Tag: Pathogenesis

Neovascular glaucoma-Pathogenesis


Neovascular glaucoma-Pathogenesis


  • Neovascular glaucoma (NVG) is a potentially devastating sequela of serious underlying ocular and/or systemic diseases.
  • The ocular diseases responsible for neovascularization of the iris (NVI) or neovascularization of the angle (NVA) that ultimately lead to NVG are almost always ischemic in nature
  • Under hypoxic conditions, diffusible angiogenic factors, including vascular endothelial growth factor, have been detected in the human and animal retina and vitreous, promoting new vessel growth.
  • Clinically, the three most common conditions responsible for NVG are diabetic retinopathy, central retinal vein occlusion and carotid artery obstructive disease.

Neovascularization:

→Highest O2 consumption in the eye → Retina

Hypoxia

VEGF

Neovascularization
Neovascular glaucoma-Pathogenesis:
Neovascularization

Retina

Vitreous

Iris (Rubeosis Iridis) → Neovascular Iris (NVI)

Neovascular glaucoma

→ Zipper – like closure

→ Secondary angle closure glaucoma

Venous Ulcers

Venous ulcers

Q. 1 Complications of obesity is/are:

1. Venous ulcer
2. Pulmonary embolism
3. Pickwickian syndrome
4. Hernias
5. Pulmonary hypertension
 A 1,2,3 & 4

 B

2,3,4 & 5

 C

1,2,3 & 5

 D

All are true

Q. 1

Complications of obesity is/are:

1. Venous ulcer
2. Pulmonary embolism
3. Pickwickian syndrome
4. Hernias
5. Pulmonary hypertension
 A 1,2,3 & 4

 B

2,3,4 & 5

 C

1,2,3 & 5

 D

All are true

Ans. D

Explanation:

Clinical presentation of obesity

The morbidly obese patients often presents with chronic weight-related problems such as migraine headaches; back and lower extremity joint pain from degenerative joint disease; venous ulcers; dyspnea on exertion; biliary colic; stress urinary incontinence; dysmenorrhea; infertility; gastroesophageal reflux; and inguinal, umbilical, and incisional hernias.
 
Obesity has a profound effect on overall health and life expectancy. The morbidly obese are predisposed to developing serious weight-related comorbidities, including hypertension, CAD, adult onset DM, sleep apnea and/or obesity hypoventilation syndrome (Pickwickian syndrome), deep venous thrombosis, pulmonary embolism, hypercoagulability, hyperlipidemia, and depression among others.
 
Physiological abnormalities resulting from OSA include hypoxemia, hypercapnia, pulmonary and systemic vasoconstriction, and secondary polycythemia (from recurrent hypoxemia).
These result in an increased risk of ischemic heart disease and cerebrovascular disease.
Right ventricular failure can occur from hypoxic pulmonary vasoconstriction.
 
Obesity is now considered to be the second leading cause of preventable death behind cigarette smoking.
The incidence of comorbidities and mortalities is directly related to the degree of obesity. in a study with 12 year follow up, mortalities rates for those weighing 50% over average weight were doubled. Mortalities and morbidities is largely attributable to the comorbidities of obesity.
 
Ref: Schwartz 9/e, Page 1743.

Q. 2 The following is the commonest site for venous ulcer:
March 2013 (a, e)

 A

Lower third of leg and ankle

 B

Instep of foot

 C

Lower 2/ 3rd of leg

 D

Middle 1/3rd of leg

Q. 2

The following is the commonest site for venous ulcer:
March 2013 (a, e)

 A

Lower third of leg and ankle

 B

Instep of foot

 C

Lower 2/ 3rd of leg

 D

Middle 1/3rd of leg

Ans. A

Explanation:

Ans. A i.e. Lower third of leg and ankle

  • Venous ulcers usually lie just proximal to the medial or lateral malleolus.
    • Venous ulcers are accompanied by lipodermatosclerosis and hemosiderosis (if these are not present then the ulcer is probably not of venous origin).

