CNS sequelae of hypertension

Charcot-Bouchard aneurysms are microaneurysms that are less than 1 mm in diameter. They occur in the small penetrating arterioles that perfuse the basal ganglia, pons and subcortical white matter. These aneurysms occur due to long-standing hypertension and are prone to rupture. Hemorrhagic stroke would be evident on the intial CT scan as a focus of intraparenchymal hyperdensity.

Lacunar infarcts are small ischemic infarcts ( less than 15 mm in diameter), usually involving the basal ganglia, pons, internal capsule, or deep white matter of the brain. Lacunar infarcts occur most often due to hypertensive arteriolosclerosis of small, penetrating arterioles.

Neonatal complications of diabetes during pregnancy

• Premature delivery
• Fetal macrosomia
• Neural tube defects (e.g Caudal regression syndrome)
• Hypoglycemia
• Hypocalcemia
• Polycythemia
• Respiratory distress
• Transient hypertrophic cardiomyopathy.

Gram positive Cocci Classification

Sexual appearance of fetus at (second to third month) (third to fourth) and (at time of birth) of pregnancy

Sexual appearance of fetus at (second to third month) (third to fourth) and (at time of birth)of pregnancy.

Homocystinuria

Homocystinuria is caused by cystathionine synthetase deficiency. Affected individuals manifest with skeletal abnormalities resembling those of Marfan syndrome. In addition, they are also at high risk of developing thromboembolism. About 50% of affected patients respond to high doses of vitamin B6 (pyridoxine).

Homocystinuria is the most common inborn error of methionine metabolism and is caused by cystathionine synthetase deficiency. Thromboembolic episodes involving both large and small vessels, especially those of the brain, are classically associated with this condition and may occur at any age. Other clinical manifestations resemble those of Marfan syndrome. These include ectopia lentis, elongated limbs, arachnodactyly, and scoliosis.

Glycogen storage diseases

Polycistronic mRNA (Bacterial lac operon)

Bacterial mRNA can be polycistronic, meaning that one mRNA codes for several proteins. An example of polycistronic mRNA is the bacterial lac operon, which codes for the proteins necessary for lactose metabolism by E. coil; the transcription and translation of these bacterial proteins is regulated by a single promoter, operator, and set of regulatory elements. 

Multiple origins of replication (DNA replication)

The process of DNA replication is similar in eukaryotes and prokaryotes. The key steps involved in DNA replication are:
1. Unwinding of double stranded DNA (dsDNA) by helicase to produce single stranded DNA (ssDNA)
2. Formation of a replication fork
3. Formation of an RNA primer by the action of the enzyme primase
4. Synthesis and concurrent proofreading of daughter DNA strands by DNA polymerases
5. Ligation of Okazaki fragments on lagging strands by ligase and removal and replacement of RNA primers with DNA by DNA polymerase I
6. Reconstitution of chromatin and ligation of daughter strands.

In E. coil, a prokaryote, the three major types of DNA polymerase are DNA polymerase I, II and III. In eukaryotes there are five major DNA polymerases: alpha, beta, gamma, delta and epsilon. Though the eukaryotic genome is much larger and more complex than the prokaryotic genome, interestingly the size of the eukaryotic genome is not the source of its complexity. Its complexity results from the presence of a large number of non-coding DNA regions between coding regions. Within genes there are introns (Non-coding regions - Think “IN” between) separating exons (Coding regions - Think “EX” pressed). Prokaryotes rarely have introns within their genes.
In contrast to prokaryotes which typically have a single origin of replication eukaryotes have multiple origins of replication? With multiple origins of replication, the genome can be copied much more quickly because multiple regions are being replicated at once. 

Bilirubin metabolism

Prostate Anatomy

Location and Description

• The prostate is a fibromuscular glandular organ that surrounds the prostatic urethra . It is about 1.25 in. (3 cm) long and lies between the neck of the bladder above and the urogenital diaphragm below.
• The prostate is surrounded by a fibrous capsule. The prostate has a base, which lies  against the bladder neck above, and an apex, which lies against the urogenital diaphragm below. The two ejaculatory ducts pierce the upper part of the posterior surface of the prostate to open into the prostatic urethra at the lateral margins of the prostatic utricle.

