hx
- occupational exposure e.g. miner, sandblaster
- chronic cough, hemoptysis, dyspnea, chest pain
- ***risk of TB and bronchogenic CA
PE
- fine crepitations at ULs (asbestos from roof affects base, coal and silica from earth affect roof)
- UL pulmonary nodules, hilar adenopathy with ‘eggshell’ calcifications
Ix
-histology: bifringent silica particles surrounded by fibrous tissue
What is the Pathophysiology of Silicosis?
Silica affects macrophage function (cell-mediated immunity)
- causes macrophage release of fibrogenic factors
- disrupts phagolysosomes, thereby releasing viable bacteria and lysosomal enzymes extracellularly
- these cause interstitial fibrosis (ILD) and predisposition to mycobacteria infections
What are the features of a Histoplasmosis infection?
Non-immunocompromised: asymptomatic or self-limiting pulmonary disease
Immunocompromised:
- systemic histoplasmosis (fever, weight loss, lymphadenopathy),
- ulcerative tongue lesions, hepatosplenolegaly,
- tuberculous features like pulmonary infiltrates, hilar adenopathy, cavitatory lesions in lung ULs if chronic, **macrophages filled with round yeasts on cytology (survives intracellularly)
Where is a thoracocentesis performed?
- Insertion of needle just above superior margin of rib to avoid subcostal neurovascular bundle.
- risk of injury to smaller collateral branches still persists
-Regions are between inferior margins of visceral and parietal pleura; At the midclavicular line: 6th - 8th rib At mid-axillary line: 8th - 10th rib At paravertebral line: 10th - 12th rib
- Needle inserted higher than landmarks –> penetrating lung injury.
- Needle inserted lower–> penetrating liver trauma (R), splenic/bowel trauma (L)
What are the cell types seen in respiratory epithelium?
CONDUCTING ZONE
Tracheobronchial tree:
- pseudostratified ciliated columnar epithelium
Bronchi and large bronchioles:
-goblet cells –> mucin producing
Terminal bronchioles:
-Club cells –> secretory, and regenerative source of ciliated cells in bronchioles
RESPIRATORY ZONE
respiratory bronchioles:
-ciliated cuboidal epithelium (cilia terminate here)
alveolar ducts and alveoli:
-simple squamous epithelium
largely Type I Pneumocytes –> thin for gas exch.
some Type II Pneumocytes –> regenerate alveolar lining during lung damage, precursors for Type I cells, surfactant production.
some alveolar macrophages–> derived from fetal monocytes,clear inhaled debris.
What is the pathophysiology and presentation of Fabry disease(a type of lysosomal storage disorder)?
Pathophysiology:
- X-linked recessive
- alpha-galactosidase A deficiency
- G3b accumulation in dorsal root, autonomic ganglia, cardiac myocytes, glomerular cells and vascular smooth muscles
In adolescence
- neuropathic pain and hypohydrosis exacerbated by exercise, stress, fatigue.
- Angiokeratomas and telangiectasias in clusters over groin, buttocks, umbilicus
In adulthood
- TIA,stroke
- cardiac disorders e.g. LVH
- Glomerular diseases(proteinuria), renal failure
Hepatomegaly presents in which lysosomal storage diseases?
Present
- Gaucher disease
- Niemann-Pick disease
- Hunter-Hurler syndrome
Absent
- Fabry disease
- Tay-sachs disease
- Krabbe disease
What is the pathogenesis and presentation of Neurofibromatoses type 1 and 2?
NF1:
- AD; mutations in NF1 gene on chr 17
- Neurocutaneous disorder, unlike NF2
- skin: cafe-au-lait spots, cutaneous neurofibromas, *neurofibrosarcoma (malignant nerve sheath tumor) can develop from neurofibromas
- eyes: optic gliomas, Lisch nodules (iris hamartomas)
- others: phaeochromocytoma
NF2:
- AD; mutations in NF2 gene on chr 22
- nil cutaneous features
- bilateral acoustic schwannomas, juvenile cataracts, meningiomas, ependymomas
What are the 2 types of asthma?
Allergic (extrinsic)
- suspect when non-allergic causes (see below) ruled out
- triggered by allergens like food (esp in children) and aeroallergens e.g. seasonal pollen, mold spores, animal dander, dust mites.
Non-allergic (intrinsic)
-triggered by exercise and/or stress, aspirin use, pulm infection, viral URIs, inhalation of irritants e.g. cig smoke
Patients present with paroxysmal breathlessness and wheezing when young
What are the pathological findings in asthma?
Sputum sample:
- eosinophils (granule containing cells)
- charcot-leyden crystals (double pointed needle-like crystals from eosinophil breakdown)
- curschmann spirals (shed epithelium forms whorled mucus plug)
What is the process of cardiac outflow tract formation?
-Truncus arteriosus rotates
-truncal and bulbar ridges appear and SPIRAL
-ridges fuse to form aorticopulmonary septum
This forms ascending aorta and pulmonary trunk
What is the pathogenesis and presentation of TGA?