Quiz In Between



Venous Ulcers

VENOUS ULCERS


VENOUS ULCERS

  • Venous ulcers are situated on the medial side of lower half of the leg above medial malleolus (gaitre’s zone)
  • It is a complication of varicose veins and DVT.

ETIOLOGY-

  1. Fibrin cuff theory-
  • High venous pressure –> pericapillary infiltrate –> fibrin –> fibrosis –> cuffs –> diffusion block –> tissue damage
  1. White cell trapping –> reactive oxygen species –> free radicals –> tissue damage

PATHOGENESIS-

  • Varicose veins or DVT –> Chronic venous hypertension around ankle –> haemosiderin deposition –> eczema –> dermatitis –> lipodermatosclerosis –> fibrosis –> anoxia –> ulceration

CLINICAL FEATURES-

  • Venous ulcer is vertically in shape, solitary, sloping edges and never penetrates deep fascia.
  • Painless
  • Discharge is sloughing with high exudates

INVESTIGATIONS-

  • Duplex ultrasound- IOC for deep and superficial veins
  • Bipedal ascending phelography

TREATMENT-

  • Compression bandaging regiemen

Exam Important

  • Venous ulcers are situated on the medial side of lower half of the leg above medial malleolus (gaitre’s zone)
  • It is a complication of varicose veins and DVT.

CLINICAL FEATURES-

  • Venous ulcer is vertically in shape, solitary, sloping edges and never penetrates deep fascia.
  • Painless
  • Discharge is sloughing with high exudates

INVESTIGATIONS-

  • Duplex ultrasound- IOC for deep and superficial veins
  • Bipedal ascending phelography
Don’t Forget to Solve all the previous Year Question asked on VENOUS ULCERS

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Shigella : Clinical Findings, Pathogenesis, Lab Diagnosis and Treatment

Shigella : Clinical Findings, Pathogenesis, Lab Diagnosis and Treatment

Q. 1

A previously healthy 11 year old girl develops a gastrointestinal infection with cramping and watery stools. After several days, she begins to pass blood per rectum, and is hospitalized for dehydration. In the hospital, she is noted to have decreasing urine output with rising blood urea nitrogen (BUN). Total blood count reveals anemia and thrombocytopenia, and the peripheral smear is remarkable for fragmented red cells (schistocytes). Infection with which of the following bacterial genera is most likely responsible for this syndrome?

 A

Campylobacter

 B

Clostridium

 C

Salmonella

 D

Shigella

Q. 1

A previously healthy 11 year old girl develops a gastrointestinal infection with cramping and watery stools. After several days, she begins to pass blood per rectum, and is hospitalized for dehydration. In the hospital, she is noted to have decreasing urine output with rising blood urea nitrogen (BUN). Total blood count reveals anemia and thrombocytopenia, and the peripheral smear is remarkable for fragmented red cells (schistocytes). Infection with which of the following bacterial genera is most likely responsible for this syndrome?

 A

Campylobacter

 B

Clostridium

 C

Salmonella

 D

Shigella

Ans. D

Explanation:

This patient has developed hemolytic-uremic syndrome (HUS), a complication of the Shiga toxin or Shiga-like toxin: exotoxins released by Shigella species and the enterohemorrhagic E.coli.
HUS in children usually develops after a gastrointestinal or flu-like illness, and is characterized by bleeding, oliguria, hematuria and microangiopathic hemolytic anemia.
Presumably the Shiga toxin is toxic to the microvasculature, producing microthrombi that consume platelets and RBCs, and may fragment the red cell membrane.
The incorrect choices are all bacteria which may produce an enterocolitis, but do not elicit HUS.
 
A long-term consequence of Campylobacter infection is a reactive arthritis or full-blown Reiter’s syndrome.
 
Clostridial enterocolitis is produced by Clostridium difficile, a normal inhabitant of the gut that produces pseudomembranous colitis when other gut flora are suppressed by treatment with antibiotics.
 