Relations

• Superiorly: The base of the prostate is continuous with the neck of the bladder, the smooth muscle passing without interruption from one organ to the other. The urethra enters the center of the base of the prostate.
• Inferiorly: The apex of the prostate lies on the upper surface of the urogenital diaphragm. The urethra leaves the prostate just above the apex on the anterior surface.
• Anteriorly: The prostate is related to the symphysis pubis, separated from it by the extraperitoneal fat in the retropubic space (cave of Retzius). The prostate is connected to the posterior aspect of the pubic bones by the fascial puboprostatic ligaments.

• Posteriorly: The prostate is closely related to the anterior surface of the rectal ampulla and is  separated from it by the rectovesical septum (fascia of Denonvilliers). This septum is formed in fetal life by the fusion of the walls of the lower end of the rectovesical pouch of peritoneum, which originally extended down to the perineal body.
• Laterally: The prostate is embraced by the anterior fibers of the levator ani as they run posteriorly from the pubis.

Structure of the Prostate

• The numerous glands of the prostate are embedded in a mixture of smooth muscle and connective tissue, and their ducts open into the prostatic urethra.
• The prostate is incompletely divided into five lobes. 
• The anterior lobe lies in front of the urethra and is devoid of glandular tissue. 
• The median, or middle, lobe is the wedge of gland situated between the urethra and the ejaculatory ducts. Its upper surface is related to the trigone of the bladder; it is rich in glands. 
• The posterior lobe is situated behind the urethra and below the ejaculatory ducts and also contains glandular tissue. 
• The right and left lateral lobes lie on either side of the urethra and are separated from one another by a shallow vertical groove on the posterior surface of the prostate. The lateral lobes contain many glands.

Function of the Prostate

• The prostate produces a thin, milky fluid containing citric acid and acid phosphatase that is added to the seminal fluid at the time of ejaculation. 
• The smooth muscle, which surrounds the glands, squeezes the secretion into the prostatic urethra. 

Blood Supply

Arteries

• Branches of the inferior vesical and middle rectal arteries.

Veins

• The veins form the prostatic venous plexus, which lies outside the capsule of the prostate. The prostatic plexus receives the deep dorsal vein of the penis and numerous vesical veins and drains into the internal iliac veins.

Lymph Drainage

• Internal iliac nodes.

Nerve Supply

• Inferior hypogastric plexuses. The sympathetic nerves stimulate the smooth muscle of the prostate during ejaculation.

Benign Prostatic Hyperplasia

It is a benign enlargement of prostate which occurs after about 50 years (usually between 60-70 years)
Theories
It is involuntary hyperplasia due to disturbance of the ratio and quantity of circulating androgens and estrogens.
BPH is a benign neoplasm, also called as fibromyoadenoma.

Pathology

• BPH usually involves median and lateral lobes or one of them.
• It involves adenomatous zone of prostate, i.e. submucosal glands.
• Median lobe enlarges into the bladder.
• Lateral lobes narrow the urethra causing obstruction.
• Urethra gets elongated and narrowed.
• Bladder initially takes the pressure burden causing trabeculations, sacculations and later diverticula formation.
• Enlarged prostate compresses the prostatic venous plexus causing congestion, called as vesical piles leading to haematuria.
• Incrimination of BPH as the source of haematuria before excluding other causes is termed as “Decoy prostate”
• Kidney and ureter
• Back pressure causes hydroureter and hydronephrosis.
• Secondary ascending infection can cause acute or chronic pyelonephritis.
• Often severe obstruction can lead to obstructive uropathy with renal failure.
• BPH causes impotence.

Clinical Features

• Frequency occurs due to introversion of sensitive urethral mucosa into the bladder or due to cystitis and urethritis.
• Urgency
• Overflow and terminal driblling.
• Difficulty in micturation with weak stream and dribble.
• Pain in suprapubic region and in loin due to cystitis and hydronephrosis respectively.
• Acute retention of urine
• Retention with overflow
• Haematuria
• Renal failure
• Prostatism is a combination of symptoms like frequency both at day and night, poor stream, delay in starting and difficulty in micturation.
• Tenderness in suprapubic region, with palpable enlarged bladder due to chronic retention. Hydronephrotic kidney may be palpable.
• P/R examination shows enlarged prostate. It should be done when bladder is empty.
• Features of urinary infection like fever, chills, burning micturation.