- Conotruncal deformity
- Due to failure of aorticopulmonary septum to spiral (linear AP septum results)
- aorta lies anterior and connects to RV; pulmonary trunk lies posterior and connects to LV
- 2 parallel circulations
- not compatible with life unless L->R shunt e.g. PFO, VSD, PDA exists
Presentation
- normal infant at birth
- at age 1-3days, onset of cyanosis, tachypnea, tachycardia due to PDA closure
- machinery murmur +/- (PDA patency)
- raised lactate
- DEATH within first few months unless shunt created.
What is Persistent Truncus Arteriosus?
- Failure of conotruncal septation
- presentation: cyanosis and respiratory distress
- ECHO: single arterial trunk, overriding large VSD
Explain the immunologic process to combat Mycobacterium Tuberculosis.
- M.tuberculosis is an intracellular organism that survives in non-activated macrophages.
- combated by cell-mediated immune process
- CD4+ TH1 cells and macrophages play a key role
- CD4+ T cells activated by APCs
- resultant TH1 cells secrete IFN-gamma to activate macrophages
- macrophages secrete TNF-a to form granulomas: walling off immune reaction consisting of Langhans multinucleated giant cells, epithelioid cells fibroblasts and collagen.
- caseating granuloma allows macrophages in necrotic centre to kill off bacteria
What investigation is necessary to prevent a serious side-effect of Anti-TNF-a drugs?
test for latent TB = PPD
- TNF-a produced by macrophages maintains granulomas
- Anti-TNF-a can cause granuloma breakdown and disseminated disease.
How do kidneys form embryologically?
- urogenital ridge forms in intermediate mesoderm
- nephrogenic cord develops from UG ridge
- from nephrogenic cord, 3 sets of sequential nephric systems form:
1) pronephros- from cephalic nephrogenic cord, later regresses
2) mesonephros - from midportion of nephrogenic cord, interim kidney, permanent for males as wolffian duct (later ductus deferens and epididymis), regresses in females forming vestigial Gartner’s ducts
3) metanephros - true kidney, permanent.
- develops from ureteric bud
- ureteric bud sprouts from caudal portion of mesonephric duct
- ureteric bud penetrates sacral mesoderm, inducing formation of metanephric blastema (metanephric mesoderm)
- signals exchanged between bud and blastema help differentiate structures
- **Aberrant interaction between them produces congenital renal malformations
Which structures in adult kidneys develop from ureteric bud and metanephric blastema?
metanephric blastema:
- glomeruli
- Bowman’s space to DCT
Ureteric bud:
- Entire collecting system
- collecting tubules and ducts
- renal calyces
- renal pelvis
- ureters
What are the different categories of grafts ?
Autograft - from self e.g. Ross procedure
Isograft - from twin or clone e.g. Bone marrow, Kidney transplants
Allograft - from nonidentical individual of same species e.g. heart, liver, kidney
Xenograft - from different species e.g. bovine/porcine heart valve replacements
What are the different types of transplant rejection?
Categorized by acquity:
1) Hyperacute
- within mins to hours,
- preformed antibodies in recipient against donor antigens,
- widespread thrombosis of graft vessels seen with ischemia and fibrinoid necrosis
- Graft MUST be removed
2) Acute
- weeks to months
- exposure to donor antigens causes activation of humoral and cellular immunity
- vasculitis of graft vessels with dense lymphocytic infiltrate
- reversed/prevented with immunosuppresion
3) Chronic
- months to years
- refractory to immunosuppression and w/o precipitating factors e.g. active acute rejection, drug toxicity
- chronic low-grade cellular and humoral immune response to foreign antigens
- parenchymal fibrosis and later graft atrophy, arteriolosclerosis
What are the key findings in chronic renal allograft rejection?
- worsening HTN
- rising Cr
- proteinuria
- graft atrophy
How do the differing anatomies of L and R renal veins pose a problem?
R renal vein
- short course
- runs anterior to renal art. before draining into IVC
- R gonadal vein drains directly into IVC
L renal vein
- long course
- runs anterior to renal art., crosses aorta under SMA, then drains into IVC
- L gonadal vein drains into L renal vein, NOT IVC directly
- **Pressure in L renal vein generally higher due to compression between aorta and SMA (“nutcracker effect”) or L sided retroperitoneal/abdominal mass
- flank pain
- hematuria
- varicoceles: of pampiniform plexus of L testis (L gonadal vein insufficiency)
What is the management of a GBS +ve mother?
- prenatal screening at 35-37wks gestation for vaginal / rectal GBS colonization
- if +ve, intrapartum abx prophylaxis to prevent neonatal GBS sepsis, meningitis and pneumonia
- first line: penicillin
second line: ampicillin - abx given much earlier e.g. 30weeks serve to eliminate GBS temporarily
- postnatal Igs to affected infants has no true efficacy
- breastfeeding to continue as per normal;
benefits: mucosal immune protection by IgA, superior nutritional content, promote proper GI development