Typhoid fever (produced by Salmonella typhi and S. paratyphi) produces a protracted illness that progresses over several weeks and includes rash and very high fevers, but not HUS.
 
Ref: Ray C.G., Ryan K.J. (2010). Chapter 33. Enterobacteriaceae. In C.G. Ray, K.J. Ryan (Eds), Sherris Medical Microbiology, 5e.

Q. 2

What is drug of choice in dysentery due to shigella?

 A

Doxycycline

 B

Ciprofloxacin

 C

Tetracycline

 D

No antibiotic is recommended

Q. 2

What is drug of choice in dysentery due to shigella?

 A

Doxycycline

 B

Ciprofloxacin

 C

Tetracycline

 D

No antibiotic is recommended

Ans. B

Explanation:

The drug of choice for shigella is ciprofloxacin.

Shigella is usually resistant to ampicillin and cotrimoxazole.

Ref: Park 21st edition, page 204.

Q. 3

All are true about Shigella except – 

 A

Large dose is required for infection

 B

Associated with hemolytic uremic Syndrome

 C

Infective dose for shigella is 10 – 100 bacilli 

 D

Gut pathology is due to toxin

Q. 3

All are true about Shigella except – 

 A

Large dose is required for infection

 B

Associated with hemolytic uremic Syndrome

 C

Infective dose for shigella is 10 – 100 bacilli 

 D

Gut pathology is due to toxin

Ans. A

Explanation:

Ans. is ‘a’ i.e., Large dose is required for infection

SHIGELLOSIS

.Shigella is highly communicable . The infective dose for shigella is less. It can be as low as 10 – 100 bacilli because they survive gastric acidity better than other enterobacteriae.

About option d

.    ” essential process in the pathogenesis is invasion of the mucosal epithelial cells by the organism through phagocytosis. The production of toxin is also of importance for virulence but main factor is invasion of the Epithelial cells of gut by the organism”

.         REMEMBER :

“Non toxigenic mutants can still cause dysentery but not non invasive one”

Quiz In Between


Q. 4

Which of the following statement regarding shigella dysentriae type I is true –

 A

It can lead to haemolytic uremic syndrome

 B

It produces an invasive enterotoxin

 C

It is an facultative aerobe

 D

It is MR negative

Q. 4

Which of the following statement regarding shigella dysentriae type I is true –

 A

It can lead to haemolytic uremic syndrome

 B

It produces an invasive enterotoxin

 C

It is an facultative aerobe

 D

It is MR negative

Ans. A

Explanation:

Ans. is ‘a’ i.e., It can lead to hemolytic uremic syndrome 

  • Hemolytic uremic syndrome occurs with Sh. dysenteriae type 1.
  • Complications are most often seen in infection with Sh dysenteriae type 1 and include :

–    Arthritis                      – Conjuctivitis                       – Intussusception in children

–   Toxic neuritis            – Parotitis                               – HUS

  • Invasive property of shigella does not depend on enterotoxin, It depends on “virulence marker antigen (VMA) encoded by large plasmids.
  • Shigella is aerobe and facultative anaerobe.
  • Shigella is MR positive.

Q. 5

A person returns to Delhi from Bangladesh after 2 days and has diarrhoea. Stool examination shows RBCs in Stool. The likely organism causing is ‑

 A

Enteropathogenic E. Coli

 B

Enterotoxigenic E. Coli

 C

Salmonella typhi

 D

Shigella dysentriae

Q. 5

A person returns to Delhi from Bangladesh after 2 days and has diarrhoea. Stool examination shows RBCs in Stool. The likely organism causing is ‑

 A

Enteropathogenic E. Coli

 B

Enterotoxigenic E. Coli

 C

Salmonella typhi

 D

Shigella dysentriae

Ans. D

Explanation:

Ans. is ‘d’ i.e., Shigella Dysentriae 

. The person is suspected to have traveller’s diarrhoea.