Investigations

• Urine for microscopy and C/S
• Blood urea and serum creatinine
• USG abdomen- look for presence of residual urine
• Urodynamics
• Cystoscopy
• Acid phosphatase
• Prostate specific antigen (PSA)
• IVU
• Serum electrolytes

Management

• Patient with acute retention of urine requires urethral catheterization.
• If urethral catheterization fails, then suprapubic cystostomy is done.
• If patient presents with uraemia, then urethral catheterization is a must. That allows the kidney to function adequately and further obstructive damage is prevented.
• Serum electrolyte should be corrected properly in these patients.

Indications for surgery

• Prostatism (frequency, dysuria, urgency)
• Acute retention of urine.
• Chronic retention of urine with residual urine more than 200 ml.
• Complications like hydroureter, hydronephrosis, stone formation, recurrent infection, bladder changes.
• Haematuria

Surgeries

• Transurethral resection of prostate (TURP)

Using cystoscope with fluid like glycine irrigating continuously, enlarged prostate is identified and resected using a loop with a hand control. Resection is done using high frequency diathermy current.
After surgery, continuous bladder irrigation using NS is done using three way Foley’s catheter. Antibiotics should be given. Catheter is removed within 72 hours.

• Freyer’s suprapubic transvesical prostatectomy.Before TURP this was procedure of choice.

• Millin’s retropubic prostatectomy
• It is done without opening the bladder ( not commonly practiced)
• Young’s perineal prostatectomy through perineal approach.
• Laser treatment using holmium laser.
• High energy electromagnetic treatment.
• Placement of intraurethral stents at prostatic urethra.
• Placement of extraurethral stents which are inert.
• Transurethral balloon dilatation of the prostate.

Drugs used for BPH

1)Alpha 1 adrenergic blocking agents- which inhibit smooth muscle contraction of prostate. They reduce the bladder neck resistance so as to improve the urine flow

• Short acting drugs are prazocin and indoramin.
• Long acting drugs are terazocin and doxazosin.
• Selective alpha1A- adrenoceptor blocking agent: tamsulosin

2)5-alpha reductase inhibitor inhibits conversion of testosterone to dihydrotestosterone.

• It is effective in palpably enlarged prostate.
• Drug used is finasteride 5mg daily for 6-8 months.
• It is contraindicated in obstructive uropathy or carcinoma prostate.

Carcinoma of Prostate

 Epidemiology

•  Most common cancer in men
•  Second most common cause of cancer death in men
•  Incidence increases with age
•  Highest rate in African Americans

Gross

• ill-defined, firm, yellow mass
• Commonly arises in the posterior aspect of the peripheral zone

Micro

• Adenocarcinoma
• Gleason grading system

Spread

1.Local spread

• Tends to grow upwards to involve seminal vesicles, bladder neck, trigone, lower end of ureter.

2. Hematogenous

• Bone esp, pelvic bone and lower lumber vertebrae.( osteoblastic)
• Femoral head, rib cage and skull are other common sites.

3. Lymphatic

• Commonly goes to the obturator and pelvic lymph nodes

TNM Staging

1. T1a, T1b, T1c: incidentally found tumor.

T1a : tumor involving less than 5% of the resected specimen

T1b: Tm involving greater than 5% of the resected specimen

        T1c: impalpable tumor found following a raised PSA.

2. T2a: suspicious nodule on rectal examination confined within prostate capsule involving one lobe.

T2b: involves both lobes

3. T3: extends beyond the capsule

T3a: U/L or B/L extension

T3b: seminal vesicle extension

4. T4: tm which is fixed or invading adjacent structures other than seminal vesicles- rectum or pelvic side wall

Clinical Presentation

• Often clinically silent
• May present with lower back pain secondary to metastasis
• Advanced localized disease may present with urinary tract obstruction or UTIs

Investigations

• Digital rectal exam (induration)
• Serum PSA levels
• Transrectal U/S and biopsy
• Alkaline phosphatase elevated with metastasis
• Bone scan

Treatment

Local disease (T1 and T2):
 prostatectomy and/or external beam radiation

• Metastatic disease (T3 and T4): B/L Orchidectomy

• Estrogens or androgen receptor blockade (flutamide or leuprolide)
• Monitor with PSA levels