The most common cause of traveller’s diarrhoea is E.coli , but the strains of the E.coli (Enterotoxigenic
& Enteropathogenic) given in the choice do not produce invasive illness i.e presence of blood in stool.

.  It is a feature of Enterohemorrhagic E.coli

.  Now the choice is between Salmonella & Shigella diarrhoea are

. Both these organisms produce invasive disease i.e dysentery or inflammatory diarrhoea . But Shigella & Salmonella can be differentiated on the basis of incubation period.

i)        Shigella                                       (1-2days)

ii)      Salmonella               —)0.         (10-14 days)


Q. 6

Invasive test for shigella is –

 A

Dick’s test

 B

Sereny’s test

 C

Schick’s test

 D

Rabbit ileal loop

Q. 6

Invasive test for shigella is –

 A

Dick’s test

 B

Sereny’s test

 C

Schick’s test

 D

Rabbit ileal loop

Ans. D

Explanation:

Ans. is ‘d’ i.e., Rabbit ileal loop 

.  Enterotoxin (SHET-1 and-2) cause net fluid secretion in ligated ileal loop in vivo and alter electrolyte transport by gut segments in vitro.

. Sereny test is a noninvasive test used for shigella and ETEC —> instillation of a suspension of freshly isolated ETEC or shigella into the eyes of guinea pigs leads to mucopurolent conjuctivitis and severe keratitis.

Quiz In Between


Q. 7

All of the following cause hemolytic uremic syndrome except –

 A

Shigella

 B

Campylobacter

 C

MEC

 D

Vibrio cholera

Q. 7

All of the following cause hemolytic uremic syndrome except –

 A

Shigella

 B

Campylobacter

 C

MEC

 D

Vibrio cholera

Ans. D

Explanation:

Ans. is ‘d’ i.e., Vibrio cholera

Hemolytic uremic syndrome is caused by

 

Enterohemorrhagic E.coli (EHEC) -M.C.

.    Shigella dysenteriae type I

. Campylobacter

•    Salmonella

.    Drugs    -4 Cyclosporine, Clopidogrel and Quinine


Q. 8

Stool examination is required for diagnosis of infection with –

 A

Staph food poisoning

 B

Clostridia

 C

Shigella

 D

All

Q. 8

Stool examination is required for diagnosis of infection with –

 A

Staph food poisoning

 B

Clostridia

 C

Shigella

 D

All

Ans. D

Explanation:

Ans. is ‘a’ i.e., Staph food poisoning; ‘b’ i.e., Clostridia; ‘c’ i.e., Shigella

 All these organisms (option a to d) can cause diarrhea and stool should be examined for diagnosis. Diagnostic approach to infectious diarrhea

.   After the severity of illness is assessed, the most important distinction that the clinician must make is between inflammatory and noninflammatory disease.

.   Examination of a stool sample is an important supplement to the narrative history.

.   Stool should be examined for blood, leukocytes and mucus.

.   Fecal lactoferrin is a marker of fecal leukocytes and can be detected by later agglutination or ELISA. For options ‘e’

“Since pinworm (E. vermicularis) eggs not usually released in the bowel, the diagnosis cannot be made by looking for eggs in the feces”.


Q. 9

In shigella dysentry associated hemolytic uremic syndrome, the false statement is ‑

 A

Leucocytosis

 B

Neurological abnormalities

 C

Hepatic failure

 D

Thrombotic angiopathy

Q. 9

In shigella dysentry associated hemolytic uremic syndrome, the false statement is ‑

 A

Leucocytosis

 B

Neurological abnormalities

 C

Hepatic failure

 D

Thrombotic angiopathy

Ans. C

Explanation:

Ans. is ‘c’ i.e., Hepatic failure

o Hepatic failure does not occur in HUS.

Laboratory findings of HUS

o Thrombocytopenia                                                                                     o Leukocytosis

o ARF r BUN and creatinine with oliguria                                                           o Microscopic hematuria

o Peripheral smear Helmet cells, burr cells, fragmental RBCs (Schistocytes).         o Proteinuria

o Hemoglobinuria with hemosiderinuria                                                         o Normal PT and APTT Option ‘b’ requires some explanation here ‑

Though neurological manifestations may occur in HUS, these are not common and this feature differentiated HUS from TTP. In TTP neurological symptom is one of the clinical criteria for diagnosis.

Quiz In Between


Q. 10

Shigella associated hemolytic uramic syndrome is associated with all of the following except‑

 A

Hyperkalemia

 B

Thrombocytopenia

 C

Neurological symptom

 D

Renal micro thrombi

Q. 10

Shigella associated hemolytic uramic syndrome is associated with all of the following except‑

 A

Hyperkalemia

 B

Thrombocytopenia

 C

Neurological symptom

 D

Renal micro thrombi

Ans. A

Explanation:

Answer is A or None (Hyperkalemia or None)

Hyperkalemia is the single best answer of exclusion.

HUS may occur with Shigella Dysentriae type I.

Clinical features in HUS due to shigella as mentioned in (Harrison 14th/959) include :

  • Oliguria progressing to anuria and renal.failuree
  • Drop in hematocrit progressing to severe anemia and CHFQ
  • CNS abnormalities include – encephalopathic symptoms

–  seizures

altered consciousness – bizzare posturing

• Laboratory : – Profound hyponatremia Q and severe hypoglycemia° may be seen

– Leukamoid reactions with increased leucocyte counts Qmay be seen

ThrombocytopeniaQ is common cla

– Although one might argue that hyperkalemia may as well be a feature of HUS on account of renal failure, 1 have excluded it because all other options have been mentioned directly in the standard Harrison text.


Q. 11

Rash is not caused by ‑

 A

Salmonella

 B

Shigella

 C

Meningococci

 D

Staphylococcus

Q. 11

Rash is not caused by ‑

 A

Salmonella

 B

Shigella

 C

Meningococci

 D

Staphylococcus

Ans. B

Explanation:

Ans. is ‘b’ i.e., Shigella

Salmonella (typhoid) and meningococci cause morbiliform rash. Staphylococcus causes scarlentiform rash in TS S and SSSS.

Infections causing Exanthems (acute generalized rash)

Morbilliform

  • Viral : Measles (rubeola), rubella, erythema infectiosum, EBV, CMV, adenovirus, echovirus, early HIV, coxasackie virus.
  • Bacterial : Typhoid, Early secondary syphiis, Early rickettsia, Early meningoccemia.

Scarlentiform

  • Scarlet fever (streptococcus).
  • Toxic shock syndrome.
  • Staphylococcal scalded skin syndrome.

Quiz In Between



Shigella : Clinical Findings, Pathogenesis, Lab Diagnosis and Treatment

Shigella : Clinical Findings, Pathogenesis, Lab Diagnosis and Treatment


 Introduction:

SOURCE:

  • MAN: CASE OR CARRIER

MODE OF SPREAD:

  • CONTAMINATED FINGERS, FOOD, FLIES, FOMITES
  • PERSON TO PERSON TRANSMISSION
  • Gut pathology is due to toxin

INFECTIVE DOSE:

  • 10-100 VIABLE BACILLI
  • HIGHEST CONCENTRATION IN STOOL DURING EARLY/ACUTE INFECTION:
  • 103 TO 109 VIABLE BACILLI PER GRAM OF STOOL
PATHOGENESIS

Invasiveness (main):

  • Bacteria invade basolateral surface of colon epithelium
  • Intracellular replication
  • Cell to cell spread with the help of microbial protein
    •  ICS A (ATP-ase)
    •  Host protein cadherin L – CAM.
  • Responsible for late dysentery.
  • Nontoxic mutants can cause dysentery but non-inttasive can’t produce dysentery.

Toxins:

  • Endotoxin 
    • LPS
    • Cause irritation of bowel.

Shigella Dysenteriae-

  • Produces heat labile exotoxin (Shigabacillus exotoxin)

Affect gut and CNS:

  • Show  neurotoxicity on blood vessel of CNS
  • Can lead to miningsmus and coma.
  • Cytotoxicity = Verotoxin I or Shiga like toxin
  • Toxin has two peptide subunit.Toxins produce early, non bloody voluminous diarrhea.
    • A unit (N-glycosidase) of cytotoxin hydrolyzes adenine from specific sites of 60s RNA
    • Inhibits protein synthesis.
    • Contributes to fatal nature.

CLINICAL SYMPTOMS:

  • Shigella  Associated with hemolytic uremic Syndrome
  • Ranges from asymptomatic infection to severe bacillary dysentery
  • Two-stage disease: watery diarrhea changing to dysentery with frequent small stools with blood and mucus, tenesmus, cramps, fever

Early stage:

  • Watery diarrhoea attributed to the enterotoxic activity of Shiga toxin
  • Fever attributed to neurotoxic activity of toxin  
  • Majority of lesion are in distal colon.

COMPLICATIONS

  • Toxic dilatation
  • Colonic perforation
  • Thrombotic thrombocytopenic purpura
  • Reactive arthritis
  • Reiter’s syndrome.
  • HUS
    • Schistocytes are suggestive of hemolytic-uremic syndrome (HUS)

DIAGNOSIS

  • Sampling: fresh stool, mucus flakes and rectal swabs
  • Selenite F broth(0.4%) is used as enrichment and transport media (for 9-12hours)
  • Total blood count reveals anemia and thrombocytopenia, and schistocytes
  • Increase blood urea nitrogen(BUN)
  • Invasive test for shigella is Rabbit ileal loop

TREATMENT:

  • Oral rehydration therapy (No antibiotics) for mild to moderate dehydration.
  • Ciprofloxacin, Fluoroquinol,  Azithromycin, Pivmecillinam, Ceftriaxone
  • Preventing infected individuals from handling food
  • DOC for multiresistant Nalidixic acid.

Exam Important

 Introduction:

  • PERSON TO PERSON TRANSMISSION
  • Gut pathology is due to toxin

INFECTIVE DOSE:

  •  10-100 VIABLE BACILLI

Toxins:

  • Endotoxin 
    • LPS
    • Cause irritation of bowel.

Shigella Dysenteriae-

  • Produces heat labile exotoxin (Shiga bacillus exotoxin)

Affect gut and CNS:

  • Show  neurotoxicity on blood vessel of CNS
  • Cytotoxicity = Verotoxin I or Shiga like toxin
  • Toxins produce early, non bloody voluminous diarrhea.

CLINICAL SYMPTOMS:

  • Shigella  Associated with hemolytic uremic Syndrome
  • Ranges from asymptomatic infection to severe bacillary dysentery
  • Two-stage disease: watery diarrhea changing to dysentery with frequent small stools with blood and mucus, tenesmus, cramps, fever

Early stage:

  • Watery diarrhoea attributed to the enterotoxic activity of Shiga toxin
  • Fever attributed to neurotoxic activity of toxin  
  • Majority of lesion are in distal colon.

COMPLICATIONS

  • HUS
    • Schistocytes are suggestive of hemolytic-uremic syndrome (HUS)

DIAGNOSIS

  • Sampling: fresh stool, mucus flakes and rectal swabs
  • Selenite F broth(0.4%) is used as enrichment and transport media (for 9-12hours)
  • Total blood count reveals anemia and thrombocytopenia, and schistocytes
  • Increase blood urea nitrogen(BUN)
  • Invasive test for shigella is Rabbit ileal loop

TREATMENT:

  • Oral rehydration therapy (No antibiotics) for mild to moderate dehydration.
  • Ciprofloxacin, Fluoroquinol,  Azithromycin, Pivmecillinam, Ceftriaxone
  • DOC for multiresistant Nalidixic acid.

 

Don’t Forget to Solve all the previous Year Question asked on Shigella : Clinical Findings, Pathogenesis, Lab Diagnosis and Treatment

Module Below Start Quiz

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